Testing the Addition of Herceptin Hylecta or Phesgo to the Usual Chemotherapy for HER2 Positive Endometrial Serous Carcinoma or Carcinosarcoma
- Conditions
- Endometrial CarcinomaEndometrial Undifferentiated CarcinomaUterine Corpus CarcinosarcomaEndometrial Clear Cell AdenocarcinomaEndometrial Dedifferentiated CarcinomaEndometrial Endometrioid AdenocarcinomaEndometrial Mixed Cell AdenocarcinomaEndometrial Serous Adenocarcinoma
- Interventions
- Procedure: Biospecimen CollectionProcedure: Computed TomographyProcedure: Echocardiography TestRadiation: High-Dose-Rate Vaginal Cuff BrachytherapyProcedure: Multigated Acquisition ScanDrug: Hyaluronidase-zzxf/Pertuzumab/TrastuzumabOther: Survey Administration
- Registration Number
- NCT05256225
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase III trial tests whether adding trastuzumab and hyaluronidase-oysk (Herceptin Hylecta \[TM\]) or pertuzumab, trastuzumab and hyaluronidase-zzxf (Phesgo \[TM\]) to the usual chemotherapy (paclitaxel and carboplatin) works to shrink tumors in patients with HER2 positive endometrial cancer. Trastuzumab and pertuzumab are monoclonal antibodies and forms of targeted therapy that attach to specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors. When trastuzumab or pertuzumab attach to HER2 receptors, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Hyaluronidase is an endoglycosidase. It helps to keep pertuzumab and trastuzumab in the body longer, so that these medications will have a greater effect. Hyaluronidase also allows trastuzumab and trastuzumab/pertuzumab to be given by injection under the skin and shortens their administration time compared to trastuzumab or pertuzumab alone. Paclitaxel is a taxane and in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Giving Herceptin Hylecta or Phesgo in combination with paclitaxel and carboplatin may shrink the tumor and prevent the cancer from coming back in patients with HER2 positive endometrial cancer.
- Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate the efficacy of trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) and pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO) in combination with paclitaxel/carboplatin in patients with HER2 positive endometrial cancer.
SECONDARY OBJECTIVES:
I. To evaluate the efficacy of trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) and pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO) in combination with paclitaxel/carboplatin in patients with HER2 positive endometrial cancer.
II. To evaluate the overall response rate (ORR) in patients with measurable disease.
III. To evaluate the duration of objective response in patients with measurable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
IV. To determine the nature, frequency and degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0 for each treatment arm.
V. To compare quality of life (QOL), as measured by Functional Assessment of Cancer Therapy - Endometrial Trial Outcome Index (FACT-En-TOI), in the experimental versus control arms.
VI. To compare patient-reported treatment-associated symptoms (diarrhea and rash) as measured with the Patient Reported Outcomes (PRO) - CTCAE, patient-reported fatigue as measured with the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue short form, and worry concerning side effects of treatment as measured by the item 'bothered by side effect', in the FACT-En TOI, respectively, in the experimental and control arms.
VII. To assess the correlation of HER2 immunohistochemistry (IHC) expression and in situ hybridization (ISH) amplification with clinical outcome and response to HER2 targeted therapies.
EXPLORATORY OBJECTIVE:
I. To explore time to sustained deterioration in quality of life, as measured by a drop in the FACT-En-TOI by 6 or more points lasting for more than one PRO time point, in the experimental and control arms.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease (SD) or partial response (PR) who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician.
ARM II: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and trastuzumab/hyaluronidase-oysk subcutaneously (SC) over 2-5 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician.
MAINTENANCE: Patients receive trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance therapy for up to 3 years from the start of treatment.
ARM III: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and pertuzumab/trastuzumab/hyaluronidase-zzxf SC over 5-8 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician.
MAINTENANCE: Patients receive pertuzumab/trastuzumab/ hyaluronidase-zzxf SC over 5 minutes on day 1. Cycles repeat every 3 weeks for up to 1 year in absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance for up to 3 years from the start of treatment.
Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and computed tomography (CT) throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 360
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Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA-IVB, non-recurrent, chemotherapy (chemo)-naive, HER2-positive endometrial cancer. The following endometrial cancer types are eligible:
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Serous
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Other endometrial cancers (including clear cell, endometrioid, mixed epithelial, dedifferentiated/undifferentiated)
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Carcinosarcoma
- NOTE: Endometrial cancers that are mismatch repair deficient (dMMR) by IHC are not eligible
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Histologic confirmation of the original primary tumor is required. Submission of surgical pathology report (or endometrial biopsy pathology report in patients who never undergo hysterectomy) is required
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Patients must be within 8 weeks of primary surgery (or endometrial biopsy in patients who never undergo hysterectomy) at the time of study registration
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Patients may have measurable disease, non-measurable disease, or no measurable disease. In patients with measurable disease, lesions will be defined and monitored by RECIST v 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be >= 10 mm when measured by CT or magnetic resonance imaging (MRI). Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
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For patients with uterine-confined (stage I) disease, the tumor must be invasive into the myometrium. Any amount of myoinvasion is acceptable for eligibility. Patients with non-invasive disease, endometrial intraepithelial carcinoma alone, or disease confined to a polyp will be excluded
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All patients must have tumors that are HER2 positive as defined by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2018 Breast Cancer guidelines (https://documents.cap.org/documents/algorithim-evaluation-her2.pdf.) IHC and ISH testing will be done locally, at each participating institution and interpreted by local pathologists. In general HER2 positivity is defined as any of the following:
- 3+ immunohistochemistry (IHC),
- 2+ IHC with positive in situ hybridization (ISH) Alternatively, patients could be eligible if next generation sequencing (NGS) demonstrates HER2 (ERBB2) amplification. NGS testing can be performed through any designated labs as per the National Cancer Institute (NCI) MATCH/NCI Combo-MATCH trial (https://ecog-acrin.org/nci-match-eay131-designated-labs).
Pathology report showing results of institutional HER2 testing (or NGS testing results) must be submitted.
Sites must submit all results available (IHC, ISH, and NGS)
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Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
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Age >= 18
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Platelets >= 100,000/mcl (within 14 days prior to registration)
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Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to registration)
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Creatinine =< 1.5 x institutional/laboratory upper limit of normal (ULN) or estimated Glomerular filtration rate (eGFR) >= 50 mL/min using either the Cockcroft-Gault equation, the Modification of Diet in Renal Disease Study, or as reported in the comprehensive metabolic panel/basic metabolic panel (eGFR) (within 14 days prior to registration)
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Total serum bilirubin level =< 1.5 x ULN (patients with known Gilbert's disease who have bilirubin level =< 3 x ULN may be enrolled) (within 14 days prior to registration)
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Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within 14 days prior to registration)
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Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
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Although the uterus will have been removed in the vast majority of patients, for patients of child-bearing potential: negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required. Patients will be considered of non-reproductive potential if they are either:
- Postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age, a high follicle stimulating hormone [FSH] level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient); OR
- Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion at least 6 weeks prior to registration
- Have a congenital or acquired condition that prevents childbearing
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Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
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Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load on suppressive therapy, if indicated
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Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
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Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
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The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
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Prior Therapy:
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Patients must NOT have received prior chemotherapy, biologic therapy, or targeted therapy for treatment of endometrial carcinoma
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Patients must NOT have received prior radiation therapy for treatment of endometrial carcinoma. Prior radiation includes external beam pelvic radiation therapy, external beam extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy
- NOTE: Vaginal brachytherapy for treatment of endometrial cancer is permitted during study treatment. Planned use of vaginal brachytherapy must be declared at time of registration
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Patients may have received prior hormonal therapy for treatment of endometrial carcinoma. All hormonal therapy must be discontinued at least one week prior to registration
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Patients may not have a planned interval cytoreduction or hysterectomy, prior to documentation of progression, after study registration
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Patients may not have planned external beam radiotherapy, prior to documentation of progression, after study registration
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Significant cardiovascular disease including:
- Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg despite antihypertensive medications
- Myocardial infarction or unstable angina within 6 months prior to registration
- New York Heart Association functional classification II, III or IV
- Serious cardiac arrhythmia requiring medication. This does not include asymptomatic, atrial fibrillation with controlled ventricular rate
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Significant lung disease: dyspnea at rest grade 2 or greater (resulting from extensive tumor involvement or other causes), pneumonitis grade 2 or greater, interstitial lung disease grade 2 or greater, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
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Patients with uncontrolled intercurrent illness including, but not limited to: ongoing or active infection (except for uncomplicated urinary tract infection), uncontrolled interstitial lung disease, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements
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Treatment with strong CYP2C8 or CYP3A4 inhibitors or inducers within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to registration
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Women who are unwilling to discontinue nursing
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (paclitaxel, carboplatin) Biospecimen Collection Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm I (paclitaxel, carboplatin) Carboplatin Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm I (paclitaxel, carboplatin) Computed Tomography Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm I (paclitaxel, carboplatin) Echocardiography Test Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm I (paclitaxel, carboplatin) High-Dose-Rate Vaginal Cuff Brachytherapy Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm I (paclitaxel, carboplatin) Multigated Acquisition Scan Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm I (paclitaxel, carboplatin) Paclitaxel Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm II (paclitaxel, carboplatin, Herceptin Hylecta) Biospecimen Collection Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance therapy for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm II (paclitaxel, carboplatin, Herceptin Hylecta) Carboplatin Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance therapy for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm II (paclitaxel, carboplatin, Herceptin Hylecta) Computed Tomography Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance therapy for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm II (paclitaxel, carboplatin, Herceptin Hylecta) Echocardiography Test Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance therapy for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm II (paclitaxel, carboplatin, Herceptin Hylecta) High-Dose-Rate Vaginal Cuff Brachytherapy Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance therapy for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm II (paclitaxel, carboplatin, Herceptin Hylecta) Multigated Acquisition Scan Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance therapy for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm II (paclitaxel, carboplatin, Herceptin Hylecta) Paclitaxel Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance therapy for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm II (paclitaxel, carboplatin, Herceptin Hylecta) Survey Administration Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance therapy for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm II (paclitaxel, carboplatin, Herceptin Hylecta) Trastuzumab/Hyaluronidase-oysk Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance therapy for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm III (paclitaxel, carboplatin, Phesgo) Biospecimen Collection Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and pertuzumab/trastuzumab/hyaluronidase-zzxf SC over 5-8 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive pertuzumab/trastuzumab/ hyaluronidase-zzxf SC over 5 minutes on day 1. Cycles repeat every 3 weeks for up to 1 year in absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm III (paclitaxel, carboplatin, Phesgo) Carboplatin Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and pertuzumab/trastuzumab/hyaluronidase-zzxf SC over 5-8 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive pertuzumab/trastuzumab/ hyaluronidase-zzxf SC over 5 minutes on day 1. Cycles repeat every 3 weeks for up to 1 year in absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm III (paclitaxel, carboplatin, Phesgo) Computed Tomography Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and pertuzumab/trastuzumab/hyaluronidase-zzxf SC over 5-8 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive pertuzumab/trastuzumab/ hyaluronidase-zzxf SC over 5 minutes on day 1. Cycles repeat every 3 weeks for up to 1 year in absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm III (paclitaxel, carboplatin, Phesgo) Echocardiography Test Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and pertuzumab/trastuzumab/hyaluronidase-zzxf SC over 5-8 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive pertuzumab/trastuzumab/ hyaluronidase-zzxf SC over 5 minutes on day 1. Cycles repeat every 3 weeks for up to 1 year in absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm III (paclitaxel, carboplatin, Phesgo) High-Dose-Rate Vaginal Cuff Brachytherapy Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and pertuzumab/trastuzumab/hyaluronidase-zzxf SC over 5-8 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive pertuzumab/trastuzumab/ hyaluronidase-zzxf SC over 5 minutes on day 1. Cycles repeat every 3 weeks for up to 1 year in absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm III (paclitaxel, carboplatin, Phesgo) Hyaluronidase-zzxf/Pertuzumab/Trastuzumab Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and pertuzumab/trastuzumab/hyaluronidase-zzxf SC over 5-8 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive pertuzumab/trastuzumab/ hyaluronidase-zzxf SC over 5 minutes on day 1. Cycles repeat every 3 weeks for up to 1 year in absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm III (paclitaxel, carboplatin, Phesgo) Multigated Acquisition Scan Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and pertuzumab/trastuzumab/hyaluronidase-zzxf SC over 5-8 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive pertuzumab/trastuzumab/ hyaluronidase-zzxf SC over 5 minutes on day 1. Cycles repeat every 3 weeks for up to 1 year in absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm III (paclitaxel, carboplatin, Phesgo) Paclitaxel Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and pertuzumab/trastuzumab/hyaluronidase-zzxf SC over 5-8 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive pertuzumab/trastuzumab/ hyaluronidase-zzxf SC over 5 minutes on day 1. Cycles repeat every 3 weeks for up to 1 year in absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. Arm III (paclitaxel, carboplatin, Phesgo) Survey Administration Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and pertuzumab/trastuzumab/hyaluronidase-zzxf SC over 5-8 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive pertuzumab/trastuzumab/ hyaluronidase-zzxf SC over 5 minutes on day 1. Cycles repeat every 3 weeks for up to 1 year in absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance for up to 3 years from the start of treatment. Patients undergo ECHO or MUGA and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment.
- Primary Outcome Measures
Name Time Method Progression free survival From study entry to time of progression or death, whichever occurs first, or date of last contact if neither progression nor death has occurred, assessed up to 5 years from randomization At the end of Phase 2 analysis, if both experimental arms demonstrate superiority to the reference, the experimental arms will be compared to each other.
Incidence of dose limiting toxicities Up to end of cycle 3 (week 12) A dose limiting toxicity is any treatment-related adverse event requiring permanent discontinuation of the experimental therapy prior to the completion of treatment cycle 3.
Overall survival From study entry to time of death or the date of last contact, assessed up to 5 years from randomization If both experimental arms demonstrate superiority to the reference arm, the experimental arms will be compared to each other.
- Secondary Outcome Measures
Name Time Method Duration of objective response From documentation of either PR or CR until disease progression or death, whichever is observed first, assessed up to 5 years from randomization Treatment group differences in response duration will be graphed using Kaplan-Meier methods and compared using logrank tests, stratified by the minimization factors defined at randomization. The relative hazards of progression or death in each experimental group (vs the reference group) will be estimated using a multivariable proportional hazards regression model specified with main effects for the treatment indicators and covariate adjustments for the stratification factors reported at baseline.
HER2 expression Up to 5 years from randomization Correlation of HER2 immunohistochemistry expression and in situ hybridization amplification with clinical outcome and response to HER2 targeted therapies will be explored.
Incidence of adverse events (AEs) Up to 5 years from randomization The nature, frequency, and degree of toxicity will be tabulated at the System Organ Class and AE-specific term levels using Common Terminology Criteria version 5.0. Each patient will be represented according to the maximum grade observed for each term. Tabulations will show the number and percentage of patients by maximum grade, within the treatment group received, regardless of the randomized treatment assignment.
Quality of life (QoL) Up to 5 years from randomization Measured by Functional Assessment of Cancer Therapy - Endometrial Trial Outcome Index.
Objective response rate (ORR) Within 12 months of initiating maintenance therapy Defined as the binomial proportion of evaluable patients with a best overall response of complete response or partial response (by Response Evaluation Criteria in Solid Tumors 1.1) within 12 months of initiating maintenance therapy. Responses reported by the treating physician will be used for these analyses. The ORR estimates by treatment arm will be supported by their 2-sided, 95% Wilson-Score confidence intervals (Wilson, 1927; Agresti, 1998). The relative odds of response in each experimental group (versus \[vs\] the reference group) will be estimated using a multivariable logistic regression model specified with main effects for the treatment groups and covariate adjustments for the stratification factors reported at baseline.
Trial Locations
- Locations (385)
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Banner University Medical Center - Tucson
🇺🇸Tucson, Arizona, United States
University of Arizona Cancer Center-North Campus
🇺🇸Tucson, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Sutter Auburn Faith Hospital
🇺🇸Auburn, California, United States
Alta Bates Summit Medical Center-Herrick Campus
🇺🇸Berkeley, California, United States
John Muir Medical Center-Concord
🇺🇸Concord, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
City of Hope Seacliff
🇺🇸Huntington Beach, California, United States
City of Hope at Irvine Lennar
🇺🇸Irvine, California, United States
Kaiser Permanente-Irvine
🇺🇸Irvine, California, United States
City of Hope at Long Beach Elm
🇺🇸Long Beach, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Memorial Medical Center
🇺🇸Modesto, California, United States
Palo Alto Medical Foundation-Gynecologic Oncology
🇺🇸Mountain View, California, United States
Saint Joseph Hospital - Orange
🇺🇸Orange, California, United States
Kaiser Permanente - Panorama City
🇺🇸Panorama City, California, United States
Kaiser Permanente-Riverside
🇺🇸Riverside, California, United States
Sutter Roseville Medical Center
🇺🇸Roseville, California, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
California Pacific Medical Center-Pacific Campus
🇺🇸San Francisco, California, United States
Palo Alto Medical Foundation-Santa Cruz
🇺🇸Santa Cruz, California, United States
Palo Alto Medical Foundation-Sunnyvale
🇺🇸Sunnyvale, California, United States
City of Hope Upland
🇺🇸Upland, California, United States
John Muir Medical Center-Walnut Creek
🇺🇸Walnut Creek, California, United States
UCHealth University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
UCHealth - Cherry Creek
🇺🇸Denver, Colorado, United States
Banner North Colorado Medical Center
🇺🇸Greeley, Colorado, United States
UCHealth Highlands Ranch Hospital
🇺🇸Highlands Ranch, Colorado, United States
Banner McKee Medical Center
🇺🇸Loveland, Colorado, United States
Danbury Hospital
🇺🇸Danbury, Connecticut, United States
Smilow Cancer Hospital-Derby Care Center
🇺🇸Derby, Connecticut, United States
Smilow Cancer Hospital Care Center-Fairfield
🇺🇸Fairfield, Connecticut, United States
Smilow Cancer Hospital Care Center at Glastonbury
🇺🇸Glastonbury, Connecticut, United States
Smilow Cancer Hospital Care Center at Greenwich
🇺🇸Greenwich, Connecticut, United States
Smilow Cancer Hospital Care Center - Guilford
🇺🇸Guilford, Connecticut, United States
Smilow Cancer Hospital Care Center at Saint Francis
🇺🇸Hartford, Connecticut, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Yale-New Haven Hospital North Haven Medical Center
🇺🇸North Haven, Connecticut, United States
Norwalk Hospital
🇺🇸Norwalk, Connecticut, United States
Smilow Cancer Hospital Care Center at Long Ridge
🇺🇸Stamford, Connecticut, United States
Smilow Cancer Hospital-Torrington Care Center
🇺🇸Torrington, Connecticut, United States
Smilow Cancer Hospital Care Center-Trumbull
🇺🇸Trumbull, Connecticut, United States
Smilow Cancer Hospital-Waterbury Care Center
🇺🇸Waterbury, Connecticut, United States
Smilow Cancer Hospital Care Center - Waterford
🇺🇸Waterford, Connecticut, United States
Helen F Graham Cancer Center
🇺🇸Newark, Delaware, United States
Medical Oncology Hematology Consultants PA
🇺🇸Newark, Delaware, United States
Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
George Washington University Medical Center
🇺🇸Washington, District of Columbia, United States
Broward Health Medical Center
🇺🇸Fort Lauderdale, Florida, United States
Jupiter Medical Center
🇺🇸Jupiter, Florida, United States
Sarasota Memorial Hospital-Venice
🇺🇸N. Venice, Florida, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Florida Cancer Specialists - Sarasota Downtown
🇺🇸Sarasota, Florida, United States
First Physicians Group-Sarasota
🇺🇸Sarasota, Florida, United States
Sarasota Memorial Hospital
🇺🇸Sarasota, Florida, United States
Florida Cancer Specialists - Venice Pinebrook
🇺🇸Venice, Florida, United States
Grady Health System
🇺🇸Atlanta, Georgia, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Piedmont Hospital
🇺🇸Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
🇺🇸Atlanta, Georgia, United States
Augusta University Medical Center
🇺🇸Augusta, Georgia, United States
Emory Decatur Hospital
🇺🇸Decatur, Georgia, United States
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
🇺🇸Savannah, Georgia, United States
Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸Boise, Idaho, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
Saint Alphonsus Cancer Care Center-Caldwell
🇺🇸Caldwell, Idaho, United States
Kootenai Health - Coeur d'Alene
🇺🇸Coeur d'Alene, Idaho, United States
Saint Luke's Cancer Institute - Fruitland
🇺🇸Fruitland, Idaho, United States
Saint Luke's Cancer Institute - Meridian
🇺🇸Meridian, Idaho, United States
Saint Alphonsus Cancer Care Center-Nampa
🇺🇸Nampa, Idaho, United States
Saint Luke's Cancer Institute - Nampa
🇺🇸Nampa, Idaho, United States
Kootenai Clinic Cancer Services - Post Falls
🇺🇸Post Falls, Idaho, United States
Kootenai Clinic Cancer Services - Sandpoint
🇺🇸Sandpoint, Idaho, United States
Saint Luke's Cancer Institute - Twin Falls
🇺🇸Twin Falls, Idaho, United States
Northwest Community Hospital
🇺🇸Arlington Heights, Illinois, United States
Rush - Copley Medical Center
🇺🇸Aurora, Illinois, United States
Centralia Oncology Clinic
🇺🇸Centralia, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
John H Stroger Jr Hospital of Cook County
🇺🇸Chicago, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Northwestern Medicine Cancer Center Kishwaukee
🇺🇸DeKalb, Illinois, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
NorthShore University HealthSystem-Evanston Hospital
🇺🇸Evanston, Illinois, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸Geneva, Illinois, United States
NorthShore University HealthSystem-Glenbrook Hospital
🇺🇸Glenview, Illinois, United States
Northwestern Medicine Glenview Outpatient Center
🇺🇸Glenview, Illinois, United States
Northwestern Medicine Grayslake Outpatient Center
🇺🇸Grayslake, Illinois, United States
NorthShore University HealthSystem-Highland Park Hospital
🇺🇸Highland Park, Illinois, United States
Sudarshan K Sharma MD Limited-Gynecologic Oncology
🇺🇸Hinsdale, Illinois, United States
Northwestern Medicine Lake Forest Hospital
🇺🇸Lake Forest, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
🇺🇸New Lenox, Illinois, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
Northwestern Medicine Orland Park
🇺🇸Orland Park, Illinois, United States
University of Chicago Medicine-Orland Park
🇺🇸Orland Park, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Springfield Clinic
🇺🇸Springfield, Illinois, United States
Springfield Memorial Hospital
🇺🇸Springfield, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸Warrenville, Illinois, United States
Rush-Copley Healthcare Center
🇺🇸Yorkville, Illinois, United States
IU Health North Hospital
🇺🇸Carmel, Indiana, United States
Northwest Cancer Center - Main Campus
🇺🇸Crown Point, Indiana, United States
Northwest Oncology LLC
🇺🇸Dyer, Indiana, United States
Goshen Center for Cancer Care
🇺🇸Goshen, Indiana, United States
Northwest Cancer Center - Hobart
🇺🇸Hobart, Indiana, United States
Saint Mary Medical Center
🇺🇸Hobart, Indiana, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Franciscan Health Indianapolis
🇺🇸Indianapolis, Indiana, United States
Ascension Saint Vincent Indianapolis Hospital
🇺🇸Indianapolis, Indiana, United States
Saint Catherine Hospital
🇺🇸Indianapolis, Indiana, United States
Franciscan Saint Elizabeth Health - Lafayette East
🇺🇸Lafayette, Indiana, United States
Franciscan Health Mooresville
🇺🇸Mooresville, Indiana, United States
The Community Hospital
🇺🇸Munster, Indiana, United States
Women's Diagnostic Center - Munster
🇺🇸Munster, Indiana, United States
Memorial Hospital of South Bend
🇺🇸South Bend, Indiana, United States
Northwest Cancer Center - Valparaiso
🇺🇸Valparaiso, Indiana, United States
Mary Greeley Medical Center
🇺🇸Ames, Iowa, United States
McFarland Clinic - Ames
🇺🇸Ames, Iowa, United States
McFarland Clinic - Boone
🇺🇸Boone, Iowa, United States
Heartland Oncology and Hematology LLP
🇺🇸Council Bluffs, Iowa, United States
Nebraska Cancer Specialists/Oncology Hematology West PC - MEJ
🇺🇸Council Bluffs, Iowa, United States
McFarland Clinic - Trinity Cancer Center
🇺🇸Fort Dodge, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
McFarland Clinic - Jefferson
🇺🇸Jefferson, Iowa, United States
McFarland Clinic - Marshalltown
🇺🇸Marshalltown, Iowa, United States
Saint Elizabeth Healthcare Edgewood
🇺🇸Edgewood, Kentucky, United States
Baptist Health Lexington
🇺🇸Lexington, Kentucky, United States
Baptist Health Louisville
🇺🇸Louisville, Kentucky, United States
LSU Health Baton Rouge-North Clinic
🇺🇸Baton Rouge, Louisiana, United States
Our Lady of the Lake Physician Group
🇺🇸Baton Rouge, Louisiana, United States
Our Lady of the Lake Medical Oncology
🇺🇸Baton Rouge, Louisiana, United States
Ochsner Hematology Oncology North Shore - Covington (West Region)
🇺🇸Covington, Louisiana, United States
East Jefferson General Hospital
🇺🇸Metairie, Louisiana, United States
University Medical Center New Orleans
🇺🇸New Orleans, Louisiana, United States
Ochsner Baptist Medical Center
🇺🇸New Orleans, Louisiana, United States
Ochsner Medical Center Jefferson
🇺🇸New Orleans, Louisiana, United States
Harold Alfond Center for Cancer Care
🇺🇸Augusta, Maine, United States
MaineHealth Maine Medical Center- Scarborough
🇺🇸Scarborough, Maine, United States
Greater Baltimore Medical Center
🇺🇸Baltimore, Maryland, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
MedStar Franklin Square Medical Center/Weinberg Cancer Institute
🇺🇸Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
William E Kahlert Regional Cancer Center/Sinai Hospital
🇺🇸Westminster, Maryland, United States
Baystate Medical Center
🇺🇸Springfield, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
🇺🇸Brighton, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
🇺🇸Canton, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
🇺🇸Chelsea, Michigan, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Weisberg Cancer Treatment Center
🇺🇸Farmington Hills, Michigan, United States
Corewell Health Farmington Hills Hospital
🇺🇸Farmington Hills, Michigan, United States
Cancer Hematology Centers - Flint
🇺🇸Flint, Michigan, United States
Genesee Hematology Oncology PC
🇺🇸Flint, Michigan, United States
Genesys Hurley Cancer Institute
🇺🇸Flint, Michigan, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
🇺🇸Grand Rapids, Michigan, United States
Trinity Health Grand Rapids Hospital
🇺🇸Grand Rapids, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Ascension Borgess Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
🇺🇸Livonia, Michigan, United States
Trinity Health Muskegon Hospital
🇺🇸Muskegon, Michigan, United States
Corewell Health Lakeland Hospitals - Niles Hospital
🇺🇸Niles, Michigan, United States
Cancer and Hematology Centers of Western Michigan - Norton Shores
🇺🇸Norton Shores, Michigan, United States
Trinity Health Saint Joseph Mercy Oakland Hospital
🇺🇸Pontiac, Michigan, United States
Corewell Health Reed City Hospital
🇺🇸Reed City, Michigan, United States
Corewell Health William Beaumont University Hospital
🇺🇸Royal Oak, Michigan, United States
MyMichigan Medical Center Saginaw
🇺🇸Saginaw, Michigan, United States
Oncology Hematology Associates of Saginaw Valley PC
🇺🇸Saginaw, Michigan, United States
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
🇺🇸Saint Joseph, Michigan, United States
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
🇺🇸Saint Joseph, Michigan, United States
MyMichigan Medical Center Tawas
🇺🇸Tawas City, Michigan, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
Corewell Health Beaumont Troy Hospital
🇺🇸Troy, Michigan, United States
Saint Mary's Oncology/Hematology Associates of West Branch
🇺🇸West Branch, Michigan, United States
University of Michigan Health - West
🇺🇸Wyoming, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
🇺🇸Ypsilanti, Michigan, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota/Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Minnesota Oncology Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
MU Health - University Hospital/Ellis Fischel Cancer Center
🇺🇸Columbia, Missouri, United States
Phelps Health Delbert Day Cancer Institute
🇺🇸Rolla, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital South
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
Community Hospital of Anaconda
🇺🇸Anaconda, Montana, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
ProMedica Flower Hospital
🇺🇸Sylvania, Ohio, United States
Saint Vincent Frontier Cancer Center
🇺🇸Billings, Montana, United States
Intermountain Health West End Clinic
🇺🇸Billings, Montana, United States
Bozeman Health Deaconess Hospital
🇺🇸Bozeman, Montana, United States
Benefis Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Logan Health Medical Center
🇺🇸Kalispell, Montana, United States
Saint Patrick Hospital - Community Hospital
🇺🇸Missoula, Montana, United States
Community Medical Center
🇺🇸Missoula, Montana, United States
Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
🇺🇸Omaha, Nebraska, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Alegent Health Bergan Mercy Medical Center
🇺🇸Omaha, Nebraska, United States
OptumCare Cancer Care at Seven Hills
🇺🇸Henderson, Nevada, United States
OptumCare Cancer Care at Charleston
🇺🇸Las Vegas, Nevada, United States
Women's Cancer Center of Nevada
🇺🇸Las Vegas, Nevada, United States
OptumCare Cancer Care at Fort Apache
🇺🇸Las Vegas, Nevada, United States
Memorial Sloan Kettering Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Cooper Hospital University Medical Center
🇺🇸Camden, New Jersey, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Monmouth Medical Center Southern Campus
🇺🇸Lakewood, New Jersey, United States
Saint Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
Monmouth Medical Center
🇺🇸Long Branch, New Jersey, United States
Memorial Sloan Kettering Monmouth
🇺🇸Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
🇺🇸Montvale, New Jersey, United States
Virtua Samson Cancer Center
🇺🇸Moorestown, New Jersey, United States
Jersey Shore Medical Center
🇺🇸Neptune, New Jersey, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Riverview Medical Center/Booker Cancer Center
🇺🇸Red Bank, New Jersey, United States
Sidney Kimmel Cancer Center Washington Township
🇺🇸Sewell, New Jersey, United States
Robert Wood Johnson University Hospital Somerset
🇺🇸Somerville, New Jersey, United States
Virtua Voorhees
🇺🇸Voorhees, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Presbyterian Kaseman Hospital
🇺🇸Albuquerque, New Mexico, United States
Presbyterian Rust Medical Center/Jorgensen Cancer Center
🇺🇸Rio Rancho, New Mexico, United States
Women's Cancer Care Associates LLC
🇺🇸Albany, New York, United States
Memorial Sloan Kettering Commack
🇺🇸Commack, New York, United States
Memorial Sloan Kettering Westchester
🇺🇸Harrison, New York, United States
NYU Langone Hospital - Long Island
🇺🇸Mineola, New York, United States
Mount Sinai Chelsea
🇺🇸New York, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸New York, New York, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Memorial Sloan Kettering Nassau
🇺🇸Uniondale, New York, United States
Duke Cancer Center Cary
🇺🇸Cary, North Carolina, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
ECU Health Medical Center
🇺🇸Greenville, North Carolina, United States
Hayworth Cancer Center
🇺🇸High Point, North Carolina, United States
Duke Women's Cancer Care Raleigh
🇺🇸Raleigh, North Carolina, United States
Novant Health New Hanover Regional Medical Center
🇺🇸Wilmington, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Sanford Roger Maris Cancer Center
🇺🇸Fargo, North Dakota, United States
UHHS-Chagrin Highlands Medical Center
🇺🇸Beachwood, Ohio, United States
Strecker Cancer Center-Belpre
🇺🇸Belpre, Ohio, United States
Aultman Health Foundation
🇺🇸Canton, Ohio, United States
Miami Valley Hospital South
🇺🇸Centerville, Ohio, United States
Geauga Hospital
🇺🇸Chardon, Ohio, United States
Adena Regional Medical Center
🇺🇸Chillicothe, Ohio, United States
Good Samaritan Hospital - Cincinnati
🇺🇸Cincinnati, Ohio, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Mount Carmel East Hospital
🇺🇸Columbus, Ohio, United States
Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
The Mark H Zangmeister Center
🇺🇸Columbus, Ohio, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Miami Valley Hospital North
🇺🇸Dayton, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸Franklin, Ohio, United States
Miami Valley Cancer Care and Infusion
🇺🇸Greenville, Ohio, United States
Mount Carmel Grove City Hospital
🇺🇸Grove City, Ohio, United States
Fairfield Medical Center
🇺🇸Lancaster, Ohio, United States
Saint Rita's Medical Center
🇺🇸Lima, Ohio, United States
Marietta Memorial Hospital
🇺🇸Marietta, Ohio, United States
Memorial Hospital
🇺🇸Marysville, Ohio, United States
UH Seidman Cancer Center at Lake Health Mentor Campus
🇺🇸Mentor, Ohio, United States
Knox Community Hospital
🇺🇸Mount Vernon, Ohio, United States
Licking Memorial Hospital
🇺🇸Newark, Ohio, United States
Mercy Health - Perrysburg Hospital
🇺🇸Perrysburg, Ohio, United States
Southern Ohio Medical Center
🇺🇸Portsmouth, Ohio, United States
Springfield Regional Cancer Center
🇺🇸Springfield, Ohio, United States
Springfield Regional Medical Center
🇺🇸Springfield, Ohio, United States
Mercy Health - Saint Vincent Hospital
🇺🇸Toledo, Ohio, United States
Mercy Health - Saint Anne Hospital
🇺🇸Toledo, Ohio, United States
Upper Valley Medical Center
🇺🇸Troy, Ohio, United States
Saint Ann's Hospital
🇺🇸Westerville, Ohio, United States
UH Seidman Cancer Center at Saint John Medical Center
🇺🇸Westlake, Ohio, United States
Genesis Healthcare System Cancer Care Center
🇺🇸Zanesville, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Mercy Hospital Oklahoma City
🇺🇸Oklahoma City, Oklahoma, United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
🇺🇸Tulsa, Oklahoma, United States
Providence Cancer Institute Clackamas Clinic
🇺🇸Clackamas, Oregon, United States
Providence Newberg Medical Center
🇺🇸Newberg, Oregon, United States
Saint Alphonsus Cancer Care Center-Ontario
🇺🇸Ontario, Oregon, United States
Legacy Good Samaritan Hospital and Medical Center
🇺🇸Portland, Oregon, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Legacy Meridian Park Hospital
🇺🇸Tualatin, Oregon, United States
Lehigh Valley Hospital-Cedar Crest
🇺🇸Allentown, Pennsylvania, United States
Saint Luke's Cancer Center - Allentown
🇺🇸Allentown, Pennsylvania, United States
Saint Luke's University Hospital-Bethlehem Campus
🇺🇸Bethlehem, Pennsylvania, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
Bryn Mawr Hospital
🇺🇸Bryn Mawr, Pennsylvania, United States
Pocono Medical Center
🇺🇸East Stroudsburg, Pennsylvania, United States
Saint Luke's Hospital-Anderson Campus
🇺🇸Easton, Pennsylvania, United States
Saint Vincent Hospital
🇺🇸Erie, Pennsylvania, United States
Lehigh Valley Hospital-Hazleton
🇺🇸Hazleton, Pennsylvania, United States
Jefferson Hospital
🇺🇸Jefferson Hills, Pennsylvania, United States
Riddle Memorial Hospital
🇺🇸Media, Pennsylvania, United States
Forbes Hospital
🇺🇸Monroeville, Pennsylvania, United States
Paoli Memorial Hospital
🇺🇸Paoli, Pennsylvania, United States
Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
West Penn Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Saint Luke's Hospital - Upper Bucks Campus
🇺🇸Quakertown, Pennsylvania, United States
Chester County Hospital
🇺🇸West Chester, Pennsylvania, United States
Wexford Health and Wellness Pavilion
🇺🇸Wexford, Pennsylvania, United States
Asplundh Cancer Pavilion
🇺🇸Willow Grove, Pennsylvania, United States
Lankenau Medical Center
🇺🇸Wynnewood, Pennsylvania, United States
Women and Infants Hospital
🇺🇸Providence, Rhode Island, United States
Smilow Cancer Hospital Care Center - Westerly
🇺🇸Westerly, Rhode Island, United States
Saint Joseph's/Candler - Bluffton Campus
🇺🇸Bluffton, South Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Avera Cancer Institute-Aberdeen
🇺🇸Aberdeen, South Dakota, United States
Rapid City Regional Hospital
🇺🇸Rapid City, South Dakota, United States
Sanford Cancer Center Oncology Clinic
🇺🇸Sioux Falls, South Dakota, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
The West Clinic - Wolf River
🇺🇸Germantown, Tennessee, United States
Dell Seton Medical Center at The University of Texas
🇺🇸Austin, Texas, United States
University of Texas at Austin
🇺🇸Austin, Texas, United States
Parkland Memorial Hospital
🇺🇸Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
Tarrant County Hospital District/JPS Health Network
🇺🇸Fort Worth, Texas, United States
UT Southwestern/Simmons Cancer Center-Fort Worth
🇺🇸Fort Worth, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Memorial Hermann Texas Medical Center
🇺🇸Houston, Texas, United States
Methodist Willowbrook Hospital
🇺🇸Houston, Texas, United States
Houston Methodist West Hospital
🇺🇸Houston, Texas, United States
Houston Methodist Saint John Hospital
🇺🇸Nassau Bay, Texas, United States
UT Southwestern Clinical Center at Richardson/Plano
🇺🇸Richardson, Texas, United States
Houston Methodist Sugar Land Hospital
🇺🇸Sugar Land, Texas, United States
Houston Methodist The Woodlands Hospital
🇺🇸The Woodlands, Texas, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
South Jordan Health Center
🇺🇸South Jordan, Utah, United States
Henrico Doctor's Hospital
🇺🇸Richmond, Virginia, United States
VCU Massey Cancer Center at Stony Point
🇺🇸Richmond, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Carilion Roanoke Memorial Hospital
🇺🇸Roanoke, Virginia, United States
Swedish Cancer Institute-Edmonds
🇺🇸Edmonds, Washington, United States
Swedish Medical Center-First Hill
🇺🇸Seattle, Washington, United States
Legacy Salmon Creek Hospital
🇺🇸Vancouver, Washington, United States
West Virginia University Charleston Division
🇺🇸Charleston, West Virginia, United States
West Virginia University Healthcare
🇺🇸Morgantown, West Virginia, United States
Marshfield Medical Center-EC Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
Saint Vincent Hospital Cancer Center Green Bay
🇺🇸Green Bay, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
🇺🇸Green Bay, Wisconsin, United States
Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
🇺🇸Madison, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - University Hospital
🇺🇸Madison, Wisconsin, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Marshfield Medical Center - Minocqua
🇺🇸Minocqua, Wisconsin, United States
ProHealth D N Greenwald Center
🇺🇸Mukwonago, Wisconsin, United States
Cancer Center of Western Wisconsin
🇺🇸New Richmond, Wisconsin, United States
ProHealth Oconomowoc Memorial Hospital
🇺🇸Oconomowoc, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Oconto Falls
🇺🇸Oconto Falls, Wisconsin, United States
Marshfield Medical Center-Rice Lake
🇺🇸Rice Lake, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Sheboygan
🇺🇸Sheboygan, Wisconsin, United States
Sheboygan Physicians Group
🇺🇸Sheboygan, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Sturgeon Bay
🇺🇸Sturgeon Bay, Wisconsin, United States
UW Cancer Center at ProHealth Care
🇺🇸Waukesha, Wisconsin, United States
Marshfield Medical Center - Weston
🇺🇸Weston, Wisconsin, United States
Centro Comprensivo de Cancer de UPR
🇵🇷San Juan, Puerto Rico