Purpose

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 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. Drugs used in chemotherapy 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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Female
Accepts Healthy Volunteers
No

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
  • 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 must be actively 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
  • 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

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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)
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • 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 Liposome
    • doxorubicin hydrochloride liposome
    • Duomeisu
    • Evacet
    • LipoDox
    • 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 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 and olaparib PO as determined from an ongoing Phase I study. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Cediranib Maleate
    Given PO
    Other names:
    • AZD2171
    • AZD2171 Maleate
    • Recentin
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Olaparib
    Given PO
    Other names:
    • 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. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Cediranib Maleate
    Given PO
    Other names:
    • AZD2171
    • AZD2171 Maleate
    • Recentin
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Questionnaire Administration
    Ancillary studies
Experimental
Phase II Arm IV (olaparib)
Patients receive olaparib PO BID on days 1-28. Courses 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).
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Olaparib
    Given PO
    Other names:
    • 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)
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • 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 Liposome
    • doxorubicin hydrochloride liposome
    • Duomeisu
    • Evacet
    • LipoDox
    • 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 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 Maleate
    Given PO
    Other names:
    • AZD2171
    • AZD2171 Maleate
    • Recentin
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Olaparib
    Given PO
    Other names:
    • 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. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Cediranib Maleate
    Given PO
    Other names:
    • AZD2171
    • AZD2171 Maleate
    • Recentin
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Questionnaire Administration
    Ancillary studies

Recruiting Locations

Alaska Women's Cancer Care
Anchorage, Alaska 99508
Contact:
Site Public Contact
412-339-5294
Roster@nrgoncology.org

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205
Contact:
Site Public Contact
501-686-8274

Mercy San Juan Medical Center
Carmichael, California 95608
Contact:
Site Public Contact
916-556-3301
OncologyResearch@DignityHealth.org

Marin Cancer Care Inc
Greenbrae, California 94904
Contact:
Site Public Contact
415-925-5000
info@marinspecialtycare.com

Palo Alto Medical Foundation-Camino Division
Mountain View, California 94040
Contact:
Site Public Contact
415-209-2686
bernicl@sutterhealth.org

Palo Alto Medical Foundation-Gynecologic Oncology
Mountain View, California 94040
Contact:
Site Public Contact
415-209-2686
bernicl@sutterhealth.org

Sutter Roseville Medical Center
Roseville, California 95661
Contact:
Site Public Contact
415-209-2686
bernicl@sutterhealth.org

Mercy Cancer Center - Sacramento
Sacramento, California 95816
Contact:
Site Public Contact
916-556-3301
OncologyResearch@DignityHealth.org

Sutter Medical Center Sacramento
Sacramento, California 95816
Contact:
Site Public Contact
916-454-6500
cancerinfo@sutterhealth.org

California Pacific Medical Center-Pacific Campus
San Francisco, California 94115
Contact:
Site Public Contact
415-209-2686
bernicl@sutterhealth.org

Palo Alto Medical Foundation-Santa Cruz
Santa Cruz, California 95065
Contact:
Site Public Contact
415-209-2686
bernicl@sutterhealth.org

Palo Alto Medical Foundation-Sunnyvale
Sunnyvale, California 94086
Contact:
Site Public Contact
415-209-2686
bernicl@sutterhealth.org

Woodland Memorial Hospital
Woodland, California 95695
Contact:
Site Public Contact
916-556-3301
OncologyResearch@DignityHealth.org

University of Colorado Hospital
Aurora, Colorado 80045
Contact:
Site Public Contact
720-848-0650

UCHealth Memorial Hospital Central
Colorado Springs, Colorado 80909
Contact:
Site Public Contact
719-365-2406

Kaiser Permanente-Franklin
Denver, Colorado 80205
Contact:
Site Public Contact
303-764-5056
josh.b.gordon@nsmtp.kp.org

Poudre Valley Hospital
Fort Collins, Colorado 80524
Contact:
Site Public Contact
970-297-6150

Kaiser Permanente-Rock Creek
Lafayette, Colorado 80026
Contact:
Site Public Contact
303-764-5056
josh.b.gordon@nsmtp.kp.org

Kaiser Permanente-Lone Tree
Lone Tree, Colorado 80124
Contact:
Site Public Contact
303-764-5056
josh.b.gordon@nsmtp.kp.org

Hartford Hospital
Hartford, Connecticut 06102
Contact:
Site Public Contact
860-545-5363

The Hospital of Central Connecticut
New Britain, Connecticut 06050
Contact:
Site Public Contact
860-224-5660

University of Florida Health Science Center - Gainesville
Gainesville, Florida 32610
Contact:
Site Public Contact
352-273-8010
cancer-center@ufl.edu

Emory University Hospital Midtown
Atlanta, Georgia 30308
Contact:
Site Public Contact
888-946-7447

Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia 30322
Contact:
Site Public Contact
404-778-1868

Memorial Health University Medical Center
Savannah, Georgia 31404
Contact:
Site Public Contact
912-350-7887
clayter1@memorialhealth.com

Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
Savannah, Georgia 31405
Contact:
Site Public Contact
412-339-5294
Roster@nrgoncology.org

Kapiolani Medical Center for Women and Children
Honolulu, Hawaii 96826
Contact:
Site Public Contact
808-983-6090

Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho 83706
Contact:
Site Public Contact
734-712-3671
stephanie.couch@stjoeshealth.org

Rush University Medical Center
Chicago, Illinois 60612
Contact:
Site Public Contact
312-942-5498
clinical_trials@rush.edu

Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois 62526
Contact:
Site Public Contact
217-876-4740

Crossroads Cancer Center
Effingham, Illinois 62401
Contact:
Site Public Contact
217-876-4740
rhamrick@dmhhs.org

NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois 60201
Contact:
Site Public Contact
847-570-2109

NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois 60026
Contact:
Site Public Contact
847-570-2109

Sudarshan K Sharma MD Limited-Gynecologic Oncology
Hinsdale, Illinois 60521
Contact:
Site Public Contact
630-856-6757

Springfield Clinic
Springfield, Illinois 62702
Contact:
Site Public Contact
800-444-7541

Cancer Care Specialists of Illinois-Swansea
Swansea, Illinois 62226
Contact:
Site Public Contact
217-876-4740
rhamrick@dmhhs.org

Parkview Regional Medical Center
Fort Wayne, Indiana 46845
Contact:
Site Public Contact
877-784-4673

Reid Health
Richmond, Indiana 47374
Contact:
Site Public Contact
937-775-1350
som_dcop@wright.edu

Memorial Hospital of South Bend
South Bend, Indiana 46601
Contact:
Site Public Contact
800-284-7370

Iowa Methodist Medical Center
Des Moines, Iowa 50309
Contact:
Site Public Contact
515-241-6727

University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa 52242
Contact:
Site Public Contact
800-237-1225

Siouxland Regional Cancer Center
Sioux City, Iowa 51101
Contact:
Site Public Contact
712-252-9326
HoopingarnerT@jencc.com

Associates In Womens Health
Wichita, Kansas 67208
Contact:
Site Public Contact
316-268-5374
Keisha.humphries@ascension.org

Via Christi Regional Medical Center
Wichita, Kansas 67214
Contact:
Site Public Contact
800-362-0070
Keisha.humphries@ascension.org

Women's Cancer Care-Covington
Covington, Louisiana 70433
Contact:
Site Public Contact
412-339-5294
Roster@nrgoncology.org

Ochsner Medical Center Jefferson
New Orleans, Louisiana 70121
Contact:
Site Public Contact
504-703-8712
Gregory.Johnstone@ochsner.org

Eastern Maine Medical Center
Bangor, Maine 04401
Contact:
Site Public Contact
207-973-4274

Lafayette Family Cancer Center-EMMC
Brewer, Maine 04412
Contact:
Site Public Contact
800-987-3005

Maine Medical Center- Scarborough Campus
Scarborough, Maine 04074
Contact:
Site Public Contact
207-396-8090
wrighd@mmc.org

Greater Baltimore Medical Center
Baltimore, Maryland 21204
Contact:
Site Public Contact
443-849-3706

National Institutes of Health Clinical Center
Bethesda, Maryland 20892
Contact:
Site Public Contact
800-411-1222

Peninsula Regional Medical Center
Salisbury, Maryland 21801
Contact:
Site Public Contact
866-922-6237

Dana-Farber Cancer Institute
Boston, Massachusetts 02215
Contact:
Site Public Contact
877-442-3324

Saint Joseph Mercy Hospital
Ann Arbor, Michigan 48106
Contact:
Site Public Contact
734-712-3671
stephanie.couch@stjoeshealth.org

Wayne State University/Karmanos Cancer Institute
Detroit, Michigan 48201
Contact:
Site Public Contact
313-576-9790
ctoadmin@karmanos.org

Green Bay Oncology - Escanaba
Escanaba, Michigan 49829
Contact:
Site Public Contact
920-433-8889
Christy.Gilchrist@hshs.org

Weisberg Cancer Treatment Center
Farmington Hills, Michigan 48334
Contact:
Site Public Contact
313-576-9790
ctoadmin@karmanos.org

Spectrum Health at Butterworth Campus
Grand Rapids, Michigan 49503
Contact:
Site Public Contact
616-391-1230
crcwm-regulatory@crcwm.org

West Michigan Cancer Center
Kalamazoo, Michigan 49007
Contact:
Site Public Contact
616-391-1230
crcwm-regulatory@crcwm.org

Sparrow Hospital
Lansing, Michigan 48912
Contact:
Site Public Contact
734-712-3671
stephanie.couch@stjoeshealth.org

Munson Medical Center
Traverse City, Michigan 49684
Contact:
Site Public Contact
616-391-1230
crcwm-regulatory@crcwm.org

Sanford Joe Lueken Cancer Center
Bemidji, Minnesota 56601
Contact:
Site Public Contact
218-333-5000
OncologyClinicalTrialsFargo@sanfordhealth.org

Fairview-Southdale Hospital
Edina, Minnesota 55435
Contact:
Site Public Contact
952-993-1517
mmcorc@healthpartners.com

Fairview Maple Grove Medical Center
Maple Grove, Minnesota 55369
Contact:
Site Public Contact
952-993-1517
mmcorc@healthpartners.com

University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota 55455
Contact:
Site Public Contact
412-339-5294
Roster@nrgoncology.org

Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota 55416
Contact:
Site Public Contact
952-993-1517
mmcorc@healthpartners.com

Regions Hospital
Saint Paul, Minnesota 55101
Contact:
Site Public Contact
952-993-1517
mmcorc@healthpartners.com

United Hospital
Saint Paul, Minnesota 55102
Contact:
Site Public Contact
952-993-1517
mmcorc@healthpartners.com

Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota 55125
Contact:
Site Public Contact
952-993-1517
mmcorc@healthpartners.com

University of Mississippi Medical Center
Jackson, Mississippi 39216
Contact:
Site Public Contact
601-815-6700

Saint Francis Medical Center
Cape Girardeau, Missouri 63703
Contact:
Site Public Contact
573-334-2230
sfmc@sfmc.net

CHI Health Saint Francis
Grand Island, Nebraska 68803
Contact:
Site Public Contact
308-398-6518
clinicaltrials@sfmc-gi.org

Nebraska Methodist Hospital
Omaha, Nebraska 68114
Contact:
Site Public Contact
402-354-5144

Women's Cancer Center of Nevada
Las Vegas, Nevada 89169
Contact:
Site Public Contact
412-339-5294
Roster@nrgoncology.org

Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire 03756
Contact:
Site Public Contact
800-639-6918
cancer.research.nurse@dartmouth.edu

Cooper Hospital University Medical Center
Camden, New Jersey 08103
Contact:
Site Public Contact
856-325-6757

University of New Mexico Cancer Center
Albuquerque, New Mexico 87102
Contact:
Site Public Contact
505-925-0366
LByatt@nmcca.org

Southwest Gynecologic Oncology Associates Inc
Albuquerque, New Mexico 87106
Contact:
Site Public Contact
505-272-0530
RDraper@nmcca.org

Memorial Medical Center - Las Cruces
Las Cruces, New Mexico 88011
Contact:
Site Public Contact
575-556-6545
Kim.Hoffman@lpnt.net

Montefiore Medical Center-Einstein Campus
Bronx, New York 10461
Contact:
Site Public Contact
718-379-6866
aaraiza@montefiore.org

State University of New York Upstate Medical University
Syracuse, New York 13210
Contact:
Site Public Contact
315-464-5476

Southeastern Medical Oncology Center-Goldsboro
Goldsboro, North Carolina 27534
Contact:
Site Public Contact
919-587-9077
ecooke@cancersmoc.com

Margaret R Pardee Memorial Hospital
Hendersonville, North Carolina 28791
Contact:
Site Public Contact
828-696-4716
karen.morris@unchealth.unc.edu

Southeastern Medical Oncology Center-Jacksonville
Jacksonville, North Carolina 28546
Contact:
Site Public Contact
910-353-0824
ecooke@cancersmoc.com

FirstHealth of the Carolinas-Moore Regional Hospital
Pinehurst, North Carolina 28374
Contact:
Site Public Contact
910-715-3500
jcwilliams@firsthealth.org

Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157
Contact:
Site Public Contact
336-713-6771

Sanford Bismarck Medical Center
Bismarck, North Dakota 58501
Contact:
Site Public Contact
701-323-5760
OncologyClinicalTrialsFargo@sanfordhealth.org

Sanford Broadway Medical Center
Fargo, North Dakota 58122
Contact:
Site Public Contact
701-323-5760
OncologyClinicalTrialsFargo@sanfordhealth.org

Sanford Roger Maris Cancer Center
Fargo, North Dakota 58122
Contact:
Site Public Contact
701-234-6161
OncologyClinicalTrialsFargo@sanfordhealth.org

Good Samaritan Hospital - Cincinnati
Cincinnati, Ohio 45220
Contact:
Site Public Contact
308-398-6518
clinicaltrials@sfmc-gi.org

Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio 44111
Contact:
Site Public Contact
866-223-8100
CancerAnswer@ccf.org

Cleveland Clinic Foundation
Cleveland, Ohio 44195
Contact:
Site Public Contact
866-223-8100
CancerAnswer@ccf.org

Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43210
Contact:
Site Public Contact
800-293-5066
Jamesline@osumc.edu

Riverside Methodist Hospital
Columbus, Ohio 43214
Contact:
Site Public Contact
614-566-4475
sheree@columbusccop.org

The Mark H Zangmeister Center
Columbus, Ohio 43219
Contact:
Site Public Contact
614-488-2118
sheree@columbusccop.org

Orion Cancer Care
Findlay, Ohio 45840
Contact:
Site Public Contact
937-775-1350
som_dcop@wright.edu

Hillcrest Hospital Cancer Center
Mayfield Heights, Ohio 44124
Contact:
Site Public Contact
866-223-8100
CancerAnswer@ccf.org

ProMedica Flower Hospital
Sylvania, Ohio 43560
Contact:
Site Public Contact
419-824-1842

University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
Contact:
Site Public Contact
405-271-8777
ou-clinical-trials@ouhsc.edu

Oklahoma Cancer Specialists and Research Institute-Tulsa
Tulsa, Oklahoma 74146
Contact:
Site Public Contact
918-505-3200

Geisinger Medical Center
Danville, Pennsylvania 17822
Contact:
Site Public Contact
570-271-5251
HemonCCTrials@geisinger.edu

Ephrata Cancer Center
Ephrata, Pennsylvania 17522
Contact:
Site Public Contact
717-721-4840

Sechler Family Cancer Center
Lebanon, Pennsylvania 17042
Contact:
Site Public Contact
717-741-8303
doxenberg@wellspan.org

Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania 17837
Contact:
Site Public Contact
570-374-8555
HemonCCTrials@geisinger.edu

Paoli Memorial Hospital
Paoli, Pennsylvania 19301
Contact:
Site Public Contact
484-476-2649
turzoe@mlhs.org

West Penn Hospital
Pittsburgh, Pennsylvania 15224
Contact:
Site Public Contact
412-578-5000

Guthrie Medical Group PC-Robert Packer Hospital
Sayre, Pennsylvania 18840
Contact:
Site Public Contact
800-836-0388

Reading Hospital
West Reading, Pennsylvania 19611
Contact:
Site Public Contact
610-988-9323

Lankenau Medical Center
Wynnewood, Pennsylvania 19096
Contact:
Site Public Contact
484-476-2649
turzoe@mlhs.org

WellSpan Health-York Hospital
York, Pennsylvania 17403
Contact:
Site Public Contact
877-441-7957

Women and Infants Hospital
Providence, Rhode Island 02905
Contact:
Site Public Contact
401-274-1122

Saint Francis Hospital
Greenville, South Carolina 29601
Contact:
Site Public Contact
864-603-6213
meissa_beckman@bshsi.org

Saint Francis Cancer Center
Greenville, South Carolina 29607
Contact:
Site Public Contact
864-603-6213
meissa_beckman@bshsi.org

South Carolina Cancer Specialists PC
Hilton Head Island, South Carolina 29926-3827
Contact:
Site Public Contact
912-819-5704
underberga@sjchs.org

Rapid City Regional Hospital
Rapid City, South Dakota 57701
Contact:
Site Public Contact
605-716-3982
research@rcrh.org

Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota 57104
Contact:
Site Public Contact
605-312-3320
OncologyClinicTrialsSF@sanfordhealth.org

Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota 57117-5134
Contact:
Site Public Contact
605-312-3320
OncologyClinicalTrialsSF@SanfordHealth.org

Regional Cancer Center at Indian Path Community Hospital
Kingsport, Tennessee 37660
Contact:
Site Public Contact
423-578-8538
Justin.reynolds@balladhealth.org

Wellmont Holston Valley Hospital and Medical Center
Kingsport, Tennessee 37660
Contact:
Site Public Contact
423-578-8538
justin.reynolds@wellmont.org

Thompson Cancer Survival Center
Knoxville, Tennessee 37916
Contact:
Site Public Contact
865-331-1812

Thompson Cancer Survival Center - West
Knoxville, Tennessee 37932
Contact:
Site Public Contact
865-331-1812

Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee 37232
Contact:
Site Public Contact
800-811-8480

The Methodist Hospital System
Houston, Texas 77030
Contact:
Site Public Contact
713-790-2700

Houston Methodist Sugar Land Hospital
Sugar Land, Texas 77479
Contact:
Site Public Contact
281-242-2873

Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah 84112
Contact:
Site Public Contact
888-424-2100
cancerinfo@hci.utah.edu

University of Virginia Cancer Center
Charlottesville, Virginia 22908
Contact:
Site Public Contact
434-243-6303
PAS9E@virginia.edu

Swedish Medical Center-First Hill
Seattle, Washington 98122-4307
Contact:
Site Public Contact
206-215-3086
PCRC-NCORP@Swedish.org

West Virginia University Charleston Division
Charleston, West Virginia 25304
Contact:
Site Public Contact
304-388-9944

Edwards Comprehensive Cancer Center
Huntington, West Virginia 25701
Contact:
Site Public Contact
304-399-6617

Aurora Cancer Care-Southern Lakes VLCC
Burlington, Wisconsin 53105
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

Aurora Health Center-Fond du Lac
Fond Du Lac, Wisconsin 54937
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

Aurora Health Care Germantown Health Center
Germantown, Wisconsin 53022
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

Aurora Cancer Care-Grafton
Grafton, Wisconsin 53024
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin 54301
Contact:
Site Public Contact
920-433-8889
Christy.Gilchrist@hshs.org

Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin 54303
Contact:
Site Public Contact
412-339-5294
Roster@nrgoncology.org

Aurora BayCare Medical Center
Green Bay, Wisconsin 54311
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

Aurora Cancer Care-Kenosha South
Kenosha, Wisconsin 53142
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

Aurora Bay Area Medical Group-Marinette
Marinette, Wisconsin 54143
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

Saint Vincent Hospital Cancer Center at Marinette
Marinette, Wisconsin 54143
Contact:
Site Public Contact
920-433-8889
Christy.Gilchrist@hshs.org

Aurora Cancer Care-Milwaukee
Milwaukee, Wisconsin 53209
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

Aurora Saint Luke's Medical Center
Milwaukee, Wisconsin 53215
Contact:
Site Public Contact
412-339-5294
Roster@nrgoncology.org

Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin 53226
Contact:
Site Public Contact
414-805-4380

Aurora Sinai Medical Center
Milwaukee, Wisconsin 53233
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

Saint Vincent Hospital Cancer Center at Oconto Falls
Oconto Falls, Wisconsin 54154
Contact:
Site Public Contact
920-433-8889
Christy.Gilchrist@hshs.org

Vince Lombardi Cancer Clinic - Oshkosh
Oshkosh, Wisconsin 54904
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

Aurora Cancer Care-Racine
Racine, Wisconsin 53406
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

Vince Lombardi Cancer Clinic-Sheboygan
Sheboygan, Wisconsin 53081
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

Saint Vincent Hospital Cancer Center at Sturgeon Bay
Sturgeon Bay, Wisconsin 54235-1495
Contact:
Site Public Contact
920-433-8889
Christy.Gilchrist@hshs.org

Aurora Medical Center in Summit
Summit, Wisconsin 53066
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

Vince Lombardi Cancer Clinic-Two Rivers
Two Rivers, Wisconsin 54241
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

Aurora Cancer Care-Milwaukee West
Wauwatosa, Wisconsin 53226
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

Aurora West Allis Medical Center
West Allis, Wisconsin 53227
Contact:
Site Public Contact
414-302-2304
ncorp@aurora.org

More Details

NCT ID
NCT02502266
Status
Recruiting
Sponsor
National Cancer Institute (NCI)

Detailed Description

PRIMARY OBJECTIVES:

I. 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:

I. 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 and Phase III) 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:

I. 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 III)

EXPLORATORY OBJECTIVES:

I. 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) and olaparib PO as determined from an ongoing Phase I study. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

ARM IV (OLAPARIB): Patients receive olaparib PO twice daily (BID) on days 1-28. Courses 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. Courses 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.