Paclitaxel, Carboplatin, and Bevacizumab or Paclitaxel, Carboplatin, and Temsirolimus or Ixabepilone, Carboplatin, and Bevacizumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer

Phase 2

Active, not recruiting

• Conditions: Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Malignant Uterine Corpus Neoplasm; Stage IIIA Uterine Corpus Carcinoma or Carcinosarcoma by AJCC v7 Stage; Stage IIIB Uterine Corpus Carcinoma or Carcinosarcoma by AJCC v7 Stage; Stage IIIC Uterine Corpus Carcinoma or Carcinosarcoma by AJCC v7 Stage; Stage IVA Uterine Corpus Carcinoma or Carcinosarcoma by AJCC v7 Stage; Stage IVB Uterine Corpus Carcinoma or Carcinosarcoma by AJCC v7 Stage
• Interventions: Biological: Bevacizumab; Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Ixabepilone; Drug: Paclitaxel; Drug: Temsirolimus

• Registration Number: NCT00977574
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

This randomized phase II trial studies paclitaxel, carboplatin, and bevacizumab or paclitaxel, carboplatin, and temsirolimus or ixabepilone, carboplatin, and bevacizumab to see how well they work in treating patients with stage III, stage IV, or recurrent endometrial cancer. Drugs used in chemotherapy, such as paclitaxel, carboplatin, and ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known which treatment regimen is most effective in treating patients with endometrial cancer.

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the hazard of progression or death of each of the three arms relative to that of historical controls in patients with advanced or recurrent endometrial cancer.

SECONDARY OBJECTIVES:

I. To determine the nature, frequency, and maximum degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v)3.0 for each of the three arms.

II. To estimate the distribution of the duration of overall survival for each of the three arms.

III. To estimate the proportion of patients with measurable disease who have confirmed objective tumor responses by treatment.

TERTIARY OBJECTIVES:

I. Explore the associations between select biomarkers and progression-free survival as well as secondary measures of clinical outcome (overall survival, tumor response, or disease status if possible) in the context of histologic cell type and treatment.

IA. Somatic mutations in phosphatase and tensin homolog (PTEN)/ phosphoinositide-3-kinase (PI3K) and RAS pathway members by Sequenom mutational profiling and targeted sequencing of candidate genes.

IB. Microsatellite instability by analysis of five National Cancer Institute consensus microsatellite markers (BAT25, BAT26, D2S2123, D5S346, and D17S250) using the Applied Biosystems (ABI) Prism 3100 Genetic Analyzer.

IC. Copy number alterations (gains or losses) by array comparative genomic hybridization (aCGH).

ID. Tumor expression of PTEN and class III beta-tubulin using immunohistochemistry.

IE. Concentration of vascular endothelial growth factor (VEGF) in pre-cycle 1 plasma using an enzyme-linked immunosorbent assay.

II. Explore the relationship among the various biomarkers by histologic subtype and treatment.

III. Explore which combination of biomarkers and clinical covariates optimally predicts responsiveness and resistance to the three treatment arms.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours, carboplatin IV over 30 minutes, and bevacizumab\* IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: \*Patients undergoing treatment post-surgery (=\< 12 weeks) receive bevacizumab beginning on course 2.

ARM II: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus\* IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive temsirolimus IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: \*Patients undergoing treatment post-surgery (=\< 12 weeks) receive temsirolimus beginning on course 2.

ARM III: Patients receive ixabepilone IV over 1 hour, carboplatin IV over 30 minutes, and bevacizumab\* IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: \*Patients undergoing treatment post-surgery (=\< 12 weeks) receive bevacizumab beginning on course 2.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study Timeline

• Study First Submitted: 2009-09-12
• Study First Submitted QC: 2009-09-12
• Study Start: 2009-09-14
• Study First Posted: 2009-09-15
• Primary Completion: 2015-01-31
• Results First Submitted: 2017-10-20
• Results First Submitted QC: 2018-01-29
• Results First Posted: 2018-02-27
• Status Verified: 2025-03
• Last Update Submitted: 2025-04-02
• Last Update Posted: 2025-04-20
• Study Completion: 2026-03-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 349

Inclusion Criteria

• Patients must have measurable stage III, measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial carcinoma

  • Histologic confirmation of the original primary tumor is required; patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma

• Measurable disease is defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 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 computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI

• Patients must have Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2

• Patients must not be eligible for a higher priority GOG protocol, if one exists; in general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population

• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl equivalent to Common Terminology Criteria (CTCAE v3.0) grade 1

• Platelets greater than or equal to 100,000/mcl

• Creatinine less than or equal to 1.5 times institutional upper limit normal (ULN), CTCAE v3.0 grade 1

• Bilirubin less than or equal to 1.5 x ULN (CTCAE v3.0 grade 1)

• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)

• Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)

• Urine protein creatinine (UPC) ratio must be < 1.0 gram (gm); if UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended (24-hour urine protein level must be < 1000 mg for patient enrollment)

  • UPC ratio of spot urine is an estimation of the 24 urine protein excretion

    • A UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm

• Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) =< 1.5 x ULN

• Fasting cholesterol less than 300 mg/dL (CTCAE v3.0 grade 1)

• Fasting triglycerides =< 2.5 x ULN (CTCAE v3.0 grade 1)

• Patients must NOT have received prior chemotherapy or targeted therapy, including chemotherapy used for radiation sensitization for treatment of endometrial carcinoma

• Patients must NOT have received prior therapy with bevacizumab or other VEGF pathway targeted therapy; patients must NOT have received prior therapy with temsirolimus, everolimus, ridaforolimus, sirolimus, or any other PI3K/ v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycins (mTor) pathway targeted therapy

• Patients may have receive prior radiation therapy for treatment of endometrial carcinoma; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy; all radiation therapy must be completed at least 4 weeks prior to the first date of study therapy; the prior radiation field, radiation dose, number of fractions and prior radiation start and stop dates must be provided on the Fast Fact Sheet (FFS) at registration

• Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least one week prior to the first date of study therapy

• Patients must have signed an approved informed consent and authorization permitting release of personal health information

Exclusion Criteria

• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, and other specific malignancies as noted below, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy

• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease

• Patients who have received prior chemotherapy for any abdominal or pelvic tumor within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease

• Patients with serious, non-healing wound, ulcer, or bone fracture; this includes history of abdominal/pelvic fistula, gastrointestinal perforation or intra-abdominal abscess within 3 months prior to the first date of study therapy; patients with underlying lesions that caused the fistula or perforation in the past that have not been corrected

• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels

• Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy or any brain metastases

• Patients with clinically significant cardiovascular disease; this includes:

  • Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg
  • Myocardial infarction or unstable angina within 6 months of the first date of study therapy
  • New York Heart Association (NYHA) class II or greater congestive heart failure
  • History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)
  • CTCAE grade 2 or greater peripheral vascular disease.
  • History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of study therapy.
  • Aortic aneurysm and/or history of aortic dissection

• Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies

• Patients undergoing invasive procedures as defined below:

  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of bevacizumab or temsirolimus therapy
  • Major surgical procedure anticipated during the course of the study.
  • Minor surgical procedures, fine needle aspirates, or core biopsies within 7 days prior to the first date of study therapy

• Patients with known prior history of interstitial pneumonitis

• Patients with CTCAE v. 3, grade 2 or greater hypoxemia

• Patients with CTCAE v. 3, grade 2 or greater dyspnea

• Patients must not have uncontrolled diabetes, and must not have baseline hemoglobin A1C (HgbA1C) > 8

• Patients with peripheral neuropathy > CTCAE v.3, grade 1

• Patients who are pregnant or nursing

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (paclitaxel, carboplatin, bevacizumab)	Bevacizumab	Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm I (paclitaxel, carboplatin, bevacizumab)	Carboplatin	Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm I (paclitaxel, carboplatin, bevacizumab)	Laboratory Biomarker Analysis	Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm I (paclitaxel, carboplatin, bevacizumab)	Paclitaxel	Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm II (paclitaxel, carboplatin, temsirolimus)	Carboplatin	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm II (paclitaxel, carboplatin, temsirolimus)	Laboratory Biomarker Analysis	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm II (paclitaxel, carboplatin, temsirolimus)	Paclitaxel	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm II (paclitaxel, carboplatin, temsirolimus)	Temsirolimus	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm III (ixabepilone, carboplatin, bevacizumab)	Bevacizumab	Patients receive ixabepilone IV over 1 hour, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm III (ixabepilone, carboplatin, bevacizumab)	Carboplatin	Patients receive ixabepilone IV over 1 hour, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm III (ixabepilone, carboplatin, bevacizumab)	Ixabepilone	Patients receive ixabepilone IV over 1 hour, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm III (ixabepilone, carboplatin, bevacizumab)	Laboratory Biomarker Analysis	Patients receive ixabepilone IV over 1 hour, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Progressed or Died by 25 Months From Enrollment	at 25 months	PFS (Progression free survival) is defined as the duration of time from date of study entry to time of progression or death, whichever occurs first. Patients with a status of alive, progression-free are censored at their date of last follow-up. To lessen the potential for bias in the progression evaluation times between treatment arms and historical controls, progression/death times will be grouped over 6 18-week time intervals. Progressions are carried forward to the end of the interval. All progressions or deaths occurring after the 6th 18-week interval are censored at 25 months for this analysis. Study NCT00977574

Secondary Outcome Measures

Name	Time	Method
Frequency and Severity of Toxicity as Assessed by CTCAE v3.0 for Each of the Three Arms.	Median of 10 cycles of treatment plus 30 days
The Median Duration of Overall Survival for Each of the Three Arms.	Time from date of study entry to time of death or the date of last contact, assessed up to 5 years	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
The Proportion of Patients With Measurable Disease Who Have Confirmed Objective Tumor Responses by Treatment.	Imaging was done every 3 cycles and at any other time clinically indicated. Imaging was required every 9 weeks until progression or initiation on non protocol therapy. After 2 years of protocol therapy or follow up, CT scan or MRI was every 3 months	RECIST 1.1 was used to define objective tumor response. A complete response is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. A partial response is defined as At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. There can be no unequivocal progression of non-target lesions and no new lesions. Complete and partial responses are included in the objective tumor response rate. Confirmation of response was not required.

Trial Locations

Locations (230)

Iowa Lutheran Hospital; 🇺🇸 Des Moines, Iowa, United States

Cleveland Clinic Akron General; 🇺🇸 Akron, Ohio, United States

University of Cincinnati Cancer Center-UC Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Case Western Reserve University; 🇺🇸 Cleveland, Ohio, United States

MetroHealth Medical Center; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Cancer Center/Fairview Hospital; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

Riverside Methodist Hospital; 🇺🇸 Columbus, Ohio, United States

Miami Valley Hospital; 🇺🇸 Dayton, Ohio, United States

Kettering Medical Center; 🇺🇸 Kettering, Ohio, United States

Hillcrest Hospital Cancer Center; 🇺🇸 Mayfield Heights, Ohio, United States

UH Seidman Cancer Center at Lake Health Mentor Campus; 🇺🇸 Mentor, Ohio, United States

Saint Joseph's Hospital and Medical Center; 🇺🇸 Phoenix, Arizona, United States

Mayo Clinic in Arizona; 🇺🇸 Scottsdale, Arizona, United States

University of Arizona Cancer Center-North Campus; 🇺🇸 Tucson, Arizona, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center; 🇺🇸 Burbank, California, United States

John Muir Medical Center-Concord; 🇺🇸 Concord, California, United States

UC San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

UCLA / Jonsson Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Palo Alto Medical Foundation-Gynecologic Oncology; 🇺🇸 Mountain View, California, United States

UC San Diego Medical Center - Hillcrest; 🇺🇸 San Diego, California, United States

San Diego VA Medical Center; 🇺🇸 San Diego, California, United States

UCSF Medical Center-Mount Zion; 🇺🇸 San Francisco, California, United States

John Muir Medical Center-Walnut Creek; 🇺🇸 Walnut Creek, California, United States

UCHealth University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States

Rocky Mountain Gynecologic Oncology PC; 🇺🇸 Englewood, Colorado, United States

Hartford Hospital; 🇺🇸 Hartford, Connecticut, United States

Smilow Cancer Hospital Care Center at Saint Francis; 🇺🇸 Hartford, Connecticut, United States

The Hospital of Central Connecticut; 🇺🇸 New Britain, Connecticut, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

Beebe Medical Center; 🇺🇸 Lewes, Delaware, United States

Christiana Care Health System-Christiana Hospital; 🇺🇸 Newark, Delaware, United States

MedStar Washington Hospital Center; 🇺🇸 Washington, District of Columbia, United States

Morton Plant Hospital; 🇺🇸 Clearwater, Florida, United States

Mayo Clinic in Florida; 🇺🇸 Jacksonville, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center; 🇺🇸 Miami, Florida, United States

AdventHealth Orlando; 🇺🇸 Orlando, Florida, United States

Orlando Health Cancer Institute; 🇺🇸 Orlando, Florida, United States

Central Georgia Gynecologic Oncology; 🇺🇸 Macon, Georgia, United States

Memorial Health University Medical Center; 🇺🇸 Savannah, Georgia, United States

Pali Momi Medical Center; 🇺🇸 'Aiea, Hawaii, United States

Hawaii Cancer Care Inc - Waterfront Plaza; 🇺🇸 Honolulu, Hawaii, United States

Queen's Medical Center; 🇺🇸 Honolulu, Hawaii, United States

Straub Clinic and Hospital; 🇺🇸 Honolulu, Hawaii, United States

University of Hawaii Cancer Center; 🇺🇸 Honolulu, Hawaii, United States

Queen's Cancer Center - Kuakini; 🇺🇸 Honolulu, Hawaii, United States

The Cancer Center of Hawaii-Liliha; 🇺🇸 Honolulu, Hawaii, United States

Kapiolani Medical Center for Women and Children; 🇺🇸 Honolulu, Hawaii, United States

Wilcox Memorial Hospital and Kauai Medical Clinic; 🇺🇸 Lihue, Hawaii, United States

Maui Memorial Medical Center; 🇺🇸 Wailuku, Hawaii, United States

Pacific Cancer Institute of Maui; 🇺🇸 Wailuku, Hawaii, United States

Saint Alphonsus Cancer Care Center-Boise; 🇺🇸 Boise, Idaho, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center; 🇺🇸 Chicago, Illinois, United States

Advocate Sherman Hospital; 🇺🇸 Elgin, Illinois, United States

Hinsdale Hematology Oncology Associates Incorporated; 🇺🇸 Hinsdale, Illinois, United States

Sudarshan K Sharma MD Limited-Gynecologic Oncology; 🇺🇸 Hinsdale, Illinois, United States

Elkhart Clinic; 🇺🇸 Elkhart, Indiana, United States

Michiana Hematology Oncology PC-Elkhart; 🇺🇸 Elkhart, Indiana, United States

Elkhart General Hospital; 🇺🇸 Elkhart, Indiana, United States

Ascension Saint Vincent Indianapolis Hospital; 🇺🇸 Indianapolis, Indiana, United States

Community Howard Regional Health; 🇺🇸 Kokomo, Indiana, United States

IU Health La Porte Hospital; 🇺🇸 La Porte, Indiana, United States

Michiana Hematology Oncology PC-Mishawaka; 🇺🇸 Mishawaka, Indiana, United States

Saint Joseph Regional Medical Center-Mishawaka; 🇺🇸 Mishawaka, Indiana, United States

Michiana Hematology Oncology PC-Plymouth; 🇺🇸 Plymouth, Indiana, United States

Memorial Hospital of South Bend; 🇺🇸 South Bend, Indiana, United States

South Bend Clinic; 🇺🇸 South Bend, Indiana, United States

Northern Indiana Cancer Research Consortium; 🇺🇸 South Bend, Indiana, United States

Michiana Hematology Oncology PC-Westville; 🇺🇸 Westville, Indiana, United States

McFarland Clinic - Ames; 🇺🇸 Ames, Iowa, United States

Mercy Cancer Center-West Lakes; 🇺🇸 Clive, Iowa, United States

UI Health Care Mission Cancer and Blood - West Des Moines Clinic; 🇺🇸 Clive, Iowa, United States

Iowa Methodist Medical Center; 🇺🇸 Des Moines, Iowa, United States

Iowa-Wide Oncology Research Coalition NCORP; 🇺🇸 Des Moines, Iowa, United States

UI Health Care Mission Cancer and Blood - Des Moines Clinic; 🇺🇸 Des Moines, Iowa, United States

Mercy Medical Center - Des Moines; 🇺🇸 Des Moines, Iowa, United States

UI Health Care Mission Cancer and Blood - Laurel Clinic; 🇺🇸 Des Moines, Iowa, United States

University of Iowa/Holden Comprehensive Cancer Center; 🇺🇸 Iowa City, Iowa, United States

Methodist West Hospital; 🇺🇸 West Des Moines, Iowa, United States

Mercy Medical Center-West Lakes; 🇺🇸 West Des Moines, Iowa, United States

Cancer Center of Kansas - Chanute; 🇺🇸 Chanute, Kansas, United States

Cancer Center of Kansas - Dodge City; 🇺🇸 Dodge City, Kansas, United States

Cancer Center of Kansas - El Dorado; 🇺🇸 El Dorado, Kansas, United States

Cancer Center of Kansas - Fort Scott; 🇺🇸 Fort Scott, Kansas, United States

Cancer Center of Kansas-Independence; 🇺🇸 Independence, Kansas, United States

University of Kansas Cancer Center; 🇺🇸 Kansas City, Kansas, United States

Cancer Center of Kansas-Kingman; 🇺🇸 Kingman, Kansas, United States

Lawrence Memorial Hospital; 🇺🇸 Lawrence, Kansas, United States

Cancer Center of Kansas-Liberal; 🇺🇸 Liberal, Kansas, United States

Cancer Center of Kansas - McPherson; 🇺🇸 McPherson, Kansas, United States

Cancer Center of Kansas - Newton; 🇺🇸 Newton, Kansas, United States

Cancer Center of Kansas - Parsons; 🇺🇸 Parsons, Kansas, United States

Cancer Center of Kansas - Pratt; 🇺🇸 Pratt, Kansas, United States

Cancer Center of Kansas - Salina; 🇺🇸 Salina, Kansas, United States

Cancer Center of Kansas - Wellington; 🇺🇸 Wellington, Kansas, United States

Associates In Womens Health; 🇺🇸 Wichita, Kansas, United States

Cancer Center of Kansas-Wichita Medical Arts Tower; 🇺🇸 Wichita, Kansas, United States

Ascension Via Christi Hospitals Wichita; 🇺🇸 Wichita, Kansas, United States

Cancer Center of Kansas - Wichita; 🇺🇸 Wichita, Kansas, United States

Wichita NCI Community Oncology Research Program; 🇺🇸 Wichita, Kansas, United States

Cancer Center of Kansas - Winfield; 🇺🇸 Winfield, Kansas, United States

Baptist Health Lexington; 🇺🇸 Lexington, Kentucky, United States

University of Kentucky/Markey Cancer Center; 🇺🇸 Lexington, Kentucky, United States

The James Graham Brown Cancer Center at University of Louisville; 🇺🇸 Louisville, Kentucky, United States

MaineHealth Maine Medical Center - Portland; 🇺🇸 Portland, 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

Christiana Care - Union Hospital; 🇺🇸 Elkton, Maryland, United States

Baystate Medical Center; 🇺🇸 Springfield, Massachusetts, United States

UMass Memorial Medical Center - Memorial Division; 🇺🇸 Worcester, Massachusetts, United States

Michigan Cancer Research Consortium NCORP; 🇺🇸 Ann Arbor, Michigan, United States

Trinity Health Saint Joseph Mercy Hospital Ann Arbor; 🇺🇸 Ann Arbor, Michigan, United States

Corewell Health Dearborn Hospital; 🇺🇸 Dearborn, Michigan, United States

Henry Ford Health Saint John Hospital; 🇺🇸 Detroit, Michigan, United States

Hurley Medical Center; 🇺🇸 Flint, Michigan, United States

Genesys Regional Medical Center-West Flint Campus; 🇺🇸 Flint, Michigan, United States

Allegiance Health; 🇺🇸 Jackson, Michigan, United States

Bronson Methodist Hospital; 🇺🇸 Kalamazoo, Michigan, United States

West Michigan Cancer Center; 🇺🇸 Kalamazoo, Michigan, United States

Ascension Borgess Hospital; 🇺🇸 Kalamazoo, Michigan, United States

University of Michigan Health - Sparrow Lansing; 🇺🇸 Lansing, Michigan, United States

Trinity Health Saint Mary Mercy Livonia Hospital; 🇺🇸 Livonia, Michigan, United States

Corewell Health Lakeland Hospitals - Niles Hospital; 🇺🇸 Niles, Michigan, United States

Trinity Health Saint Joseph Mercy Oakland Hospital; 🇺🇸 Pontiac, Michigan, United States

Lake Huron Medical Center; 🇺🇸 Port Huron, Michigan, United States

Corewell Health William Beaumont University Hospital; 🇺🇸 Royal Oak, Michigan, United States

MyMichigan Medical Center Saginaw; 🇺🇸 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

Henry Ford Health Warren Hospital; 🇺🇸 Warren, Michigan, United States

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States

Saint Dominic-Jackson Memorial Hospital; 🇺🇸 Jackson, Mississippi, United States

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

Singing River Hospital; 🇺🇸 Pascagoula, Mississippi, United States

MU Health - University Hospital/Ellis Fischel Cancer Center; 🇺🇸 Columbia, Missouri, United States

Phelps Health Delbert Day Cancer Institute; 🇺🇸 Rolla, Missouri, United States

SSM Health Saint Louis University Hospital; 🇺🇸 Saint Louis, Missouri, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Cancer Research for the Ozarks NCORP; 🇺🇸 Springfield, Missouri, United States

Mercy Hospital Springfield; 🇺🇸 Springfield, Missouri, United States

CoxHealth South Hospital; 🇺🇸 Springfield, Missouri, United States

Nebraska Methodist Hospital; 🇺🇸 Omaha, Nebraska, United States

Women's Cancer Center of Nevada; 🇺🇸 Las Vegas, Nevada, United States

Center of Hope at Renown Medical Center; 🇺🇸 Reno, Nevada, United States

Renown Regional Medical Center; 🇺🇸 Reno, Nevada, United States

Cooper Hospital University Medical Center; 🇺🇸 Camden, New Jersey, United States

Morristown Medical Center; 🇺🇸 Morristown, New Jersey, United States

Virtua Memorial; 🇺🇸 Mount Holly, New Jersey, United States

Rutgers New Jersey Medical School; 🇺🇸 Newark, New Jersey, United States

Saint Luke's Hospital-Warren Campus; 🇺🇸 Phillipsburg, New Jersey, United States

Overlook Hospital; 🇺🇸 Summit, New Jersey, United States

Virtua Voorhees; 🇺🇸 Voorhees, New Jersey, United States

Southwest Gynecologic Oncology Associates Inc; 🇺🇸 Albuquerque, New Mexico, United States

University of New Mexico Cancer Center; 🇺🇸 Albuquerque, New Mexico, United States

Women's Cancer Care Associates LLC; 🇺🇸 Albany, New York, United States

Island Gynecologic Oncology; 🇺🇸 Brightwaters, New York, United States

State University of New York Downstate Medical Center; 🇺🇸 Brooklyn, New York, United States

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

New York Hospital Medical Center of Queens; 🇺🇸 Fresh Meadows, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Stony Brook University Medical Center; 🇺🇸 Stony Brook, New York, United States

Hope Women's Cancer Centers-Asheville; 🇺🇸 Asheville, North Carolina, United States

Cone Health Cancer Center at Alamance Regional; 🇺🇸 Burlington, North Carolina, United States

Carolinas Medical Center/Levine Cancer Institute; 🇺🇸 Charlotte, North Carolina, United States

Novant Health Presbyterian Medical Center; 🇺🇸 Charlotte, North Carolina, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States

Summa Health System - Akron Campus; 🇺🇸 Akron, Ohio, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Oklahoma Cancer Specialists and Research Institute-Tulsa; 🇺🇸 Tulsa, Oklahoma, United States

Jefferson Abington Hospital; 🇺🇸 Abington, Pennsylvania, United States

Lehigh Valley Hospital-Cedar Crest; 🇺🇸 Allentown, Pennsylvania, United States

Geisinger Medical Center; 🇺🇸 Danville, Pennsylvania, United States

Geisinger Medical Center-Cancer Center Hazleton; 🇺🇸 Hazleton, Pennsylvania, United States

Penn State Milton S Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

Pennsylvania Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Geisinger Medical Group; 🇺🇸 State College, Pennsylvania, United States

Reading Hospital; 🇺🇸 West Reading, Pennsylvania, United States

Geisinger Wyoming Valley/Henry Cancer Center; 🇺🇸 Wilkes-Barre, Pennsylvania, United States

Women and Infants Hospital; 🇺🇸 Providence, Rhode Island, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

South Carolina Oncology Associates PA; 🇺🇸 Columbia, South Carolina, 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

Vanderbilt University/Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

Parkland Memorial Hospital; 🇺🇸 Dallas, Texas, United States

Clements University Hospital; 🇺🇸 Dallas, Texas, United States

UT Southwestern/Simmons Cancer Center-Dallas; 🇺🇸 Dallas, Texas, United States

University of Texas Medical Branch; 🇺🇸 Galveston, Texas, United States

Lyndon Baines Johnson General Hospital; 🇺🇸 Houston, Texas, United States

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Scott and White Memorial Hospital; 🇺🇸 Temple, Texas, United States

University of Vermont Medical Center; 🇺🇸 Burlington, Vermont, United States

University of Virginia Cancer Center; 🇺🇸 Charlottesville, Virginia, United States

Virginia Oncology Associates-Hampton; 🇺🇸 Hampton, Virginia, United States

Virginia Oncology Associates - Norfolk; 🇺🇸 Norfolk, Virginia, United States

Virginia Commonwealth University/Massey Cancer Center; 🇺🇸 Richmond, Virginia, United States

Carilion Roanoke Memorial Hospital; 🇺🇸 Roanoke, Virginia, United States

PeaceHealth Medical Group PC; 🇺🇸 Bellingham, Washington, United States

Providence Regional Cancer Partnership; 🇺🇸 Everett, Washington, United States

Skagit Regional Health Cancer Care Center; 🇺🇸 Mount Vernon, Washington, United States

Harrison HealthPartners Hematology and Oncology-Poulsbo; 🇺🇸 Poulsbo, Washington, United States

Pacific Gynecology Specialists; 🇺🇸 Seattle, Washington, United States

Fred Hutchinson Cancer Center; 🇺🇸 Seattle, Washington, United States

Kaiser Permanente Washington; 🇺🇸 Seattle, Washington, United States

Swedish Medical Center-First Hill; 🇺🇸 Seattle, Washington, United States

University of Washington Medical Center - Northwest; 🇺🇸 Seattle, Washington, United States

University of Washington Medical Center - Montlake; 🇺🇸 Seattle, Washington, United States

Olympic Medical Cancer Care Center; 🇺🇸 Sequim, Washington, United States

Saint Michael Cancer Center; 🇺🇸 Silverdale, Washington, United States

Cancer Care Northwest - Spokane South; 🇺🇸 Spokane, Washington, United States

MultiCare Deaconess Cancer and Blood Specialty Center - Downtown; 🇺🇸 Spokane, Washington, United States

MultiCare Tacoma General Hospital; 🇺🇸 Tacoma, Washington, United States

Saint Joseph Medical Center; 🇺🇸 Tacoma, Washington, United States

Providence Saint Mary Regional Cancer Center; 🇺🇸 Walla Walla, Washington, United States

Wenatchee Valley Hospital and Clinics; 🇺🇸 Wenatchee, Washington, United States

Gundersen Lutheran Medical Center; 🇺🇸 La Crosse, Wisconsin, United States

University of Wisconsin Carbone Cancer Center - University Hospital; 🇺🇸 Madison, Wisconsin, United States

Aurora Saint Luke's Medical Center; 🇺🇸 Milwaukee, Wisconsin, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Aurora Sinai Medical Center; 🇺🇸 Milwaukee, Wisconsin, United States

Vince Lombardi Cancer Clinic - Oshkosh; 🇺🇸 Oshkosh, Wisconsin, United States

Vince Lombardi Cancer Clinic-Sheboygan; 🇺🇸 Sheboygan, Wisconsin, United States

Aurora West Allis Medical Center; 🇺🇸 West Allis, Wisconsin, United States