Testing the Combination of Cediranib and Olaparib in Comparison to Each Drug Alone or Other Chemotherapy in Recurrent Platinum-Resistant Ovarian Cancer
Fallopian Tube Clear Cell Adenocarcinoma, Fallopian Tube Endometrioid Adenocarcinoma, Fallopian Tube Serous Adenocarcinoma
About this trial
This is an interventional treatment trial for Fallopian Tube Clear Cell Adenocarcinoma
Eligibility Criteria
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 (12/05/2016); 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 (12/05/2016)
- Phase II study: measurable disease by RECIST 1.1 criteria; if archival tumor sample is not available tumor sample from fresh biopsy is acceptable (12/05/2016)
- 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 (12/05/2016)
- 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 (12/05/2016)
- Platelets >= 100,000/mcL (12/05/2016)
- Hemoglobin >= 10 g/dL (12/05/2016)
- Total bilirubin within =< 1.5 times the upper limit of normal (ULN) institutional limits (12/05/2016)
- 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 (12/05/2016)
- Creatinine =< 1.5 x the institutional ULN (12/05/2016)
- 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 (12/05/2016)
- 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 (12/05/2016)
- Adequately controlled thyroid function, with no symptoms of thyroid dysfunction and thyroid-stimulating hormone (TSH) within normal limits (12/05/2016)
- 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 (12/05/2016)
- 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 (12/05/2016)
- 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 (12/05/2016)
- 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 (12/05/2016)
- 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 (12/05/2016)
- 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
Sites / Locations
- University of Alabama at Birmingham Cancer Center
- Alaska Women's Cancer Care
- Providence Alaska Medical Center
- University of Arkansas for Medical Sciences
- Sutter Auburn Faith Hospital
- Alta Bates Summit Medical Center-Herrick Campus
- Mercy San Juan Medical Center
- Mercy Cancer Center - Elk Grove
- Marin Cancer Care Inc
- UC San Diego Moores Cancer Center
- Palo Alto Medical Foundation-Camino Division
- Palo Alto Medical Foundation-Gynecologic Oncology
- Kaiser Permanente-Oakland
- Palo Alto Medical Foundation Health Care
- Mercy Cancer Center - Rocklin
- Sutter Roseville Medical Center
- Kaiser Permanente Downtown Commons
- Mercy Cancer Center - Sacramento
- Sutter Medical Center Sacramento
- University of California Davis Comprehensive Cancer Center
- Kaiser Permanente - Sacramento
- California Pacific Medical Center-Pacific Campus
- Kaiser Permanente-San Francisco
- UCSF Medical Center-Mission Bay
- Pacific Central Coast Health Center-San Luis Obispo
- Kaiser Permanente Medical Center - Santa Clara
- Palo Alto Medical Foundation-Santa Cruz
- Sutter Pacific Medical Foundation
- Palo Alto Medical Foundation-Sunnyvale
- Kaiser Permanente-Vallejo
- Kaiser Permanente-Walnut Creek
- Woodland Memorial Hospital
- UCHealth University of Colorado Hospital
- Penrose-Saint Francis Healthcare
- UCHealth Memorial Hospital Central
- Kaiser Permanente-Franklin
- Rocky Mountain Cancer Centers-Rose
- Poudre Valley Hospital
- UCHealth Highlands Ranch Hospital
- Kaiser Permanente-Rock Creek
- Kaiser Permanente-Lone Tree
- Danbury Hospital
- Smilow Cancer Hospital Care Center-Fairfield
- Hartford Hospital
- Smilow Cancer Hospital Care Center at Saint Francis
- Middlesex Hospital
- The Hospital of Central Connecticut
- Yale University
- Norwalk Hospital
- Smilow Cancer Hospital Care Center-Trumbull
- Helen F Graham Cancer Center
- Medical Oncology Hematology Consultants PA
- Christiana Care Health System-Christiana Hospital
- Sibley Memorial Hospital
- University of Florida Health Science Center - Gainesville
- Mount Sinai Medical Center
- Orlando Health Cancer Institute
- Sarasota Memorial Hospital
- Emory University Hospital Midtown
- Piedmont Hospital
- Emory University Hospital/Winship Cancer Institute
- Northside Hospital
- Augusta University Medical Center
- WellStar Cobb Hospital
- WellStar Health System Inc
- Wellstar Kennestone Hospital
- WellStar North Fulton Hospital
- Memorial Health University Medical Center
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- WellStar Vinings Health Park
- Queen's Medical Center
- Kapiolani Medical Center for Women and Children
- Saint Alphonsus Cancer Care Center-Boise
- Saint Luke's Cancer Institute - Boise
- Saint Luke's Cancer Institute - Fruitland
- Saint Luke's Cancer Institute - Meridian
- Saint Luke's Cancer Institute - Nampa
- Rush - Copley Medical Center
- Illinois CancerCare-Bloomington
- Illinois CancerCare-Canton
- Illinois CancerCare-Carthage
- Centralia Oncology Clinic
- Northwestern University
- John H Stroger Jr Hospital of Cook County
- Rush University Medical Center
- UChicago Medicine Comprehensive Cancer Center - Saint Joseph Hospital
- Cancer Care Specialists of Illinois - Decatur
- Decatur Memorial Hospital
- Crossroads Cancer Center
- Illinois CancerCare-Eureka
- NorthShore University HealthSystem-Evanston Hospital
- Illinois CancerCare-Galesburg
- Northwestern Medicine Cancer Center Delnor
- NorthShore University HealthSystem-Glenbrook Hospital
- NorthShore University HealthSystem-Highland Park Hospital
- Sudarshan K Sharma MD Limited-Gynecologic Oncology
- Illinois CancerCare-Kewanee Clinic
- Illinois CancerCare-Macomb
- Cancer Care Center of O'Fallon
- Illinois CancerCare-Ottawa Clinic
- Illinois CancerCare-Pekin
- Illinois CancerCare-Peoria
- Illinois CancerCare-Peru
- Illinois CancerCare-Princeton
- Springfield Clinic
- Memorial Medical Center
- Northwestern Medicine Cancer Center Warrenville
- Midwestern Regional Medical Center
- Parkview Regional Medical Center
- Indiana University/Melvin and Bren Simon Cancer Center
- Ascension Saint Vincent Indianapolis Hospital
- Reid Health
- Memorial Hospital of South Bend
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Iowa Methodist Medical Center
- Medical Oncology and Hematology Associates-Des Moines
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- University of Iowa/Holden Comprehensive Cancer Center
- Siouxland Regional Cancer Center
- Mercy Medical Center-West Lakes
- Associates In Womens Health
- Ascension Via Christi Hospitals Wichita
- Saint Elizabeth Healthcare Edgewood
- University of Kentucky/Markey Cancer Center
- Hematology/Oncology Clinic PLLC
- Mary Bird Perkins Cancer Center
- Woman's Hospital
- Women's Cancer Care-Covington
- Ochsner Medical Center Jefferson
- Eastern Maine Medical Center
- Lafayette Family Cancer Center-EMMC
- Maine Medical Center- Scarborough Campus
- Greater Baltimore Medical Center
- MedStar Franklin Square Medical Center/Weinberg Cancer Institute
- Johns Hopkins University/Sidney Kimmel Cancer Center
- UM Upper Chesapeake Medical Center
- National Institutes of Health Clinical Center
- TidalHealth Richard A Henson Cancer Institute
- TidalHealth Peninsula Regional
- Brigham and Women's Hospital
- Dana-Farber Cancer Institute
- UMass Memorial Medical Center - Memorial Division
- Saint Joseph Mercy Hospital
- University of Michigan Comprehensive Cancer Center
- Henry Ford Cancer Institute-Downriver
- Henry Ford Macomb Hospital-Clinton Township
- Wayne State University/Karmanos Cancer Institute
- Henry Ford Hospital
- Green Bay Oncology - Escanaba
- Weisberg Cancer Treatment Center
- Spectrum Health at Butterworth Campus
- West Michigan Cancer Center
- Sparrow Hospital
- Saint Joseph Mercy Oakland
- Munson Medical Center
- Henry Ford West Bloomfield Hospital
- Sanford Joe Lueken Cancer Center
- Fairview Ridges Hospital
- Mercy Hospital
- Fairview Southdale Hospital
- Mayo Clinic Health Systems-Mankato
- Fairview Clinics and Surgery Center Maple Grove
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- University of Minnesota/Masonic Cancer Center
- Mayo Clinic in Rochester
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Saint Francis Regional Medical Center
- Minnesota Oncology Hematology PA-Woodbury
- University of Mississippi Medical Center
- Saint Francis Medical Center
- MU Health - University Hospital/Ellis Fischel Cancer Center
- Mercy Hospital Joplin
- Barnes-Jewish Hospital
- Washington University School of Medicine
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Billings Clinic Cancer Center
- Bozeman Deaconess Hospital
- Benefis Healthcare- Sletten Cancer Institute
- CHI Health Saint Francis
- CHI Health Good Samaritan
- Nebraska Methodist Hospital
- Alegent Health Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- Women's Cancer Center of Nevada
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Dartmouth Cancer Center - Nashua
- Cooper Hospital University Medical Center
- Hackensack University Medical Center
- The Cancer Institute of New Jersey Hamilton
- Morristown Medical Center
- Jersey Shore Medical Center
- Rutgers Cancer Institute of New Jersey
- Robert Wood Johnson University Hospital Somerset
- Overlook Hospital
- MD Anderson Cancer Center at Cooper-Voorhees
- University of New Mexico Cancer Center
- Southwest Gynecologic Oncology Associates Inc
- Memorial Medical Center - Las Cruces
- Women's Cancer Care Associates LLC
- Montefiore Medical Center-Einstein Campus
- State University of New York Downstate Medical Center
- Roswell Park Cancer Institute
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- University of Rochester
- Stony Brook University Medical Center
- State University of New York Upstate Medical University
- Dickstein Cancer Treatment Center
- AdventHealth Infusion Center Asheville
- UNC Lineberger Comprehensive Cancer Center
- AdventHealth Infusion Center Haywood
- Duke University Medical Center
- Southeastern Medical Oncology Center-Goldsboro
- Margaret R Pardee Memorial Hospital
- AdventHealth Hendersonville
- Southeastern Medical Oncology Center-Jacksonville
- FirstHealth of the Carolinas-Moore Regional Hospital
- Duke Raleigh Hospital
- Novant Health New Hanover Regional Medical Center
- Wake Forest University Health Sciences
- Sanford Bismarck Medical Center
- Sanford Broadway Medical Center
- Sanford Roger Maris Cancer Center
- Cleveland Clinic Akron General
- Aultman Health Foundation
- Miami Valley Hospital South
- University of Cincinnati Cancer Center-UC Medical Center
- Good Samaritan Hospital - Cincinnati
- TriHealth Cancer Institute-Westside
- MetroHealth Medical Center
- Cleveland Clinic Cancer Center/Fairview Hospital
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- Riverside Methodist Hospital
- The Mark H Zangmeister Center
- Grandview Hospital
- Orion Cancer Care
- Hillcrest Hospital Cancer Center
- ProMedica Flower Hospital
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- University of Cincinnati Cancer Center-West Chester
- Wright-Patterson Medical Center
- University of Oklahoma Health Sciences Center
- Cancer Treatment Centers of America
- Oklahoma Cancer Specialists and Research Institute-Tulsa
- Saint Charles Health System
- Legacy Mount Hood Medical Center
- Legacy Good Samaritan Hospital and Medical Center
- Legacy Meridian Park Hospital
- Jefferson Abington Hospital
- Saint Luke's University Hospital-Bethlehem Campus
- Bryn Mawr Hospital
- Geisinger Medical Center
- Ephrata Cancer Center
- Ephrata Community Hospital
- Adams Cancer Center
- Cherry Tree Cancer Center
- UPMC Pinnacle Cancer Center/Community Osteopathic Campus
- Sechler Family Cancer Center
- Geisinger Medical Oncology-Lewisburg
- Paoli Memorial Hospital
- University of Pennsylvania/Abramson Cancer Center
- West Penn Hospital
- Guthrie Medical Group PC-Robert Packer Hospital
- Reading Hospital
- Wexford Health and Wellness Pavilion
- UPMC Susquehanna
- Asplundh Cancer Pavilion
- Lankenau Medical Center
- WellSpan Health-York Hospital
- Women and Infants Hospital
- AnMed Health Cancer Center
- Gibbs Cancer Center-Gaffney
- Saint Francis Hospital
- Saint Francis Cancer Center
- Gibbs Cancer Center-Pelham
- South Carolina Cancer Specialists PC
- Spartanburg Medical Center
- MGC Hematology Oncology-Union
- Rapid City Regional Hospital
- Sanford Cancer Center Oncology Clinic
- Avera Cancer Institute
- Sanford USD Medical Center - Sioux Falls
- Ballad Health Cancer Care - Kingsport
- Wellmont Holston Valley Hospital and Medical Center
- Thompson Cancer Survival Center
- Thompson Cancer Survival Center - West
- Vanderbilt University/Ingram Cancer Center
- Parkland Memorial Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- Houston Methodist Hospital
- Methodist Willowbrook Hospital
- Houston Methodist Sugar Land Hospital
- Intermountain Medical Center
- Saint George Regional Medical Center
- Utah Cancer Specialists-Salt Lake City
- Huntsman Cancer Institute/University of Utah
- South Jordan Health Center
- Central Vermont Medical Center/National Life Cancer Treatment
- University of Vermont Medical Center
- University of Vermont and State Agricultural College
- University of Virginia Cancer Center
- VCU Massey Cancer Center at Stony Point
- Virginia Commonwealth University/Massey Cancer Center
- PeaceHealth Saint Joseph Medical Center
- Swedish Cancer Institute-Edmonds
- Kadlec Clinic Hematology and Oncology
- Skagit Regional Health Cancer Care Center
- Skagit Valley Hospital
- Pacific Gynecology Specialists
- FHCC South Lake Union
- Fred Hutchinson Cancer Research Center
- Swedish Medical Center-First Hill
- University of Washington Medical Center - Northwest
- Women's Cancer Center of Seattle
- University of Washington Medical Center - Montlake
- Legacy Salmon Creek Hospital
- Wenatchee Valley Hospital and Clinics
- West Virginia University Charleston Division
- Edwards Comprehensive Cancer Center
- Monongalia Hospital
- West Virginia University Healthcare
- Ascension Saint Elizabeth Hospital
- Aurora Cancer Care-Southern Lakes VLCC
- Marshfield Clinic-Chippewa Center
- Marshfield Clinic Cancer Center at Sacred Heart
- Aurora Health Center-Fond du Lac
- Aurora Health Care Germantown Health Center
- Aurora Cancer Care-Grafton
- Saint Vincent Hospital Cancer Center Green Bay
- Saint Vincent Hospital Cancer Center at Saint Mary's
- Aurora BayCare Medical Center
- Aurora Cancer Care-Kenosha South
- Gundersen Lutheran Medical Center
- Marshfield Clinic - Ladysmith Center
- University of Wisconsin Carbone Cancer Center
- Aurora Bay Area Medical Group-Marinette
- Saint Vincent Hospital Cancer Center at Marinette
- Marshfield Medical Center-Marshfield
- Ascension Columbia Saint Mary's Hospital Ozaukee
- Aurora Cancer Care-Milwaukee
- Ascension Columbia Saint Mary's Hospital - Milwaukee
- Aurora Saint Luke's Medical Center
- Medical College of Wisconsin
- Aurora Sinai Medical Center
- Marshfield Clinic-Minocqua Center
- ProHealth D N Greenwald Center
- ProHealth Oconomowoc Memorial Hospital
- Saint Vincent Hospital Cancer Center at Oconto Falls
- Ascension Mercy Hospital
- Vince Lombardi Cancer Clinic - Oshkosh
- Aurora Cancer Care-Racine
- Marshfield Medical Center-Rice Lake
- Vince Lombardi Cancer Clinic-Sheboygan
- Ascension Saint Michael's Hospital
- Marshfield Medical Center-River Region at Stevens Point
- Saint Vincent Hospital Cancer Center at Sturgeon Bay
- Aurora Medical Center in Summit
- Vince Lombardi Cancer Clinic-Two Rivers
- ProHealth Waukesha Memorial Hospital
- UW Cancer Center at ProHealth Care
- Marshfield Clinic-Wausau Center
- Aurora Cancer Care-Milwaukee West
- Aurora West Allis Medical Center
- Marshfield Medical Center - Weston
- Marshfield Clinic - Wisconsin Rapids Center
- Tom Baker Cancer Centre
- Cross Cancer Institute
- Royal Victoria Regional Health Centre
- Juravinski Cancer Centre at Hamilton Health Sciences
- Kingston Health Sciences Centre
- London Regional Cancer Program
- Algoma District Cancer Program Sault Area Hospital
- Odette Cancer Centre- Sunnybrook Health Sciences Centre
- University Health Network-Princess Margaret Hospital
- CIUSSSEMTL-Hopital Maisonneuve-Rosemont
- CHUM - Hopital Notre-Dame
- CHUM - Centre Hospitalier de l'Universite de Montreal
- Jewish General Hospital
- CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
- Ehime University Hospital
- Hokkaido University Hospital
- Kagoshima City Hospital
- The Cancer Institute Hospital Of JFCR
- Kindai University
- Saitama Medical University International Medical Center
- National Cancer Center Hospital
- Keimyung University-Dongsan Medical Center
- Seoul National University Bundang Hospital
- Gachon University Gil Hospital
- Asan Medical Center
- Gangnam Severance Hospital
- Kyung Hee University Hospital at Gangdong
- Korea Cancer Center Hospital
- Centro Comprensivo de Cancer de UPR
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Active Comparator
Experimental
Experimental
Experimental
Active Comparator
Experimental
Experimental
Phase II Arm I (reference regimen)
Phase II Arm II (cediranib maleate, olaparib)
Phase II Arm III (cediranib maleate)
Phase II Arm IV (olaparib)
Phase III Arm I (reference regimen)
Phase III Arm II (cediranib maleate, olaparib)
Phase III Arm III (single-agent cediranib maleate)
Patients undergo physician's choice of standard of care chemotherapy, comprising either paclitaxel IV over 60 minutes on days 1, 8, 15, and 22 every 28 days (Regimen I); pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 every 28 days (Regimen II); or topotecan hydrochloride IV over 30 minutes 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. Patients also undergo CT and MRI throughout the study. (12/05/2016)
Patients receive cediranib maleate PO QD and olaparib PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the study.
Patients receive cediranib maleate PO daily continuously. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the study.
Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the study. (In July 2018, the Data Monitoring Committee voted to exclude the olaparib alone 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. Patients also undergo CT and MRI throughout the study. (12/05/2016)
Patients receive cediranib maleate PO and olaparib PO as in Phase II Arm II. Patients also undergo CT and MRI throughout the study.
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. Patients also undergo CT and MRI throughout the study.