MedPath

Comparison of Standard of Care Treatment With a Triplet Combination of Targeted Immunotherapeutic Agents

Phase 2
Active, not recruiting
Conditions
Fallopian Tube Mucinous Adenocarcinoma
Ovarian Seromucinous Carcinoma
Platinum-Refractory Fallopian Tube Carcinoma
Platinum-Refractory Ovarian Carcinoma
Platinum-Refractory Primary Peritoneal Carcinoma
Recurrent Fallopian Tube Clear Cell Adenocarcinoma
Recurrent Fallopian Tube Endometrioid Adenocarcinoma
Recurrent Fallopian Tube High Grade Serous Adenocarcinoma
Recurrent Fallopian Tube Mucinous Adenocarcinoma
Recurrent Fallopian Tube Transitional Cell Carcinoma
Interventions
Procedure: Biospecimen Collection
Procedure: Computed Tomography
Procedure: Computed Tomography with Contrast
Procedure: Echocardiography Test
Procedure: Magnetic Resonance Imaging
Procedure: Multigated Acquisition Scan
Registration Number
NCT04739800
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

This phase II trial studies the possible benefits of treatment with different combinations of the drugs durvalumab, olaparib and cediranib vs. the usual treatment in patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of improvement with platinum therapy (recurrent platinum resistant). Usual treatment is the type of treatment most patients with this condition receive if they are not part of a clinical study. Combination therapies studied in this trial include MEDI4736 (durvalumab) plus olaparib and cediranib, durvalumab and cediranib, or olaparib and cediranib. Monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumors cells to grow and spread. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Cediranib may stop the growth of tumor cells by blocking VEGF (an enzyme). needed for cell growth. Giving different combinations of durvalumab, olaparib and cediranib may work better in increasing the duration of time that the cancer does not progress compared to the usual treatment.

Detailed Description

PRIMARY OBJECTIVE:

I. To assess the efficacy of the combinations durvalumab (MEDI4736) plus olaparib and cediranib, durvalumab (MEDI4736) plus cediranib, or olaparib and cediranib, as measured by progression-free survival (PFS), as compared to physician's choice standard of care chemotherapy, in patients with recurrent platinum-resistant ovarian, primary peritoneal or fallopian tube cancer who had prior bevacizumab.

SECONDARY OBJECTIVES:

I. To assess the efficacy of the combinations durvalumab (MEDI4736) plus olaparib and cediranib, durvalumab (MEDI4736) plus cediranib, or olaparib and cediranib, as measured by overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as compared to physician's choice standard of care chemotherapy, in patients with recurrent platinum-resistant ovarian, primary peritoneal or fallopian tube cancer who had prior bevacizumab.

II. To assess the efficacy of the combinations durvalumab (MEDI4736) plus olaparib and cediranib, durvalumab (MEDI4736) plus cediranib, or olaparib and cediranib, as measured by overall survival (OS), as compared to physician's choice standard of care chemotherapy, in patients with recurrent platinum-resistant ovarian, primary peritoneal or fallopian tube cancer who had prior bevacizumab.

OUTLINE: Patients are randomized to 1 of 4 arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening and as clinically indicated on study. Patients also undergo collection of blood and computed tomography (CT) with contrast during screening, and CT or magnetic resonance imaging (MRI) scans throughout the trial.

ARM II: Patients receive durvalumab IV over 60 minutes on day 1, cediranib maleate orally (PO) once daily (QD) Monday through Friday, and olaparib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.

ARM III: Patients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.

ARM IV: Patients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.

After completion of study treatment, patients are followed up periodically for up to 5 years.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Female
Target Recruitment
120
Inclusion Criteria
  • Women with recurrent/persistent platinum-resistant ovarian, primary peritoneal, or fallopian tube cancers; platinum-resistant disease is defined as progression within < 6 months from completion of platinum based therapy. The date should be calculated from the last administered dose of platinum therapy

  • Patients must have histologically or cytologically confirmed ovarian cancer, peritoneal cancer or fallopian tube cancer and must have a histological diagnosis of high grade serous, grade 3 endometrioid or clear cell carcinoma based on local histopathological findings. Patients with low grade serous, grade 1 or 2 endometrioid, mixed epithelial, undifferentiated carcinoma, or mucinous carcinoma histologies are also eligible, provided that the patient has a known deleterious BRCA1 or BRCA2 mutation identified through testing at a clinical laboratory. Histologic confirmation of the original primary tumor is required via the pathology report (upload of report required). Confirmation of BRCA1 and BRCA2 germline and/or somatic mutation status and hormone receptor (HR) status is required for all entered patients (if available) via testing report (upload of report[s] required)

  • Evaluable disease - defined as RECIST 1.1 measurable disease OR non-measurable disease (defined as solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions OR ascites and/or pleural effusion that has been pathologically demonstrated to be disease-related in the setting of a CA125 >= 2 x upper limit of normal [ULN])

  • Prior therapy:

    • At least two prior treatment regimens (including primary therapy) but up to 5 lines of systemic anticancer therapy. Hormonal therapy (such as tamoxifen, aromatase inhibitors) will not count as a previous treatment regimen.
    • Prior use of bevacizumab in the upfront or recurrent setting is required.
    • Prior use of PARP inhibitor is allowed.
    • Prior use of immune checkpoint blockade (e.g., a PD-L1/PD-1inhibitor or a CTLA-4 inhibitor) is allowed
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

  • Absolute neutrophil count (ANC) >= 1,500/mcL

  • Hemoglobin > 10 g/dL

  • Platelets >= 100,000/mcL

  • Creatinine clearance (CrCL) or estimated glomerular filtration rate (eGFR) of > 50 mL/min estimated 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)

  • Urine protein: creatinine ratio (UPC) of =< 1

  • Total serum bilirubin level =< 1.5 x ULN (patients with known Gilbert's disease who have bilirubin level =< 3 x ULN may be enrolled)

  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN

  • Age >= 18 years

  • Body weight > 30 kg

  • Adequately controlled blood pressure (systolic blood pressure [SBP] =< 140; diastolic blood pressure [DBP] =< 90 mmHg) on a maximum of three antihypertensive medications. Patients must have a BP of =< 140/90 mmHg taken in the clinic setting by a medical professional within 2 weeks prior to study registration. It is strongly recommended that patients who are on three antihypertensive medications be followed by a cardiologist or a primary care physician for management of BP while on protocol. Patients must be willing and able to check and record daily blood pressure readings. BP cuffs will be provided to patients randomized to the cediranib-containing arms

  • Adequately controlled thyroid dysfunction with no symptoms of thyroid dysfunction and normal thyroid stimulating hormone (TSH). If TSH is not within normal range despite no symptoms of thyroid dysfunction, normal free T4 level is required

  • Able to swallow and retain oral medications and no gastrointestinal (GI) illnesses that would preclude absorption of olaparib and cediranib as judged by treating physician

  • Toxicities of prior therapy (excepting alopecia and vitiligo), should be resolved to less than or equal to grade 1 as per Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  • Women of childbearing potential (WOCBP) must agree to use two forms of birth control (hormonal or barrier method of birth control; abstinence). Note: Definition of women of no longer having childbearing potential: Postmenopausal or evidence of non-childbearing status for women of childbearing potential as confirmed by a negative urine or serum pregnancy test within 7 days prior to start of study treatment. Postmenopausal is defined as: Age >= 60 years, or age < 60 with any one or more of the conditions below:

    • Amenorrhoeic for >= 1 year in the absence of chemotherapy and/or hormonal treatments,
    • Luteinizing hormone and/or follicle stimulating hormone and/or estradiol levels in the post-menopausal range,
    • Radiation-induced oophorectomy with last menses > 1 year ago,
    • Chemotherapy-induced menopause with > 1 year interval since last menses,
    • Surgical sterilization (bilateral oophorectomy or hysterectomy)
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and authorization permitting release of personal health information

Exclusion Criteria
  • Primary platinum-refractory disease defined as progression during first-line platinum-based chemotherapy

  • Rising CA-125 only without RECIST 1.1 evaluable disease

  • Prior therapy:

    • Patients who have had chemotherapy, investigational drugs or radiotherapy within 3 weeks prior to study registration or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier.

    • Patients may not have had hormonal therapy within 2 weeks of study registration. Patients receiving raloxifene for bone health as per Food and Drug Administration (FDA) indication may remain on raloxifene absent other drug interactions.

    • Prior use of concurrent olaparib and cediranib combination.

    • Patients who have experienced immune-mediated adverse events requiring dose modification or discontinuation.

    • For patients who have received prior PARP inhibitor:

      • Patients who have required dose modification or dose reduction of olaparib will not be eligible, as they will not be able to start this study at full dose.
      • Patients who have required dose reduction of non-olaparib PARP inhibitors for hematologic adverse events will not be eligible (Note: niraparib that is initiated at 200mg daily per weight and platelet guidelines is not considered a dose reduction).
      • Patients who required dose-reduction of non-olaparib PARP inhibitors for non-hematologic adverse events may be eligible after discussion with the Study Chair if the treating investigator feels that they could appropriately receive olaparib at full dose.
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 3 months prior to study registration

  • Current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowel obstruction within 3 months of study registration except temporary (< 24 hr) improved with medical management, within last 3 months

  • Any prior grade >= 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE > grade 1

  • Dependency on IV hydration or total parenteral nutrition (TPN)

  • Pregnant women. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with these drugs, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study

  • 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

  • Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans should not be included on this study, since neurologic dysfunction may confound the evaluation of neurologic and other adverse events. Patients with treated brain metastases and resolution of any associated symptoms must demonstrate stable post-therapeutic imaging for at least 6 months following therapy prior to starting study registration

  • Patients who have the following clinical conditions are considered to be at increased risk for cardiac toxicities. Patients with any cardiac history of the following conditions:

    • History of myocardial infarction or myocarditis within six months of study registration
    • Unstable angina
    • Resting electrocardiogram (ECG) with clinically significant abnormal findings.
    • New York Heart Association functional classification of III or IV
  • If cardiac function assessment is clinically indicated or performed: left ventricular ejection fraction (LVEF) less than normal per institutional guidelines, or < 55%, if threshold for normal not otherwise specified by institutional guidelines. Patients with the following risk factors should have a baseline cardiac function assessment:

    • Prior treatment with anthracyclines
    • Prior treatment with trastuzumab or T-DM1
    • Prior central thoracic radiation therapy (RT), including RT to the heart
    • History of myocardial infarction within 6 to 12 months (Patients with history of myocardial infarction within 6 months are excluded from the study)
    • Prior history of impaired cardiac function
  • History of stroke or transient ischemic attack within six months of study registration

  • Clinically significant peripheral vascular disease or vascular disease (aortic aneurysm or aortic dissection)

  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study treatment. Patients must have recovered from any effects of any major surgery and surgical wound should have healed prior to starting treatment. Note: Local surgery of isolated lesions for palliative intent is acceptable

  • Evidence of coagulopathy or bleeding diathesis. Therapeutic anticoagulation for prior thromboembolic events, including warfarin, is permitted. Patients receiving warfarin are recommended to have careful monitoring of international normalized ratio (INR)

  • Evidence suggestive of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated. No prior allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUBCT)

  • Human immunodeficiency virus (HIV) positive patients due to potential drug and drug interactions

  • Patients may not use any complementary or alternative medicines including natural herbal products or folk remedies as they may interfere with the effectiveness of the study treatments

  • Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment. Note: Patients, if enrolled, should not receive live vaccine whilst receiving study treatment and up to 30 days after the last dose of study treatment

  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (other than atrial fibrillation with controlled ventricular rate), or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring adverse events or compromise the ability of the patient to given written informed consent

  • Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4. Dihydropyridine calcium-channel blockers are permitted for management of hypertension

  • Current or prior use of immunosuppressive medication within 14 days of study registration. The following are exceptions to this criterion:

    • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
    • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
    • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab, olaparib, or cediranib

  • Patients with active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment

  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B (known positive hepatitis B virus [HBV] surface antigen (HBsAg) result), or hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for hepatitis C virus (HCV) ribonucleic acid (RNA)

  • Patients who have a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm III (durvalumab, cediranib maleate)Multigated Acquisition ScanPatients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm IV (cediranib maleate, olaparib)Biospecimen CollectionPatients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm IV (cediranib maleate, olaparib)Cediranib MaleatePatients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm IV (cediranib maleate, olaparib)Computed TomographyPatients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm IV (cediranib maleate, olaparib)Computed Tomography with ContrastPatients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm IV (cediranib maleate, olaparib)Echocardiography TestPatients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm IV (cediranib maleate, olaparib)Magnetic Resonance ImagingPatients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm IV (cediranib maleate, olaparib)OlaparibPatients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))Computed TomographyPatients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))Computed Tomography with ContrastPatients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))Biospecimen CollectionPatients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))Echocardiography TestPatients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))Magnetic Resonance ImagingPatients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))Multigated Acquisition ScanPatients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))PaclitaxelPatients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))Pegylated Liposomal Doxorubicin HydrochloridePatients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))Topotecan HydrochloridePatients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm II (durvalumab, cediranib maleate, olaparib)Biospecimen CollectionPatients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm II (durvalumab, cediranib maleate, olaparib)Cediranib MaleatePatients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm II (durvalumab, cediranib maleate, olaparib)Computed TomographyPatients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm II (durvalumab, cediranib maleate, olaparib)Computed Tomography with ContrastPatients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm II (durvalumab, cediranib maleate, olaparib)DurvalumabPatients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm II (durvalumab, cediranib maleate, olaparib)Echocardiography TestPatients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm II (durvalumab, cediranib maleate, olaparib)Magnetic Resonance ImagingPatients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm II (durvalumab, cediranib maleate, olaparib)Multigated Acquisition ScanPatients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm II (durvalumab, cediranib maleate, olaparib)OlaparibPatients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm III (durvalumab, cediranib maleate)Biospecimen CollectionPatients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm III (durvalumab, cediranib maleate)Cediranib MaleatePatients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm III (durvalumab, cediranib maleate)Computed TomographyPatients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm III (durvalumab, cediranib maleate)Computed Tomography with ContrastPatients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm III (durvalumab, cediranib maleate)DurvalumabPatients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm III (durvalumab, cediranib maleate)Echocardiography TestPatients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Arm III (durvalumab, cediranib maleate)Magnetic Resonance ImagingPatients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.
Primary Outcome Measures
NameTimeMethod
Progression Free SurvivalFrom start of treatment to time of progression or death, whichever occurs first. Median follow-up time was 4.8 months (Inter-Quartile Range: 2.0-7.9 months).

The relationship of randomized treatment assignment to progression free survival. The RECIST 1.1 criteria are used for disease progression. Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Secondary Outcome Measures
NameTimeMethod
Duration of ResponseThroughout study treatment, up to 10.6 months.

Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. Duration of response was defined as the time from the first documentation of objective tumor response (complete response (CR) or partial response (PR)) to the first documented progressive disease (PD), or to death due to any cause, whichever occurs first.

Per RECIST, Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as an \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Reporting the number of months from complete or partial response until disease progression, death or censoring, whichever occurs first. In the absence of disease progression or death, censoring time is based on date of last CT scan.

Overall SurvivalTime from study entry to date of death from any cause, or termination by the DMC. The median followup time was 4.3 months. The maximum followup time was 11 months. Patients are no longer being assessed.

Overall survival will be presented by Kaplan Meier methods. Overall Survival (OS) is defined as the duration of time from study entry to date of death from any cause. A subject who has not died will be censored on the date that they were last known to be alive.

Count of Participants With a Grade 3 (or Higher) Adverse EventFrom the start of treatment until disease progression/recurrence or termination by the DMC. The median followup time was 4.3 months. The maximum followup time was 11 months. Patients are no longer being assessed.

The number of patients (in each reporting group) who experienced a grade 3 (or higher) adverse event

Objective Response RateFrom the start of the treatment until disease progression/recurrence, or termination by the DMC. The median followup time was 4.3 months. The maximum followup time was 11 months. Patients are no longer being assessed.

Determination of response should take into consideration all target and non-target lesions. Here are the definitions of CR, PR, PD and SD: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters (i.e. the nadir) while on study. The CI is the Jeffreys interval.

Trial Locations

Locations (391)

CoxHealth South Hospital

🇺🇸

Springfield, Missouri, United States

Missouri Baptist Sullivan Hospital

🇺🇸

Sullivan, Missouri, United States

TriHealth Cancer Institute-Westside

🇺🇸

Cincinnati, Ohio, United States

TriHealth Cancer Institute-Anderson

🇺🇸

Cincinnati, Ohio, United States

Case Western Reserve University

🇺🇸

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

Mount Carmel East Hospital

🇺🇸

Columbus, Ohio, United States

San Juan Community Oncology Group

🇵🇷

San Juan, Puerto Rico

Centro Comprensivo de Cancer de UPR

🇵🇷

San Juan, Puerto Rico

San Juan City Hospital

🇵🇷

San Juan, Puerto Rico

Providence Alaska Medical Center

🇺🇸

Anchorage, Alaska, United States

Fairbanks Memorial Hospital

🇺🇸

Fairbanks, Alaska, United States

CTCA at Western Regional Medical Center

🇺🇸

Goodyear, Arizona, United States

Cancer Center at Saint Joseph's

🇺🇸

Phoenix, Arizona, United States

Mercy Hospital Fort Smith

🇺🇸

Fort Smith, Arkansas, United States

CHI Saint Vincent Cancer Center Hot Springs

🇺🇸

Hot Springs, Arkansas, United States

University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

Mission Hope Medical Oncology - Arroyo Grande

🇺🇸

Arroyo Grande, California, United States

Sutter Auburn Faith Hospital

🇺🇸

Auburn, California, United States

Sutter Cancer Centers Radiation Oncology Services-Auburn

🇺🇸

Auburn, California, United States

Alta Bates Summit Medical Center-Herrick Campus

🇺🇸

Berkeley, California, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center

🇺🇸

Burbank, California, United States

Sutter Cancer Centers Radiation Oncology Services-Cameron Park

🇺🇸

Cameron Park, California, United States

Eden Hospital Medical Center

🇺🇸

Castro Valley, California, United States

John Muir Medical Center-Concord

🇺🇸

Concord, California, United States

Sutter Davis Hospital

🇺🇸

Davis, California, United States

City of Hope Comprehensive Cancer Center

🇺🇸

Duarte, California, United States

Palo Alto Medical Foundation-Fremont

🇺🇸

Fremont, California, United States

City of Hope Antelope Valley

🇺🇸

Lancaster, California, United States

Los Angeles General Medical Center

🇺🇸

Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center

🇺🇸

Los Angeles, California, United States

Memorial Medical Center

🇺🇸

Modesto, California, United States

Palo Alto Medical Foundation-Camino Division

🇺🇸

Mountain View, California, United States

Palo Alto Medical Foundation-Gynecologic Oncology

🇺🇸

Mountain View, California, United States

Sacred Heart Hospital

🇺🇸

Pensacola, Florida, United States

Northside Hospital

🇺🇸

Atlanta, Georgia, United States

Illinois CancerCare-Dixon

🇺🇸

Dixon, Illinois, United States

Illinois CancerCare-Macomb

🇺🇸

Macomb, Illinois, United States

Greater Regional Medical Center

🇺🇸

Creston, Iowa, United States

Mercy Medical Center - Des Moines

🇺🇸

Des Moines, Iowa, United States

Fairview Ridges Hospital

🇺🇸

Burnsville, Minnesota, United States

Columbus Oncology and Hematology Associates Inc

🇺🇸

Columbus, Ohio, United States

Riverside Methodist Hospital

🇺🇸

Columbus, Ohio, United States

Grant Medical Center

🇺🇸

Columbus, Ohio, United States

The Mark H Zangmeister Center

🇺🇸

Columbus, Ohio, United States

Mount Carmel Health Center West

🇺🇸

Columbus, Ohio, United States

Doctors Hospital

🇺🇸

Columbus, Ohio, United States

Miami Valley Hospital

🇺🇸

Dayton, Ohio, United States

Saint Rita's Medical Center

🇺🇸

Lima, Ohio, United States

Billings Clinic-Cody

🇺🇸

Cody, Wyoming, United States

Welch Cancer Center

🇺🇸

Sheridan, Wyoming, United States

Alaska Women's Cancer Care

🇺🇸

Anchorage, Alaska, United States

Sutter Roseville Medical Center

🇺🇸

Roseville, California, United States

Sutter Medical Center Sacramento

🇺🇸

Sacramento, California, United States

Anchorage Oncology Centre

🇺🇸

Anchorage, Alaska, United States

Cancer Center-Metro Medical Center Bayamon

🇵🇷

Bayamon, Puerto Rico

Saint Mary Corwin Medical Center

🇺🇸

Pueblo, Colorado, United States

Katmai Oncology Group

🇺🇸

Anchorage, Alaska, United States

Illinois CancerCare-Eureka

🇺🇸

Eureka, Illinois, United States

Anchorage Associates in Radiation Medicine

🇺🇸

Anchorage, Alaska, United States

Anchorage Radiation Therapy Center

🇺🇸

Anchorage, Alaska, United States

Alaska Breast Care and Surgery LLC

🇺🇸

Anchorage, Alaska, United States

Alaska Oncology and Hematology LLC

🇺🇸

Anchorage, Alaska, United States

Sutter Cancer Centers Radiation Oncology Services-Roseville

🇺🇸

Roseville, California, United States

Longmont United Hospital

🇺🇸

Longmont, Colorado, United States

Palo Alto Medical Foundation Health Care

🇺🇸

Palo Alto, California, United States

California Pacific Medical Center-Pacific Campus

🇺🇸

San Francisco, California, United States

Pacific Central Coast Health Center-San Luis Obispo

🇺🇸

San Luis Obispo, California, United States

Palo Alto Medical Foundation-Santa Cruz

🇺🇸

Santa Cruz, California, United States

Mission Hope Medical Oncology - Santa Maria

🇺🇸

Santa Maria, California, United States

Sutter Pacific Medical Foundation

🇺🇸

Santa Rosa, California, United States

City of Hope South Pasadena

🇺🇸

South Pasadena, California, United States

Palo Alto Medical Foundation-Sunnyvale

🇺🇸

Sunnyvale, California, United States

City of Hope Upland

🇺🇸

Upland, California, United States

Sutter Solano Medical Center/Cancer Center

🇺🇸

Vallejo, California, United States

John Muir Medical Center-Walnut Creek

🇺🇸

Walnut Creek, California, United States

Rocky Mountain Cancer Centers-Aurora

🇺🇸

Aurora, Colorado, United States

Rocky Mountain Cancer Centers-Boulder

🇺🇸

Boulder, Colorado, United States

Rocky Mountain Cancer Centers - Centennial

🇺🇸

Centennial, Colorado, United States

Penrose-Saint Francis Healthcare

🇺🇸

Colorado Springs, Colorado, United States

Rocky Mountain Cancer Centers-Penrose

🇺🇸

Colorado Springs, Colorado, United States

AdventHealth Porter

🇺🇸

Denver, Colorado, United States

Mercy Medical Center

🇺🇸

Durango, Colorado, United States

Southwest Oncology PC

🇺🇸

Durango, Colorado, United States

Saint Anthony Hospital

🇺🇸

Lakewood, Colorado, United States

Rocky Mountain Cancer Centers-Littleton

🇺🇸

Littleton, Colorado, United States

AdventHealth Littleton

🇺🇸

Littleton, Colorado, United States

Rocky Mountain Cancer Centers-Sky Ridge

🇺🇸

Lone Tree, Colorado, United States

Rocky Mountain Cancer Centers-Longmont

🇺🇸

Longmont, Colorado, United States

Banner McKee Medical Center

🇺🇸

Loveland, Colorado, United States

AdventHealth Parker

🇺🇸

Parker, Colorado, United States

The Carle Foundation Hospital

🇺🇸

Urbana, Illinois, United States

Danbury Hospital

🇺🇸

Danbury, Connecticut, United States

Norwalk Hospital

🇺🇸

Norwalk, Connecticut, United States

CTCA at Southeastern Regional Medical Center

🇺🇸

Newnan, 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

Walter Knox Memorial Hospital

🇺🇸

Emmett, Idaho, United States

Saint Luke's Cancer Institute - Fruitland

🇺🇸

Fruitland, Idaho, United States

Idaho Urologic Institute-Meridian

🇺🇸

Meridian, 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

OSF Saint Anthony's Health Center

🇺🇸

Alton, Illinois, United States

Rush - Copley Medical Center

🇺🇸

Aurora, Illinois, United States

Illinois CancerCare-Bloomington

🇺🇸

Bloomington, Illinois, United States

Illinois CancerCare-Canton

🇺🇸

Canton, Illinois, United States

Memorial Hospital of Carbondale

🇺🇸

Carbondale, Illinois, United States

SIH Cancer Institute

🇺🇸

Carterville, Illinois, United States

Illinois CancerCare-Carthage

🇺🇸

Carthage, Illinois, United States

Centralia Oncology Clinic

🇺🇸

Centralia, 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

Carle Physician Group-Effingham

🇺🇸

Effingham, Illinois, United States

Crossroads Cancer Center

🇺🇸

Effingham, Illinois, United States

NorthShore University HealthSystem-Evanston Hospital

🇺🇸

Evanston, Illinois, United States

Illinois CancerCare-Galesburg

🇺🇸

Galesburg, Illinois, United States

Western Illinois Cancer Treatment Center

🇺🇸

Galesburg, Illinois, United States

Northwestern Medicine Cancer Center Delnor

🇺🇸

Geneva, Illinois, United States

NorthShore University HealthSystem-Glenbrook Hospital

🇺🇸

Glenview, Illinois, United States

Ingalls Memorial Hospital

🇺🇸

Harvey, 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

Illinois CancerCare-Kewanee Clinic

🇺🇸

Kewanee, Illinois, United States

Carle Physician Group-Mattoon/Charleston

🇺🇸

Mattoon, Illinois, United States

SSM Health Good Samaritan

🇺🇸

Mount Vernon, 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

University of Chicago Medicine-Orland Park

🇺🇸

Orland Park, Illinois, United States

Illinois CancerCare-Ottawa Clinic

🇺🇸

Ottawa, Illinois, United States

Illinois CancerCare-Pekin

🇺🇸

Pekin, Illinois, United States

Illinois CancerCare-Peoria

🇺🇸

Peoria, Illinois, United States

Methodist Medical Center of Illinois

🇺🇸

Peoria, Illinois, United States

Illinois CancerCare-Peru

🇺🇸

Peru, Illinois, United States

Valley Radiation Oncology

🇺🇸

Peru, Illinois, United States

Illinois CancerCare-Princeton

🇺🇸

Princeton, 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

HIMA San Pablo Oncologic Hospital

🇵🇷

Caguas, Puerto Rico

Northwestern Medicine Cancer Center Warrenville

🇺🇸

Warrenville, Illinois, United States

Illinois CancerCare - Washington

🇺🇸

Washington, Illinois, United States

Rush-Copley Healthcare Center

🇺🇸

Yorkville, Illinois, United States

Midwestern Regional Medical Center

🇺🇸

Zion, Illinois, United States

Memorial Hospital of South Bend

🇺🇸

South Bend, 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

Mercy Hospital

🇺🇸

Coon Rapids, Minnesota, United States

Oncology Associates at Mercy Medical Center

🇺🇸

Cedar Rapids, 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

Alegent Health Mercy Hospital

🇺🇸

Council Bluffs, Iowa, United States

UI Health Care Mission Cancer and Blood - Laurel Clinic

🇺🇸

Des Moines, 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

Mercy Medical Center-West Lakes

🇺🇸

West Des Moines, Iowa, United States

Central Care Cancer Center - Garden City

🇺🇸

Garden City, Kansas, United States

Central Care Cancer Center - Great Bend

🇺🇸

Great Bend, Kansas, United States

Flaget Memorial Hospital

🇺🇸

Bardstown, Kentucky, United States

Commonwealth Cancer Center-Corbin

🇺🇸

Corbin, Kentucky, United States

Saint Joseph Radiation Oncology Resource Center

🇺🇸

Lexington, Kentucky, United States

Saint Joseph Hospital East

🇺🇸

Lexington, Kentucky, United States

Saint Joseph London

🇺🇸

London, Kentucky, United States

Jewish Hospital

🇺🇸

Louisville, Kentucky, United States

Saints Mary and Elizabeth Hospital

🇺🇸

Louisville, Kentucky, United States

UofL Health Medical Center Northeast

🇺🇸

Louisville, Kentucky, United States

Jewish Hospital Medical Center South

🇺🇸

Shepherdsville, Kentucky, United States

Our Lady of the Lake Medical Oncology

🇺🇸

Baton Rouge, Louisiana, United States

Harold Alfond Center for Cancer Care

🇺🇸

Augusta, Maine, United States

Lafayette Family Cancer Center-EMMC

🇺🇸

Brewer, Maine, United States

MaineHealth Maine Medical Center- Scarborough

🇺🇸

Scarborough, Maine, United States

Greater Baltimore Medical Center

🇺🇸

Baltimore, Maryland, United States

National Institutes of Health Clinical Center

🇺🇸

Bethesda, Maryland, United States

University of Michigan Comprehensive Cancer Center

🇺🇸

Ann Arbor, Michigan, United States

Corewell Health Dearborn Hospital

🇺🇸

Dearborn, Michigan, United States

Corewell Health William Beaumont University Hospital

🇺🇸

Royal Oak, Michigan, United States

Doctors Cancer Center

🇵🇷

Manati, Puerto Rico

Instituto Oncologia Moderna Ponce

🇵🇷

Ponce, Puerto Rico

Corewell Health Beaumont Troy Hospital

🇺🇸

Troy, Michigan, United States

North Memorial Medical Health Center

🇺🇸

Robbinsdale, Minnesota, United States

Minnesota Oncology - Burnsville

🇺🇸

Burnsville, Minnesota, United States

Cambridge Medical Center

🇺🇸

Cambridge, Minnesota, United States

Fairview Southdale Hospital

🇺🇸

Edina, Minnesota, United States

Unity Hospital

🇺🇸

Fridley, Minnesota, United States

Fairview Clinics and Surgery Center Maple Grove

🇺🇸

Maple Grove, Minnesota, United States

Minnesota Oncology Hematology PA-Maplewood

🇺🇸

Maplewood, Minnesota, United States

Saint John's Hospital - Healtheast

🇺🇸

Maplewood, Minnesota, United States

Abbott-Northwestern Hospital

🇺🇸

Minneapolis, Minnesota, United States

Hennepin County Medical Center

🇺🇸

Minneapolis, Minnesota, United States

Health Partners Inc

🇺🇸

Minneapolis, Minnesota, United States

University of Minnesota/Masonic Cancer Center

🇺🇸

Minneapolis, Minnesota, United States

Monticello Cancer Center

🇺🇸

Monticello, Minnesota, United States

New Ulm Medical Center

🇺🇸

New Ulm, Minnesota, United States

Fairview Northland Medical Center

🇺🇸

Princeton, 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

Saint Francis Regional Medical Center

🇺🇸

Shakopee, Minnesota, United States

Lakeview Hospital

🇺🇸

Stillwater, Minnesota, United States

Ridgeview Medical Center

🇺🇸

Waconia, Minnesota, United States

Rice Memorial Hospital

🇺🇸

Willmar, Minnesota, United States

Minnesota Oncology Hematology PA-Woodbury

🇺🇸

Woodbury, Minnesota, United States

Fairview Lakes Medical Center

🇺🇸

Wyoming, Minnesota, United States

Saint Louis Cancer and Breast Institute-Ballwin

🇺🇸

Ballwin, Missouri, United States

Central Care Cancer Center - Bolivar

🇺🇸

Bolivar, Missouri, United States

Mercy Cancer Center - Cape Girardeau

🇺🇸

Cape Girardeau, Missouri, United States

Saint Francis Medical Center

🇺🇸

Cape Girardeau, Missouri, United States

Parkland Health Center - Farmington

🇺🇸

Farmington, Missouri, United States

MU Health Care Goldschmidt Cancer Center

🇺🇸

Jefferson City, Missouri, United States

Freeman Health System

🇺🇸

Joplin, Missouri, United States

Mercy Hospital Joplin

🇺🇸

Joplin, Missouri, United States

Mercy Clinic-Rolla-Cancer and Hematology

🇺🇸

Rolla, Missouri, United States

Phelps Health Delbert Day Cancer Institute

🇺🇸

Rolla, Missouri, United States

Heartland Regional Medical Center

🇺🇸

Saint Joseph, Missouri, United States

Saint Louis Cancer and Breast Institute-South City

🇺🇸

Saint Louis, Missouri, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Mercy Hospital South

🇺🇸

Saint Louis, Missouri, United States

Missouri Baptist Medical Center

🇺🇸

Saint Louis, Missouri, United States

Mercy Hospital Saint Louis

🇺🇸

Saint Louis, Missouri, United States

Fairfield Medical Center

🇺🇸

Lancaster, Ohio, United States

Sainte Genevieve County Memorial Hospital

🇺🇸

Sainte Genevieve, Missouri, United States

Mercy Hospital Springfield

🇺🇸

Springfield, Missouri, United States

BJC Outpatient Center at Sunset Hills

🇺🇸

Sunset Hills, Missouri, United States

Mercy Hospital Washington

🇺🇸

Washington, Missouri, United States

Community Hospital of Anaconda

🇺🇸

Anaconda, Montana, United States

Billings Clinic Cancer Center

🇺🇸

Billings, Montana, United States

Bozeman Health Deaconess Hospital

🇺🇸

Bozeman, Montana, United States

Benefis Sletten Cancer Institute

🇺🇸

Great Falls, Montana, United States

Great Falls Clinic

🇺🇸

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

🇺🇸

Grand Island, Nebraska, United States

CHI Health Good Samaritan

🇺🇸

Kearney, Nebraska, United States

Saint Elizabeth Regional Medical Center

🇺🇸

Lincoln, Nebraska, United States

Cancer Partners of Nebraska

🇺🇸

Lincoln, Nebraska, United States

Nebraska Methodist Hospital

🇺🇸

Omaha, Nebraska, United States

Alegent Health Immanuel Medical Center

🇺🇸

Omaha, Nebraska, United States

Alegent Health Bergan Mercy Medical Center

🇺🇸

Omaha, Nebraska, United States

Alegent Health Lakeside Hospital

🇺🇸

Omaha, Nebraska, United States

Creighton University Medical Center

🇺🇸

Omaha, Nebraska, United States

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

Midlands Community Hospital

🇺🇸

Papillion, Nebraska, United States

Women's Cancer Center of Nevada

🇺🇸

Las Vegas, Nevada, United States

Jersey Shore Medical Center

🇺🇸

Neptune, New Jersey, United States

University of New Mexico Cancer Center

🇺🇸

Albuquerque, New Mexico, United States

Memorial Medical Center-Las Cruces

🇺🇸

Las Cruces, New Mexico, United States

Presbyterian Rust Medical Center/Jorgensen Cancer Center

🇺🇸

Rio Rancho, New Mexico, United States

Northwell Health Imbert Cancer Center

🇺🇸

Bay Shore, New York, United States

Island Gynecologic Oncology

🇺🇸

Brightwaters, New York, United States

Roswell Park Cancer Institute

🇺🇸

Buffalo, New York, United States

Northwell Health/Center for Advanced Medicine

🇺🇸

Lake Success, New York, United States

State University of New York Upstate Medical University

🇺🇸

Syracuse, New York, United States

Dickstein Cancer Treatment Center

🇺🇸

White Plains, New York, United States

Southeastern Medical Oncology Center-Clinton

🇺🇸

Clinton, North Carolina, United States

Southeastern Medical Oncology Center-Goldsboro

🇺🇸

Goldsboro, North Carolina, United States

Southeastern Medical Oncology Center-Jacksonville

🇺🇸

Jacksonville, North Carolina, United States

Summa Health System - Akron Campus

🇺🇸

Akron, Ohio, United States

Aultman Alliance Community Hospital

🇺🇸

Alliance, Ohio, 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

Bethesda North Hospital

🇺🇸

Cincinnati, Ohio, United States

Delaware Health Center-Grady Cancer Center

🇺🇸

Delaware, Ohio, United States

Grady Memorial Hospital

🇺🇸

Delaware, Ohio, United States

Dublin Methodist Hospital

🇺🇸

Dublin, Ohio, United States

Central Ohio Breast and Endocrine Surgery

🇺🇸

Gahanna, Ohio, United States

Mount Carmel Grove City Hospital

🇺🇸

Grove City, Ohio, United States

OhioHealth Mansfield Hospital

🇺🇸

Mansfield, Ohio, United States

Marietta Memorial Hospital

🇺🇸

Marietta, Ohio, United States

OhioHealth Marion General Hospital

🇺🇸

Marion, 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

Knox Community Hospital

🇺🇸

Mount Vernon, Ohio, United States

Licking Memorial Hospital

🇺🇸

Newark, Ohio, United States

Newark Radiation Oncology

🇺🇸

Newark, Ohio, United States

Mercy Health - Perrysburg Hospital

🇺🇸

Perrysburg, Ohio, United States

Southern Ohio Medical Center

🇺🇸

Portsmouth, Ohio, United States

Mercy Health - Saint Vincent Hospital

🇺🇸

Toledo, Ohio, United States

Mercy Health - Saint Anne Hospital

🇺🇸

Toledo, Ohio, United States

University Hospitals Sharon Health Center

🇺🇸

Wadsworth, 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

Cancer Centers of Southwest Oklahoma Research

🇺🇸

Lawton, Oklahoma, 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

Saint Alphonsus Cancer Care Center-Baker City

🇺🇸

Baker City, Oregon, United States

Saint Charles Health System

🇺🇸

Bend, Oregon, United States

Clackamas Radiation Oncology Center

🇺🇸

Clackamas, Oregon, United States

Providence Cancer Institute Clackamas Clinic

🇺🇸

Clackamas, Oregon, United States

Bay Area Hospital

🇺🇸

Coos Bay, 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

Saint Charles Health System-Redmond

🇺🇸

Redmond, Oregon, United States

Legacy Meridian Park Hospital

🇺🇸

Tualatin, Oregon, United States

UPMC Hillman Cancer Center at Butler Health System

🇺🇸

Butler, Pennsylvania, United States

UPMC Hillman Cancer Center Erie

🇺🇸

Erie, Pennsylvania, United States

Paoli Memorial Hospital

🇺🇸

Paoli, Pennsylvania, United States

Thomas Jefferson University Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

Jefferson Torresdale Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

UPMC-Magee Womens Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

West Penn Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Cancer Institute (UPCI)

🇺🇸

Pittsburgh, Pennsylvania, United States

UPMC-Passavant Hospital

🇺🇸

Pittsburgh, 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

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

Saint Francis Hospital

🇺🇸

Federal Way, Washington, United States

Saint Francis Cancer Center

🇺🇸

Greenville, South Carolina, United States

Rapid City Regional Hospital

🇺🇸

Rapid City, South Dakota, United States

Bristol Regional Medical Center

🇺🇸

Bristol, Tennessee, United States

Ballad Health Cancer Care - Kingsport

🇺🇸

Kingsport, Tennessee, United States

Wellmont Holston Valley Hospital and Medical Center

🇺🇸

Kingsport, Tennessee, United States

Thompson Cancer Survival Center

🇺🇸

Knoxville, Tennessee, United States

Thompson Cancer Survival Center - West

🇺🇸

Knoxville, Tennessee, United States

Vanderbilt Breast Center at One Hundred Oaks

🇺🇸

Nashville, Tennessee, United States

Vanderbilt University/Ingram Cancer Center

🇺🇸

Nashville, Tennessee, United States

Saint Joseph Regional Cancer Center

🇺🇸

Bryan, Texas, United States

Parkland Memorial Hospital

🇺🇸

Dallas, Texas, United States

UT Southwestern/Simmons Cancer Center-Dallas

🇺🇸

Dallas, Texas, United States

Houston Methodist Hospital

🇺🇸

Houston, Texas, United States

Methodist Willowbrook Hospital

🇺🇸

Houston, Texas, United States

Houston Methodist West Hospital

🇺🇸

Houston, Texas, United States

Houston Methodist Sugar Land Hospital

🇺🇸

Sugar Land, Texas, United States

Houston Methodist The Woodlands Hospital

🇺🇸

The Woodlands, Texas, United States

Ballad Health Cancer Care - Bristol

🇺🇸

Bristol, Virginia, United States

Ballad Health Cancer Care - Norton

🇺🇸

Norton, Virginia, United States

Providence Regional Cancer System-Aberdeen

🇺🇸

Aberdeen, Washington, United States

PeaceHealth Saint Joseph Medical Center

🇺🇸

Bellingham, Washington, United States

Highline Medical Center-Main Campus

🇺🇸

Burien, Washington, United States

Providence Regional Cancer System-Centralia

🇺🇸

Centralia, Washington, United States

Swedish Cancer Institute-Edmonds

🇺🇸

Edmonds, Washington, United States

Saint Elizabeth Hospital

🇺🇸

Enumclaw, Washington, United States

Providence Regional Cancer Partnership

🇺🇸

Everett, Washington, United States

Swedish Cancer Institute-Issaquah

🇺🇸

Issaquah, Washington, United States

Kadlec Clinic Hematology and Oncology

🇺🇸

Kennewick, Washington, United States

Providence Regional Cancer System-Lacey

🇺🇸

Lacey, Washington, United States

Saint Clare Hospital

🇺🇸

Lakewood, Washington, United States

PeaceHealth Saint John Medical Center

🇺🇸

Longview, Washington, United States

Jefferson Healthcare

🇺🇸

Port Townsend, Washington, United States

Pacific Gynecology Specialists

🇺🇸

Seattle, Washington, United States

Swedish Medical Center-Ballard Campus

🇺🇸

Seattle, Washington, United States

Swedish Medical Center-Cherry Hill

🇺🇸

Seattle, Washington, United States

Swedish Medical Center-First Hill

🇺🇸

Seattle, Washington, United States

PeaceHealth United General Medical Center

🇺🇸

Sedro-Woolley, Washington, United States

Providence Regional Cancer System-Shelton

🇺🇸

Shelton, Washington, United States

Saint Michael Cancer Center

🇺🇸

Silverdale, Washington, United States

Franciscan Research Center-Northwest Medical Plaza

🇺🇸

Tacoma, Washington, United States

PeaceHealth Southwest Medical Center

🇺🇸

Vancouver, Washington, United States

Legacy Salmon Creek Hospital

🇺🇸

Vancouver, Washington, United States

Providence Saint Mary Regional Cancer Center

🇺🇸

Walla Walla, Washington, United States

Providence Regional Cancer System-Yelm

🇺🇸

Yelm, Washington, United States

West Virginia University Charleston Division

🇺🇸

Charleston, West Virginia, 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

Medical College of Wisconsin

🇺🇸

Milwaukee, 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

Saint Vincent Hospital Cancer Center at Sturgeon Bay

🇺🇸

Sturgeon Bay, Wisconsin, United States

ProHealth Waukesha Memorial Hospital

🇺🇸

Waukesha, Wisconsin, United States

UW Cancer Center at ProHealth Care

🇺🇸

Waukesha, Wisconsin, United States

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