Testing the Combination of Cediranib and Olaparib in Comparison to Each Drug Alone or Other Chemotherapy in Recurrent Platinum-Resistant Ovarian Cancer

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Active, not recruiting

CT.gov ID

NCT02502266

Collaborator

Canadian Cancer Trials Group (Other), NRG Oncology (Other)

562

Enrollment

400

Locations

Arms

88.8

Anticipated Duration (Months)

1.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized phase II/III trial studies how well cediranib maleate and olaparib work when given together or separately, and compares them to standard chemotherapy in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has returned (recurrent) after receiving chemotherapy with drugs that contain platinum (platinum-resistant) or continued to grow while being treated with platinum-based chemotherapy drugs (platinum-refractory). Cediranib maleate and olaparib may stop the growth of tumor cells by blocking enzymes needed for cell growth. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving cediranib maleate and olaparib together may cause more damage to cancer cells when compared to either drug alone or standard chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Clear Cell Adenocarcinoma Fallopian Tube Endometrioid Adenocarcinoma Fallopian Tube Serous Adenocarcinoma Fallopian Tube Transitional Cell Carcinoma Fallopian Tube Undifferentiated Carcinoma Ovarian Clear Cell Adenocarcinoma Ovarian Endometrioid Adenocarcinoma Ovarian Seromucinous Carcinoma Ovarian Serous Adenocarcinoma Ovarian Transitional Cell Carcinoma Ovarian Undifferentiated Carcinoma Primary Peritoneal Serous Adenocarcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma	Drug: Cediranib Drug: Cediranib Maleate Drug: Olaparib Drug: Paclitaxel Drug: Pegylated Liposomal Doxorubicin Hydrochloride Other: Questionnaire Administration Drug: Topotecan Drug: Topotecan Hydrochloride	Phase 2/Phase 3

Detailed Description

PRIMARY OBJECTIVES:

To assess the efficacy and identify (in)active arm(s) of the combination of cediranib maleate (cediranib) and olaparib, cediranib alone, olaparib alone, and physician's choice standard of care chemotherapy, as measured by progression-free survival (PFS) in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. (Phase II) II. To assess the efficacy of the combination of cediranib and olaparib, and cediranib monotherapy, as measured by overall survival (OS) and PFS, as compared to physician's choice standard of care chemotherapy in women with recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. (Phase III)

SECONDARY OBJECTIVES:

To assess the efficacy of the combination of cediranib and olaparib, cediranib alone, olaparib alone, and physician's choice standard of care chemotherapy, as measured by objective response rate (ORR: partial or complete response) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. (Phase II) II. To assess safety endpoints, as measured by frequency and severity of adverse events by Common Terminology Criteria for Adverse Events (CTCAE). (Phase II and Phase III) III. To assess the efficacy of the combination of cediranib and olaparib, and cediranib monotherapy, as measured by ORR as compared to physician's choice standard of care chemotherapy in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. (Phase III)

OBJECTIVES WITH INTEGRATED BIOMARKERS:

To assess correlation of homologous recombination deficiency (HRD) status, as assessed via BROCA-HR assay with response, as measured by PFS and ORR. (Phase II) II. To evaluate the prognostic and predictive role of circulating endothelial cells (CEC) on comparative effectiveness of targeted therapies and reference chemotherapy. (Phase II) III. To evaluate quality of life data compliance, as measured by the 9-item Disease Related Symptoms (DRS-9) subscale of the National Comprehensive Cancer Network (NCCN)-Functional Assessment of Cancer Therapy (FACT) Ovarian Symptom Index (NFOSI) for utilization and analysis in the Phase III study. (Phase II) IV. To assess correlation of HRD status, as assessed via BROCA-HR assay with response, as measured by OS, PFS and ORR. (Phase III) V. To evaluate the prognostic and predictive role of circulating endothelial cells (CEC) on comparative effectiveness of targeted therapies and reference chemotherapy. (Phase III) VI. To assess the effect on disease-related symptoms (DRS) as measured by the 9-item DRS-P subscale of the NCCN-FACT Ovarian Symptom Index-18 (NFOSI-18), of single agent cediranib and cediranib/olaparib combination, compared to standard chemotherapy, in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. (Phase

EXPLORATORY OBJECTIVES:

To assess exploratory biomarkers of potential HRD, including genomic scarring, BRCA1 methylation, BRCA1 protein expression, and mutations in NHEJ, and other genes that might modify HRD. (Phase II and Phase III) II. To evaluate the prognostic and predictive role of angiogenic biomarkers, as assessed by the Duke plasma angiome. (Phase II and Phase III) III. To assess the effect on secondary measures of quality of life, as assessed by the treatment side effects (TSE) and function/well-being (F/WB) subscales of the NFOSI-18, sensory neuropathy as measured by the FACT/GOG-Ntx-4, and health utility as measured by the EQ-5D, of single agent cediranib and cediranib/olaparib combination, compared to standard chemotherapy, in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. (Phase III)

OUTLINE:

PHASE II: Patients are randomized to 1 of 4 treatment arms.

ARM I (REFERENCE REGIMEN): Patients undergo physician's choice of standard of care chemotherapy, comprising either paclitaxel intravenously (IV) on days 1, 8, 15, and 22 every 28 days (Regimen I); pegylated liposomal doxorubicin hydrochloride IV on day 1 every 28 days (Regimen II); or topotecan hydrochloride IV on days 1, 8, and 15 every 28 days or days 1-5 every 21 days (Regimen III). Treatment continues in the absence of disease progression or unacceptable toxicity. No modification of the assigned regimens, such as additional drugs (gemcitabine, or bevacizumab) is allowed. (12/05/2016)

ARM II (CEDIRANIB MALEATE AND OLAPARIB): Patients receive cediranib maleate orally (PO) once daily (QD) and olaparib PO twice daily (BID). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM III (CEDIRANIB): Patients receive cediranib maleate PO daily continuously. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM IV (OLAPARIB): Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (In July 2018, the Data Monitoring Committee voted to exclude the olaparib alone regimen).

PHASE III: Patients are randomized to 1 of 3 treatment arms.

ARM I (REFERENCE REGIMEN): Patients undergo physician's choice standard of care chemotherapy as in Phase II Arm I. No modification of the assigned regimens, such as additional drugs (gemcitabine or bevacizumab) is allowed. (12/05/2016)

ARM II (CEDIRANIB AND OLAPARIB): Patients receive cediranib maleate PO and olaparib PO as in Phase II Arm II.

ARM III (SINGLE AGENT): Patients receive cediranib maleate PO as determined by the Phase II study. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

562 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase II/III Study of the Combination of Cediranib and Olaparib Compared to Cediranib or Olaparib Alone, or Standard of Care Chemotherapy in Women With Recurrent Platinum-Resistant or -Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (COCOS)

Actual Study Start Date :

Feb 5, 2016

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Phase II Arm I (reference regimen) Patients undergo physician's choice of standard of care chemotherapy, comprising either paclitaxel IV on days 1, 8, 15, and 22 every 28 days (Regimen I); pegylated liposomal doxorubicin hydrochloride IV on day 1 every 28 days (Regimen II); or topotecan hydrochloride IV on days 1, 8, and 15 every 28 days or days 1-5 every 21 days (Regimen III). Treatment continues in the absence of disease progression or unacceptable toxicity. No modification of the assigned regimens, such as additional drugs (gemcitabine, or bevacizumab) is allowed. (12/05/2016)	Drug: Paclitaxel Given IV Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat Drug: Pegylated Liposomal Doxorubicin Hydrochloride Given IV Other Names: ATI-0918 Caelyx Dox-SL Doxil Doxilen Doxorubicin HCl Liposomal Doxorubicin HCl Liposome Doxorubicin Hydrochloride Liposome Duomeisu Evacet LipoDox Lipodox 50 Liposomal Adriamycin Liposomal Doxorubicin Hydrochloride Liposomal-Encapsulated Doxorubicin Pegylated Doxorubicin HCl Liposome S-Liposomal Doxorubicin Stealth Liposomal Doxorubicin TLC D-99 Other: Questionnaire Administration Ancillary studies Drug: Topotecan Given IV Other Names: Hycamptamine Topotecan Lactone Drug: Topotecan Hydrochloride Given IV Other Names: Hycamptamine Hycamtin SKF S-104864-A Topotecan HCl topotecan hydrochloride (oral)
Experimental: Phase II Arm II (cediranib maleate, olaparib) Patients receive cediranib maleate PO QD and olaparib PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Cediranib Given PO Other Names: AZD2171 Drug: Cediranib Maleate Given PO Other Names: AZD2171 AZD2171 Maleate Recentin Drug: Olaparib Given PO Other Names: AZD 2281 AZD-2281 AZD2281 KU-0059436 Lynparza PARP Inhibitor AZD2281 Other: Questionnaire Administration Ancillary studies
Experimental: Phase II Arm III (cediranib maleate) Patients receive cediranib maleate PO daily continuously. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Cediranib Given PO Other Names: AZD2171 Drug: Cediranib Maleate Given PO Other Names: AZD2171 AZD2171 Maleate Recentin Other: Questionnaire Administration Ancillary studies
Experimental: Phase II Arm IV (olaparib) Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (In July 2018, the Data Monitoring Committee voted to exclude the olaparib alone regimen).	Drug: Olaparib Given PO Other Names: AZD 2281 AZD-2281 AZD2281 KU-0059436 Lynparza PARP Inhibitor AZD2281 Other: Questionnaire Administration Ancillary studies
Active Comparator: Phase III Arm I (reference regimen) Patients undergo physician's choice standard of care chemotherapy as in Phase II Arm I. No modification of the assigned regimens, such as additional drugs (gemcitabine or bevacizumab) is allowed. (12/05/2016)	Drug: Paclitaxel Given IV Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat Drug: Pegylated Liposomal Doxorubicin Hydrochloride Given IV Other Names: ATI-0918 Caelyx Dox-SL Doxil Doxilen Doxorubicin HCl Liposomal Doxorubicin HCl Liposome Doxorubicin Hydrochloride Liposome Duomeisu Evacet LipoDox Lipodox 50 Liposomal Adriamycin Liposomal Doxorubicin Hydrochloride Liposomal-Encapsulated Doxorubicin Pegylated Doxorubicin HCl Liposome S-Liposomal Doxorubicin Stealth Liposomal Doxorubicin TLC D-99 Other: Questionnaire Administration Ancillary studies Drug: Topotecan Given IV Other Names: Hycamptamine Topotecan Lactone Drug: Topotecan Hydrochloride Given IV Other Names: Hycamptamine Hycamtin SKF S-104864-A Topotecan HCl topotecan hydrochloride (oral)
Experimental: Phase III Arm II (cediranib maleate, olaparib) Patients receive cediranib maleate PO and olaparib PO as in Phase II Arm II.	Drug: Cediranib Given PO Other Names: AZD2171 Drug: Cediranib Maleate Given PO Other Names: AZD2171 AZD2171 Maleate Recentin Drug: Olaparib Given PO Other Names: AZD 2281 AZD-2281 AZD2281 KU-0059436 Lynparza PARP Inhibitor AZD2281 Other: Questionnaire Administration Ancillary studies
Experimental: Phase III Arm III (single-agent cediranib maleate) Patients receive cediranib maleate PO as determined by the Phase II study. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Cediranib Given PO Other Names: AZD2171 Drug: Cediranib Maleate Given PO Other Names: AZD2171 AZD2171 Maleate Recentin Other: Questionnaire Administration Ancillary studies

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) (Phase II and Phase III) [Time from study enrollment to the onset of progression as determined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST) criteria, or death due to any cause, whichever occurs first, assessed up to 5 years]
Progression-free survival will be assessed. The primary analysis of PFS will be assessed using a proportional hazards model with patients analyzed according to the arm to which they were randomized, regardless of whether treatment is received.
Overall survival (OS) (Phase III) [Time from study enrollment to death due to any cause, assessed up to 5 years]
Overall survival will be evaluated. To allow for better understanding of time to subsequent therapy and OS, patients on experimental study drug(s) or standard chemotherapy arm will be followed after progression, with data capture to include the date of initiation of the subsequent therapy, detailed information on the type of subsequent therapy received, and time to progression on the subsequent therapy.

Secondary Outcome Measures

Objective response rate (partial or complete response) (Phase II and Phase III) [Up to 5 years]
Objective response rate will be defined by RECIST 1.1.
Incidence of adverse events (Phase II and Phase III) [Up to 5 years]
Frequency and severity of adverse events measured by Common Terminology Criteria for Adverse Events version 4.0

Other Outcome Measures

Patient-reported scores of disease-related symptoms [Up to 5 years]
Measured by the 9-item Disease Related Symptoms (DRS-9) subscale of the National Comprehensive Cancer Network (NCCN)-Functional Assessment of Cancer Therapy (FACT) Ovarian Symptom Index (NFOSI-18).
Gene mutations assessed BROCA-HR [Up to 5 years]
A single proportional hazards model will be used to estimate the treatment hazard ratios (and variances) for each of the experimental treatments selected for phase III evaluation relative to the reference treatment (chemotherapy) group. The model will include adjustments for prior platinum-free interval, prior bevacizumab treatment, age at study enrollment, randomly assigned study treatment and BROCA-HR status. The estimated hazard ratio(s) for BROCA-HR and the corresponding confidence intervals will be depicted with a forest plot, and assessed for qualitative interaction(s).
Change in circulating endothelial cell levels [Baseline up to 5 years]
A proportional hazards model will be used to assess a linear association between the change in circulating endothelial cell values and the log relative hazard of death within each treatment group. Sensitivity analyses will include known prognostic factors in the model. A plot of the martingale residuals or estimated relative hazards by change in circulating endothelial cell quintiles will be used to qualitatively assess the assumption of a linear relationship between the change in circulating endothelial cell values and the log relative hazard.
Biomarkers in plasma angiome [Up to 5 years]
A proportional hazards model will be used to assess whether the pretreatment values of any of these analytes have a prognostic association with overall survival. The model will include clinical covariates: age, performance status, and the randomly assigned study treatment. Proportional hazards models will be used to assess the relationship between patients' analyte values and log hazard. A proportional hazards model will be used to assess the potential predictive associations between analytes, treatment and survival.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must have histologically or cytologically confirmed ovarian cancer, peritoneal cancer or fallopian tube cancer and must have a histological diagnosis of either serous or endometrioid cancer based on local histopathological findings; both endometrioid and serous histology should be high-grade for eligibility of non-mutation carriers; patients with clear cell, mixed epithelial, undifferentiated carcinoma, or transitional cell carcinoma histologies are also eligible, provided that the patient has a known deleterious germline BRCA1 or BRCA2 mutation identified through testing at a clinical laboratory
Note: Due to the long acceptance of BRCA testing through Myriad, Myriad testing will be accepted; if testing for BRCA is done by other organizations, documentation from a qualified medical professional (e.g., ovarian cancer specialty physician involved in the field, high risk genetics physician, genetics counselor) listing the mutation and confirming that the laboratory results showed a recognized germ line deleterious BRCA 1 or BRCA 2 mutation or BRCA rearrangement is required; a copy of Myriad or other BRCA mutational analysis (positive or variants of unknown significance [VUS] or negative) reports will be requested but not required for study enrollment
Patients should have recurrent platinum-resistant or- refractory disease - defined as disease that has progressed by imaging while receiving platinum or had recurrence within 6 months of the last receipt of platinum-based chemotherapy; rising CA125 only is not considered as platinum-resistant or refractory disease
Phase II study: measurable disease by RECIST 1.1 criteria; if archival tumor sample is not available tumor sample from fresh biopsy is acceptable
Phase III study: 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 cancer antigen [CA]125 >= 2 x upper limit of normal [ULN])
No more than 3 prior treatment regimens (including primary therapy; no more than 1 prior non-platinum based therapy in the platinum-resistant/-refractory setting); hormonal therapies used as single agents (i.e. tamoxifen, aromatase inhibitors) will not count towards this line limit
Patients may not have had a prior anti-angiogenic agent in the recurrent setting; prior use of bevacizumab in the upfront or upfront maintenance setting is allowed
Patients may not have previously received a PARP-inhibitor
Patient must have provided study specific informed consent prior to study entry
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 or 2
Absolute neutrophil count >= 1,500/mcL
Platelets >= 100,000/mcL
Hemoglobin >= 10 g/dL
Total bilirubin within =< 1.5 times the upper limit of normal (ULN) institutional limits
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN; if intrahepatic liver metastases are present, AST and ALT must be =< 5 times institutional ULN
Creatinine =< 1.5 x the institutional ULN
Urine protein: creatinine ratio urine protein creatinine (UPC) of =< 1 OR less than or equal to 2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart; UPC is the preferred test; patients with 2+ proteinuria on dipstick must also have a 24-hour urine collection demonstrating protein of =< 500 mg over 24 hours
Toxicities of prior therapy (excepting alopecia) should be resolved to less than or equal to grade 1 as per CTCAE; patients with long-standing stable grade 2 neuropathy may be considered after discussion with the study chair.
Adequately controlled blood pressure (systolic blood pressure [SBP] =< 140; diastolic blood pressure [DBP] =< 90 mmHg) on 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 starting study; 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; blood pressure cuffs will be provided to patients randomized to cediranib alone and the combination of olaparib and cediranib arms
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction and thyroid-stimulating hormone (TSH) within normal limits
Able to swallow and retain oral medications and without gastrointestinal (GI) illnesses that would preclude absorption of cediranib or olaparib
Age >= 18 years
Cediranib has been shown to terminate fetal development in the rat, as expected for a process dependent on VEGF signaling; for this reason, women of child-bearing potential must have a negative pregnancy test prior to study entry; women of child-bearing potential must agree to use two reliable forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 weeks after cediranib discontinuation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Olaparib adversely affects embryofetal survival and development in the rat; for this reason, women of child-bearing potential must have a negative pregnancy test prior to study entry; women of child-bearing potential must agree to use must agree to use two reliable forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 months after the last dose of olaparib; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Exclusion Criteria:

Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) of starting treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; patients may not have had hormonal therapy within 2 weeks prior to entering the study; patients receiving raloxifene for bone health as per Food and Drug Administration (FDA) indication may remain on raloxifene absent other drug interactions
Any other investigational agents within the past 4 weeks
Prior treatment affecting the VEGF/VEGFR pathway or the angiopoietin pathway in the recurrent setting, including but not limited to thalidomide, bevacizumab, sunitinib, sorafenib, pazopanib, cediranib, nintedanib, and trebananib; bevacizumab used in the upfront setting in conjunction with chemotherapy and/or as maintenance to treat newly diagnosed disease will be allowed
Prior use of PARP-inhibitors
CA-125 only disease without Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measurable or otherwise evaluable disease
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting cediranib
Current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowel obstruction within 3 months prior to starting study drugs
History of intra-abdominal abscess within the past 3 months
History of gastrointestinal perforation; patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired or has healed, there has been no evidence of fistula for at least 6 months, and patient is deemed to be at low risk of recurrent fistula
Dependency on IV hydration or total parenteral nutrition (TPN)
Any concomitant or prior invasive malignancies with the following curatively treated exceptions:
Treated limited stage basal cell or squamous cell carcinoma of the skin
Carcinoma in situ of the breast or cervix
Primary endometrial cancer meeting the following conditions: stage not greater than IA, grade 1 or 2, no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous/serous, clear cell, or other Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions
Prior cancer treated with a curative intent with no evidence of recurrent disease 5 years following diagnosis and judged by the investigator to be at low risk of recurrence
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 drug
Patients with any of the following:
History of myocardial infarction within six months
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
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
Clinical significant peripheral vascular disease or vascular disease (aortic aneurysm or aortic dissection)
Evidence of coagulopathy or bleeding diathesis; therapeutic anticoagulation for prior thromboembolic events is permitted
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)
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
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
Known human immunodeficiency virus (HIV)-positive individuals are ineligible because of the potential for pharmacokinetic interactions with cediranib or olaparib; in addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy
Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible
Strong inhibitors and inducers of UGT/PgP should be used with caution
Pregnant women are excluded from this study because cediranib and olaparib are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with cediranib and olaparib, breastfeeding should be discontinued if the mother is treated with cediranib or olaparib; these potential risks may also apply to other agents used in this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	Alaska Women's Cancer Care	Anchorage	Alaska	United States	99508
3	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
4	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
5	Sutter Auburn Faith Hospital	Auburn	California	United States	95602
6	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
7	Mercy San Juan Medical Center	Carmichael	California	United States	95608
8	Mercy Cancer Center - Elk Grove	Elk Grove	California	United States	95758
9	Marin Cancer Care Inc	Greenbrae	California	United States	94904
10	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
11	Palo Alto Medical Foundation-Camino Division	Mountain View	California	United States	94040
12	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California	United States	94040
13	Kaiser Permanente-Oakland	Oakland	California	United States	94611
14	Palo Alto Medical Foundation Health Care	Palo Alto	California	United States	94301
15	Mercy Cancer Center - Rocklin	Rocklin	California	United States	95765
16	Sutter Roseville Medical Center	Roseville	California	United States	95661
17	Kaiser Permanente Downtown Commons	Sacramento	California	United States	95814
18	Mercy Cancer Center - Sacramento	Sacramento	California	United States	95816
19	Sutter Medical Center Sacramento	Sacramento	California	United States	95816
20	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
21	Kaiser Permanente - Sacramento	Sacramento	California	United States	95825
22	California Pacific Medical Center-Pacific Campus	San Francisco	California	United States	94115
23	Kaiser Permanente-San Francisco	San Francisco	California	United States	94115
24	UCSF Medical Center-Mission Bay	San Francisco	California	United States	94158
25	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California	United States	93401
26	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
27	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California	United States	95065
28	Sutter Pacific Medical Foundation	Santa Rosa	California	United States	95403
29	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California	United States	94086
30	Kaiser Permanente-Vallejo	Vallejo	California	United States	94589
31	Kaiser Permanente-Walnut Creek	Walnut Creek	California	United States	94596
32	Woodland Memorial Hospital	Woodland	California	United States	95695
33	University of Colorado Hospital	Aurora	Colorado	United States	80045
34	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
35	UCHealth Memorial Hospital Central	Colorado Springs	Colorado	United States	80909
36	Kaiser Permanente-Franklin	Denver	Colorado	United States	80205
37	Rocky Mountain Cancer Centers-Rose	Denver	Colorado	United States	80220
38	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
39	UCHealth Highlands Ranch Hospital	Highlands Ranch	Colorado	United States	80129
40	Kaiser Permanente-Rock Creek	Lafayette	Colorado	United States	80026
41	Kaiser Permanente-Lone Tree	Lone Tree	Colorado	United States	80124
42	Danbury Hospital	Danbury	Connecticut	United States	06810
43	Smilow Cancer Hospital Care Center-Fairfield	Fairfield	Connecticut	United States	06824
44	Hartford Hospital	Hartford	Connecticut	United States	06102
45	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
46	Middlesex Hospital	Middletown	Connecticut	United States	06457
47	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
48	Yale University	New Haven	Connecticut	United States	06520
49	Norwalk Hospital	Norwalk	Connecticut	United States	06856
50	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut	United States	06611
51	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
52	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
53	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
54	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
55	University of Florida Health Science Center - Gainesville	Gainesville	Florida	United States	32610
56	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
57	Orlando Health Cancer Institute	Orlando	Florida	United States	32806
58	Sarasota Memorial Hospital	Sarasota	Florida	United States	34239
59	Emory University Hospital Midtown	Atlanta	Georgia	United States	30308
60	Piedmont Hospital	Atlanta	Georgia	United States	30309
61	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia	United States	30322
62	Northside Hospital	Atlanta	Georgia	United States	30342
63	Augusta University Medical Center	Augusta	Georgia	United States	30912
64	WellStar Cobb Hospital	Austell	Georgia	United States	30106
65	WellStar Health System Inc	Marietta	Georgia	United States	30060
66	Wellstar Kennestone Hospital	Marietta	Georgia	United States	30060
67	WellStar North Fulton Hospital	Roswell	Georgia	United States	30076
68	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
69	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia	United States	31405
70	WellStar Vinings Health Park	Smyrna	Georgia	United States	30080
71	Queen's Medical Center	Honolulu	Hawaii	United States	96813
72	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
73	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
74	Saint Luke's Cancer Institute - Boise	Boise	Idaho	United States	83712
75	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho	United States	83619
76	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho	United States	83642
77	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho	United States	83686
78	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
79	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
80	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
81	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
82	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
83	Northwestern University	Chicago	Illinois	United States	60611
84	John H Stroger Jr Hospital of Cook County	Chicago	Illinois	United States	60612
85	Rush University Medical Center	Chicago	Illinois	United States	60612
86	UChicago Medicine Comprehensive Cancer Center - Saint Joseph Hospital	Chicago	Illinois	United States	60657
87	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
88	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
89	Crossroads Cancer Center	Effingham	Illinois	United States	62401
90	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
91	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
92	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
93	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois	United States	60134
94	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois	United States	60026
95	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois	United States	60035
96	Sudarshan K Sharma MD Limited-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
97	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
98	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
99	Cancer Care Center of O'Fallon	O'Fallon	Illinois	United States	62269
100	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
101	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
102	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
103	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
104	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
105	Springfield Clinic	Springfield	Illinois	United States	62702
106	Memorial Medical Center	Springfield	Illinois	United States	62781
107	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois	United States	60555
108	Midwestern Regional Medical Center	Zion	Illinois	United States	60099
109	Parkview Regional Medical Center	Fort Wayne	Indiana	United States	46845
110	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
111	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
112	Reid Health	Richmond	Indiana	United States	47374
113	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
114	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
115	Mercy Cancer Center-West Lakes	Clive	Iowa	United States	50325
116	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
117	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
118	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
119	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
120	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
121	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
122	Mercy Medical Center-West Lakes	West Des Moines	Iowa	United States	50266
123	Associates In Womens Health	Wichita	Kansas	United States	67208
124	Ascension Via Christi Hospitals Wichita	Wichita	Kansas	United States	67214
125	Saint Elizabeth Healthcare Edgewood	Edgewood	Kentucky	United States	41017
126	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
127	Hematology/Oncology Clinic PLLC	Baton Rouge	Louisiana	United States	70809
128	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
129	Woman's Hospital	Baton Rouge	Louisiana	United States	70817
130	Women's Cancer Care-Covington	Covington	Louisiana	United States	70433
131	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
132	Eastern Maine Medical Center	Bangor	Maine	United States	04401
133	Lafayette Family Cancer Center-EMMC	Brewer	Maine	United States	04412
134	Maine Medical Center- Scarborough Campus	Scarborough	Maine	United States	04074
135	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
136	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland	United States	21237
137	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
138	UM Upper Chesapeake Medical Center	Bel Air	Maryland	United States	21014
139	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892
140	TidalHealth Richard A Henson Cancer Institute	Ocean Pines	Maryland	United States	21811
141	TidalHealth Peninsula Regional	Salisbury	Maryland	United States	21801
142	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
143	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
144	UMass Memorial Medical Center - Memorial Division	Worcester	Massachusetts	United States	01605
145	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
146	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
147	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan	United States	48183
148	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan	United States	48038
149	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
150	Henry Ford Hospital	Detroit	Michigan	United States	48202
151	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49829
152	Weisberg Cancer Treatment Center	Farmington Hills	Michigan	United States	48334
153	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
154	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
155	Sparrow Hospital	Lansing	Michigan	United States	48912
156	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
157	Munson Medical Center	Traverse City	Michigan	United States	49684
158	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan	United States	48322
159	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota	United States	56601
160	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
161	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
162	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
163	Mayo Clinic Health Systems-Mankato	Mankato	Minnesota	United States	56001
164	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota	United States	55369
165	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
166	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
167	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
168	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
169	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
170	Regions Hospital	Saint Paul	Minnesota	United States	55101
171	United Hospital	Saint Paul	Minnesota	United States	55102
172	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
173	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
174	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
175	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
176	University of Missouri - Ellis Fischel	Columbia	Missouri	United States	65212
177	Mercy Hospital Joplin	Joplin	Missouri	United States	64804
178	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
179	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
180	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
181	CoxHealth South Hospital	Springfield	Missouri	United States	65807
182	Billings Clinic Cancer Center	Billings	Montana	United States	59101
183	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
184	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
185	CHI Health Saint Francis	Grand Island	Nebraska	United States	68803
186	CHI Health Good Samaritan	Kearney	Nebraska	United States	68847
187	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
188	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
189	Alegent Health Lakeside Hospital	Omaha	Nebraska	United States	68130
190	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89106
191	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
192	Norris Cotton Cancer Center-Nashua	Nashua	New Hampshire	United States	03063
193	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
194	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
195	The Cancer Institute of New Jersey Hamilton	Hamilton	New Jersey	United States	08690
196	Morristown Medical Center	Morristown	New Jersey	United States	07960
197	Jersey Shore Medical Center	Neptune	New Jersey	United States	07753
198	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
199	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey	United States	08876
200	Overlook Hospital	Summit	New Jersey	United States	07902
201	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey	United States	08043
202	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
203	Southwest Gynecologic Oncology Associates Inc	Albuquerque	New Mexico	United States	87106
204	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico	United States	88011
205	Women's Cancer Care Associates LLC	Albany	New York	United States	12208
206	Montefiore Medical Center-Einstein Campus	Bronx	New York	United States	10461
207	State University of New York Downstate Medical Center	Brooklyn	New York	United States	11203
208	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
209	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
210	University of Rochester	Rochester	New York	United States	14642
211	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
212	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
213	Dickstein Cancer Treatment Center	White Plains	New York	United States	10601
214	AdventHealth Infusion Center Asheville	Asheville	North Carolina	United States	28803
215	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
216	AdventHealth Infusion Center Haywood	Clyde	North Carolina	United States	28721
217	Duke University Medical Center	Durham	North Carolina	United States	27710
218	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina	United States	27534
219	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
220	AdventHealth Hendersonville	Hendersonville	North Carolina	United States	28792
221	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina	United States	28546
222	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina	United States	28374
223	Duke Raleigh Hospital	Raleigh	North Carolina	United States	27609
224	New Hanover Regional Medical Center/Zimmer Cancer Center	Wilmington	North Carolina	United States	28401
225	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
226	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
227	Sanford Broadway Medical Center	Fargo	North Dakota	United States	58122
228	Sanford Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
229	Cleveland Clinic Akron General	Akron	Ohio	United States	44307
230	Aultman Health Foundation	Canton	Ohio	United States	44710
231	Miami Valley Hospital South	Centerville	Ohio	United States	45459
232	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio	United States	45219
233	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio	United States	45220
234	TriHealth Cancer Institute-Westside	Cincinnati	Ohio	United States	45247
235	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
236	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
237	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
238	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
239	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
240	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
241	Grandview Hospital	Dayton	Ohio	United States	45405
242	Orion Cancer Care	Findlay	Ohio	United States	45840
243	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
244	ProMedica Flower Hospital	Sylvania	Ohio	United States	43560
245	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio	United States	43606
246	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio	United States	45069
247	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio	United States	45433
248	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
249	Cancer Treatment Centers of America	Tulsa	Oklahoma	United States	74133
250	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
251	Saint Charles Health System	Bend	Oregon	United States	97701
252	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
253	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon	United States	97210
254	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
255	Jefferson Abington Hospital	Abington	Pennsylvania	United States	19001
256	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania	United States	18015
257	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
258	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
259	Ephrata Cancer Center	Ephrata	Pennsylvania	United States	17522
260	Ephrata Community Hospital	Ephrata	Pennsylvania	United States	17522
261	Adams Cancer Center	Gettysburg	Pennsylvania	United States	17325
262	Cherry Tree Cancer Center	Hanover	Pennsylvania	United States	17331
263	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania	United States	17109
264	Sechler Family Cancer Center	Lebanon	Pennsylvania	United States	17042
265	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania	United States	17837
266	Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301
267	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
268	West Penn Hospital	Pittsburgh	Pennsylvania	United States	15224
269	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania	United States	18840
270	Reading Hospital	West Reading	Pennsylvania	United States	19611
271	Wexford Health and Wellness Pavilion	Wexford	Pennsylvania	United States	15090
272	UPMC Susquehanna	Williamsport	Pennsylvania	United States	17701
273	Asplundh Cancer Pavilion	Willow Grove	Pennsylvania	United States	19090
274	Lankenau Medical Center	Wynnewood	Pennsylvania	United States	19096
275	WellSpan Health-York Hospital	York	Pennsylvania	United States	17403
276	Women and Infants Hospital	Providence	Rhode Island	United States	02905
277	AnMed Health Cancer Center	Anderson	South Carolina	United States	29621
278	Gibbs Cancer Center-Gaffney	Gaffney	South Carolina	United States	29341
279	Saint Francis Hospital	Greenville	South Carolina	United States	29601
280	Saint Francis Cancer Center	Greenville	South Carolina	United States	29607
281	Gibbs Cancer Center-Pelham	Greer	South Carolina	United States	29651
282	South Carolina Cancer Specialists PC	Hilton Head Island	South Carolina	United States	29926-3827
283	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
284	MGC Hematology Oncology-Union	Union	South Carolina	United States	29379
285	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
286	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota	United States	57104
287	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
288	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
289	Ballad Health Cancer Care - Kingsport	Kingsport	Tennessee	United States	37660
290	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee	United States	37660
291	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
292	Thompson Cancer Survival Center - West	Knoxville	Tennessee	United States	37932
293	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
294	Parkland Memorial Hospital	Dallas	Texas	United States	75235
295	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
296	Houston Methodist Hospital	Houston	Texas	United States	77030
297	Methodist Willowbrook Hospital	Houston	Texas	United States	77070
298	Houston Methodist Sugar Land Hospital	Sugar Land	Texas	United States	77479
299	Intermountain Medical Center	Murray	Utah	United States	84107
300	Saint George Regional Medical Center	Saint George	Utah	United States	84770
301	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah	United States	84106
302	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
303	South Jordan Health Center	South Jordan	Utah	United States	84009
304	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont	United States	05602
305	University of Vermont Medical Center	Burlington	Vermont	United States	05401
306	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405
307	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
308	VCU Massey Cancer Center at Stony Point	Richmond	Virginia	United States	23235
309	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
310	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
311	Swedish Cancer Institute-Edmonds	Edmonds	Washington	United States	98026
312	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
313	Skagit Regional Health Cancer Care Center	Mount Vernon	Washington	United States	98274
314	Skagit Valley Hospital	Mount Vernon	Washington	United States	98274
315	Pacific Gynecology Specialists	Seattle	Washington	United States	98104
316	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
317	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
318	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
319	University of Washington Medical Center - Northwest	Seattle	Washington	United States	98133
320	Women's Cancer Center of Seattle	Seattle	Washington	United States	98133
321	University of Washington Medical Center - Montlake	Seattle	Washington	United States	98195
322	Legacy Salmon Creek Hospital	Vancouver	Washington	United States	98686
323	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
324	West Virginia University Charleston Division	Charleston	West Virginia	United States	25304
325	Edwards Comprehensive Cancer Center	Huntington	West Virginia	United States	25701
326	Monongalia Hospital	Morgantown	West Virginia	United States	26505
327	West Virginia University Healthcare	Morgantown	West Virginia	United States	26506
328	Ascension Saint Elizabeth Hospital	Appleton	Wisconsin	United States	54915
329	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin	United States	53105
330	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
331	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin	United States	54701
332	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin	United States	54937
333	Aurora Health Care Germantown Health Center	Germantown	Wisconsin	United States	53022
334	Aurora Cancer Care-Grafton	Grafton	Wisconsin	United States	53024
335	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
336	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
337	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
338	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin	United States	53142
339	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
340	Marshfield Clinic - Ladysmith Center	Ladysmith	Wisconsin	United States	54848
341	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792
342	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin	United States	54143
343	Saint Vincent Hospital Cancer Center at Marinette	Marinette	Wisconsin	United States	54143
344	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin	United States	54449
345	Ascension Columbia Saint Mary's Hospital Ozaukee	Mequon	Wisconsin	United States	53097
346	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin	United States	53209
347	Ascension Columbia Saint Mary's Hospital - Milwaukee	Milwaukee	Wisconsin	United States	53211
348	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
349	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
350	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53233
351	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
352	ProHealth D N Greenwald Center	Mukwonago	Wisconsin	United States	53149
353	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin	United States	53066
354	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin	United States	54154
355	Ascension Mercy Hospital	Oshkosh	Wisconsin	United States	54904
356	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
357	Aurora Cancer Care-Racine	Racine	Wisconsin	United States	53406
358	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin	United States	54868
359	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
360	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
361	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin	United States	54482
362	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235-1495
363	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066
364	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin	United States	54241
365	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin	United States	53188
366	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin	United States	53188
367	Marshfield Clinic-Wausau Center	Wausau	Wisconsin	United States	54401
368	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin	United States	53226
369	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227
370	Marshfield Medical Center - Weston	Weston	Wisconsin	United States	54476
371	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
372	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
373	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
374	Royal Victoria Regional Health Centre	Barrie	Ontario	Canada	L4M 6M2
375	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
376	Kingston Health Sciences Centre	Kingston	Ontario	Canada	K7L 2V7
377	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
378	Algoma District Cancer Program Sault Area Hospital	Sault Ste Marie	Ontario	Canada	P6B 0A8
379	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
380	University Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
381	CIUSSSEMTL-Hopital Maisonneuve-Rosemont	Montreal	Quebec	Canada	H1T 2M4
382	CHUM - Hopital Notre-Dame	Montreal	Quebec	Canada	H2L 4M1
383	CHUM - Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec	Canada	H2X 3E4
384	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
385	CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)	Quebec City	Quebec	Canada	G1R 2J6
386	Ehime University Hospital	Toon	Ehime	Japan	791-0295
387	Hokkaido University Hospital	Sapporo	Hokkaido	Japan	060-8648
388	Kagoshima City Hospital	Kagoshima City	Kagoshima	Japan	890-8760
389	The Cancer Institute Hospital Of JFCR	Koto-ku	Tokyo	Japan	135-8550
390	Kindai University	Osaka		Japan	589 8511
391	Saitama Medical University International Medical Center	Saitama		Japan	350-1298
392	National Cancer Center Hospital	Tokyo		Japan	104 0045
393	Keimyung University-Dongsan Medical Center	Dalseo-gu	Daegu	Korea, Republic of	42601
394	Seoul National University Bundang Hospital	Seongnam City	Kyeonggi-do	Korea, Republic of	463-707
395	Gachon University Gil Hospital	Incheon		Korea, Republic of	405-760
396	Asan Medical Center	Seoul		Korea, Republic of	05505
397	Gangnam Severance Hospital	Seoul		Korea, Republic of	06273
398	Kyung Hee University Hospital at Gangdong	Seoul		Korea, Republic of	134-727
399	Korea Cancer Center Hospital	Seoul		Korea, Republic of	139-706
400	Centro Comprensivo de Cancer de UPR	San Juan		Puerto Rico	00927