Testing the Combination of Olaparib and Durvalumab, Cediranib and Durvalumab, Olaparib and Capivasertib, and Cediranib Alone in Recurrent or Refractory Endometrial Cancer Following the Earlier Phase of the Study That Tested Olaparib and Cediranib in Comparison to Cediranib Alone, and Olaparib Alone
Endometrial Adenocarcinoma, Endometrial Mixed Cell Adenocarcinoma, Endometrial Serous Adenocarcinoma
About this trial
This is an interventional treatment trial for Endometrial Adenocarcinoma
Eligibility Criteria
Inclusion Criteria:
- Patients must have recurrent or persistent endometrial carcinoma, which is refractory to curative therapy or established treatments; histologic confirmation of the original primary tumor is required; patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.); NOTE: clear cell histology is excluded
Patients must have evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or non-measurable (detectable) disease
- Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be > 15 mm in short axis when measured by CT or MRI; patients with measurable disease must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST version 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
Non-measurable (detectable) disease in a patient is defined in this protocol as one who does not have measurable disease but has at least one of the following conditions:
- Ascites and/or pleural effusion attributed to tumor;
- Solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions
- Patients must have signed an approved informed consent and authorization permitting release of personal health information
- Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen
- Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease according to the following definition: cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa; Note: patients on this non-cytotoxic study are allowed to receive one additional cytotoxic chemotherapy regimen for management of recurrent or persistent disease, as defined above; however, patients are encouraged to enroll on second-line non-cytotoxic studies prior to receiving additional cytotoxic therapy
- Patients may have received non cytotoxic therapy including immunotherapy (1 prior line in either upfront or recurrent setting) but excluding cediranib, olaparib, AZD5363 (capivasertib), durvalumab (MEDI4736), or the combination of lenvatinib and pembrolizumab for the management of recurrent or persistent disease; prior hormonal therapy is allowed; hormonal therapy for grade 1 endometrial cancers with low volume or indolent disease is encouraged
- Bevacizumab, or one course of single-agent immune-checkpoint therapy, excluding durvalumab (MEDI4736), is permitted prior to enrollment on this trial
- Body weight > 30 kg
- Age >= 18
- The trial is open to females only (including women with an intact uterus with uterine cancer); fertile females of childbearing potential need to agree to use adequate contraceptive measures from 2 weeks prior to the study and until 1 month after study treatment discontinuation, and have a negative serum or urine pregnancy test within 3 days prior to the start of study treatment
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2 (Karnofsky >= 60%) within 7 days prior to registration; patients should have no deterioration over the previous two weeks
- Hemoglobin >= 10 mg/dL with no blood transfusion in the past 28 days (within 28 days prior to administration of study drug)
- Platelet count >= 100 x 10^9/L (within 28 days prior to administration of study drug)
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within 28 days prior to administration of study drug)
- Patients must have creatinine clearance estimated of >= 51 mL/min using the Cockcroft Gault equation or based on a 24-hour urine test (within 28 days prior to administration of study drug)
- Serum bilirubin =< 1.5 X upper limit of normal (ULN) (within 28 days prior to administration of study drug)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN (within 28 days prior to administration of study drug)
- Urine protein: creatinine (UPC) < 1 or < 2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart. Patients with 2+ proteinuria on dipstick must also have UPC < 0.5 on 2 consecutive samples (within 28 days prior to administration of study drug)
- Patients must be able to swallow and retain oral medications and without gastrointestinal illnesses that would preclude absorption of cediranib, olaparib, or AZD5363 (capivasertib)
Patients must have adequately controlled blood pressure (BP), with a BP no greater than 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility; 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; patients with hypertension may be managed with up to a maximum of three antihypertensive medications; it is strongly recommended that patients who are on three antihypertensive medications be followed by a cardiologist or blood pressure specialist for management of blood pressure while on protocol
- Note: Patients must be willing and able to check and record daily blood pressure readings
- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
- Adequately controlled thyroid function, with no symptoms of thyroid dysfunction
Postmenopausal or evidence of non-childbearing status for women of childbearing potential as confirmed by a negative urine or serum pregnancy test within 7 days prior to start of investigational products (IPs); postmenopausal is defined as:
- Age >= 60 years, or
Age < 60 with any one or more of the conditions below:
- Amenorrheic for >= 1 year in the absence of chemotherapy and/or hormonal treatments,
- Luteinizing hormone and/or follicle stimulating hormone and/or estradiol levels in the post-menopausal range
- Radiation-induced oophorectomy with last menses > 1 year ago,
- Chemotherapy-induced menopause with > 1 year interval since last menses,
- Surgical sterilization (bilateral oophorectomy or hysterectomy)
- Patients must have a life expectancy of greater than 16 weeks
- Patients with a previous diagnosis of immune or inflammatory colitis or chronic diarrhea > 1 month without immune or inflammatory colitis are eligible with adequately controlled colitis (no diarrhea greater than grade 1 for at least 28 days) and in the absence of symptoms related to colonic dysfunction; patients who required steroids for prior immune related colitis are not eligible
Females of child-bearing potential should use two forms of highly reliable methods of contraception from the time of screening until 4 weeks after discontinuing study treatment.
Acceptable methods of contraception include:
- Established use of oral, injected or implanted hormonal methods of contraception.
- Placement of an intrauterine device or intrauterine system.
- Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
- Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).
- True abstinence (i.e., not engaging in sexual activity for the total duration of study treatment and the treatment washout period is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control).
- Bilateral tubal occlusion or salpingectomy
Acceptable non-hormonal birth control methods include:
- Total/True abstinence: When the patient refrains from any form of sexual intercourse and this is in line with their usual and/or preferred lifestyle; this must continue for the total duration of the trial and for at least 1 month after the last dose of study drug <<for 3 months after last dose for male patients>>. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods, or declaration of abstinence solely for the duration of a trial) and withdrawal are not acceptable methods of contraception]
- Vasectomised sexual partner PLUS male condom. With participant assurance that partner received post-vasectomy confirmation of azoospermia.
- Tubal occlusion PLUS male condom
- Intrauterine device (IUD) PLUS male condom. Provided coils are copper-banded.
Acceptable hormonal methods:
- Normal and low dose combined oral pills PLUS male condom.
- Cerazette (desogestrel) PLUS male condom. Cerazette is currently the only highly efficacious progesterone-based pill.
- Hormonal shot or injection (e.g., Depo-Provera) PLUS male condom.
- Etonogestrel implants (e.g., Implanon, Norplant) PLUS male condom.
- Norelgestromin/EE transdermal system PLUS male condom
- Intrauterine system [IUS] device (e.g., levonorgestrel releasing IUS -Mirena) PLUS male condom.
- Intravaginal device (e.g., EE and etonogestrel) PLUS male condom
Exclusion Criteria:
- Prior enrollment into a clinical trial including cediranib or olaparib; Note: prior bevacizumab is not an exclusion criterion
- Prior enrollment into a clinical trial including cediranib, olaparib, AZD5363 (capivasertib), durvalumab (MEDI4736), or the combination of lenvatinib and pembrolizumab. Note: Prior bevacizumab or single-agent immune checkpoint blockade, excluding durvalumab (MEDI4736), is not an exclusion criterion
- Prior chemotherapy, endocrine therapy, radiotherapy, or investigational agents within 4 weeks
- More than one prior line of treatment with immune checkpoint blockade therapy
- Current signs/symptoms of bowel obstruction and/or signs/symptoms of bowel obstruction within the preceding 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
- Uncontrolled intercurrent illness including, but not limited to known ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or psychiatric illness/social situations that would limit compliance with study requirements
- Concomitant use of known strong cytochrome (CYP) 3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil); the required washout period prior to starting study treatments is 2 weeks for strong inhibitors, and at least 1 week for moderate inhibitors
- Concomitant use of potent inhibitors or inducers of CYP3A4 within 2 weeks before the start of study treatment (3 weeks for St John's wort), or sensitive substrates of CYP3A4, CYP2C9 and/or CYP2D6 with a narrow therapeutic window within 1 week before the start of study treatment. Concomitant use of drugs known to prolong the QT interval within 5 half-lives of the first dose of study treatment
- 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; for women of childbearing capacity a negative pregnancy test is required
- Known human immunodeficiency virus (HIV)-positive individuals are ineligible because of the potential for pharmacokinetic interactions between many anti-HIV drugs and cediranib, olaparib, and/or AZD5363 (capivasertib); in addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy
- Known active hepatitis B or hepatitis C infection on antiviral treatment
- Prior history of stroke or transient ischemic attack within the last 6 months
Left ventricular ejection fraction (LVEF) < lower limit of normal (LLN) per institutional guidelines, or < 55%, if threshold for normal not otherwise specified by institutional guidelines, for patients with the following risk factors:
- Prior treatment with anthracyclines
- Prior treatment with trastuzumab
- Prior central thoracic radiation therapy (RT), including exposure of heart to therapeutic doses of ionizing RT
- History of myocardial infarction within 6-12 months prior to start of IPs
- Prior history of other significant impaired cardiac function
Patients with any of the following:
- History of myocardial infarction within 6 months prior to starting treatment
- Unstable angina
- Resting electrocardiogram (ECG) with clinically significant abnormal findings or with corrected QT interval (QTc) > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
- New York Heart Association functional classification of III or IV
- Prior history of hypertensive crisis or hypertensive encephalopathy
- Major surgical procedure within 4 weeks prior to starting treatment; patients must have recovered from any effects of any major surgery and surgical wound should have healed prior to starting treatment
- History of intra-abdominal abscess within 3 months prior to starting treatment
- 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
- No prior allogeneic bone marrow transplant or double umbilical cord blood transplant
Sites / Locations
- University of Alabama at Birmingham Cancer Center
- Anchorage Associates in Radiation Medicine
- Anchorage Radiation Therapy Center
- Alaska Breast Care and Surgery LLC
- Alaska Oncology and Hematology LLC
- Alaska Women's Cancer Care
- Anchorage Oncology Centre
- Katmai Oncology Group
- Providence Alaska Medical Center
- Fairbanks Memorial Hospital
- CTCA at Western Regional Medical Center
- Kingman Regional Medical Center
- Cancer Center at Saint Joseph's
- Mayo Clinic Hospital in Arizona
- Mayo Clinic in Arizona
- University of Arizona Cancer Center-Orange Grove Campus
- Banner University Medical Center - Tucson
- University of Arizona Cancer Center-North Campus
- Mercy Hospital Fort Smith
- CHI Saint Vincent Cancer Center Hot Springs
- University of Arkansas for Medical Sciences
- Kaiser Permanente-Anaheim
- Mission Hope Medical Oncology - Arroyo Grande
- PCR Oncology
- Sutter Auburn Faith Hospital
- Sutter Cancer Centers Radiation Oncology Services-Auburn
- Kaiser Permanente-Baldwin Park
- Kaiser Permanente-Bellflower
- Alta Bates Summit Medical Center-Herrick Campus
- Tower Cancer Research Foundation
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- Mills-Peninsula Medical Center
- Sutter Cancer Centers Radiation Oncology Services-Cameron Park
- Mercy Cancer Center �� Carmichael
- Mercy San Juan Medical Center
- Eden Hospital Medical Center
- Sutter Davis Hospital
- Mercy Cancer Center - Elk Grove
- Kaiser Permanente-Fontana
- Palo Alto Medical Foundation-Fremont
- Kaiser Permanente - Harbor City
- Kaiser Permanente-Irvine
- Kaiser Permanente Los Angeles Medical Center
- Kaiser Permanente West Los Angeles
- Cedars Sinai Medical Center
- Memorial Medical Center
- Palo Alto Medical Foundation-Camino Division
- Palo Alto Medical Foundation-Gynecologic Oncology
- Providence Queen of The Valley
- Sutter Cancer Research Consortium
- Kaiser Permanente-Ontario
- Palo Alto Medical Foundation Health Care
- Kaiser Permanente - Panorama City
- Kaiser Permanente-Riverside
- Mercy Cancer Center - Rocklin
- Sutter Cancer Centers Radiation Oncology Services-Roseville
- Sutter Roseville Medical Center
- Mercy Cancer Center - Sacramento
- Sutter Medical Center Sacramento
- Kaiser Permanente-San Diego Mission
- Kaiser Permanente-San Diego Zion
- California Pacific Medical Center-Pacific Campus
- Pacific Central Coast Health Center-San Luis Obispo
- Kaiser Permanente-San Marcos
- Palo Alto Medical Foundation-Santa Cruz
- Mission Hope Medical Oncology - Santa Maria
- Providence Medical Foundation - Santa Rosa
- Sutter Pacific Medical Foundation
- Providence Santa Rosa Memorial Hospital
- Palo Alto Medical Foundation-Sunnyvale
- Torrance Memorial Physician Network - Cancer Care
- Sutter Cancer Centers Radiation Oncology Services-Vacaville
- Sutter Solano Medical Center/Cancer Center
- Kaiser Permanente-Woodland Hills
- Woodland Memorial Hospital
- Rocky Mountain Cancer Centers-Aurora
- The Medical Center of Aurora
- UCHealth University of Colorado Hospital
- Boulder Community Hospital
- Boulder Community Foothills Hospital
- Rocky Mountain Cancer Centers-Boulder
- Rocky Mountain Cancer Centers - Centennial
- Penrose-Saint Francis Healthcare
- Rocky Mountain Cancer Centers-Penrose
- UCHealth Memorial Hospital Central
- Memorial Hospital North
- Saint Francis Cancer Center
- Denver Health Medical Center
- National Jewish Health-Main Campus
- The Women's Imaging Center
- Porter Adventist Hospital
- Colorado Blood Cancer Institute
- Presbyterian - Saint Lukes Medical Center - Health One
- Rocky Mountain Cancer Centers-Midtown
- SCL Health Saint Joseph Hospital
- Rocky Mountain Cancer Centers-Rose
- Rose Medical Center
- Western Surgical Care
- Mercy Medical Center
- Southwest Oncology PC
- Mountain Blue Cancer Care Center - Swedish
- Rocky Mountain Cancer Centers - Swedish
- Swedish Medical Center
- The Melanoma and Skin Cancer Institute
- Poudre Valley Hospital
- Cancer Care and Hematology-Fort Collins
- Mountain Blue Cancer Care Center
- National Jewish Health-Western Hematology Oncology
- Saint Mary's Hospital and Regional Medical Center
- North Colorado Medical Center
- UCHealth Greeley Hospital
- Good Samaritan Medical Center
- Rocky Mountain Cancer Centers-Lakewood
- Saint Anthony Hospital
- Rocky Mountain Cancer Centers-Littleton
- Littleton Adventist Hospital
- Rocky Mountain Cancer Centers-Sky Ridge
- Sky Ridge Medical Center
- Longmont United Hospital
- Rocky Mountain Cancer Centers-Longmont
- Medical Center of the Rockies
- McKee Medical Center
- Parker Adventist Hospital
- Rocky Mountain Cancer Centers-Parker
- Saint Mary Corwin Medical Center
- Rocky Mountain Cancer Centers - Pueblo
- National Jewish Health-Northern Hematology Oncology
- Rocky Mountain Cancer Centers-Thornton
- SCL Health Lutheran Medical Center
- Smilow Cancer Hospital-Derby Care Center
- Smilow Cancer Hospital Care Center-Fairfield
- Smilow Cancer Hospital Care Center - Guilford
- Hartford Hospital
- Smilow Cancer Hospital Care Center at Saint Francis
- The Hospital of Central Connecticut
- Smilow Cancer Center/Yale-New Haven Hospital
- Yale University
- Yale-New Haven Hospital North Haven Medical Center
- Smilow Cancer Hospital-Torrington Care Center
- Smilow Cancer Hospital Care Center-Trumbull
- Smilow Cancer Hospital-Waterbury Care Center
- Smilow Cancer Hospital Care Center - Waterford
- Beebe South Coastal Health Campus
- Beebe Medical Center
- Delaware Clinical and Laboratory Physicians PA
- Helen F Graham Cancer Center
- Medical Oncology Hematology Consultants PA
- Christiana Care Health System-Christiana Hospital
- Beebe Health Campus
- TidalHealth Nanticoke / Allen Cancer Center
- Christiana Care Health System-Wilmington Hospital
- Sibley Memorial Hospital
- George Washington University Medical Center
- Florida Cancer Specialists - Bradenton Cancer Center
- University of Florida Health Science Center - Gainesville
- Jupiter Medical Center
- Sacred Heart Hospital
- Florida Cancer Specialists - Sarasota
- Florida Cancer Specialists - Sarasota Downtown
- Sarasota Memorial Hospital
- Florida Cancer Specialists - Venice Island
- Florida Cancer Specialists - Venice Healthpark
- Grady Health System
- Emory University Hospital Midtown
- Piedmont Hospital
- Emory University Hospital/Winship Cancer Institute
- Emory Saint Joseph's Hospital
- Piedmont Fayette Hospital
- CTCA at Southeastern Regional Medical Center
- Memorial Health University Medical Center
- Summit Cancer Care-Memorial
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Summit Cancer Care-Candler
- Hawaii Cancer Care - Westridge
- Pali Momi Medical Center
- Queen's Cancer Center - Pearlridge
- The Cancer Center of Hawaii-Pali Momi
- Hawaii Cancer Care Inc - Waterfront Plaza
- Island Urology
- Queen's Cancer Cenrer - POB I
- Queen's Medical Center
- Straub Clinic and Hospital
- University of Hawaii Cancer Center
- Hawaii Cancer Care Inc-Liliha
- Kuakini Medical Center
- Queen's Cancer Center - Kuakini
- The Cancer Center of Hawaii-Liliha
- Kapiolani Medical Center for Women and Children
- Wilcox Memorial Hospital and Kauai Medical Clinic
- Saint Alphonsus Cancer Care Center-Boise
- Saint Luke's Cancer Institute - Boise
- Saint Alphonsus Cancer Care Center-Caldwell
- Kootenai Health - Coeur d'Alene
- Walter Knox Memorial Hospital
- Saint Luke's Cancer Institute - Fruitland
- Idaho Urologic Institute-Meridian
- Saint Luke's Cancer Institute - Meridian
- Saint Luke's Cancer Institute - Nampa
- Saint Alphonsus Cancer Care Center-Nampa
- Kootenai Clinic Cancer Services - Post Falls
- Kootenai Cancer Clinic
- Saint Luke's Cancer Institute - Twin Falls
- Saint Anthony's Health
- Rush - Copley Medical Center
- Advocate Good Shepherd Hospital
- Bromenn Lifecare Center
- Illinois CancerCare-Bloomington
- Illinois CancerCare-Canton
- Memorial Hospital of Carbondale
- SIH Cancer Institute
- Illinois CancerCare-Carthage
- Centralia Oncology Clinic
- Saint Mary's Hospital
- Northwestern University
- John H Stroger Jr Hospital of Cook County
- Rush University Medical Center
- University of Chicago Comprehensive Cancer Center
- Advocate Illinois Masonic Medical Center
- AMG Crystal Lake - Oncology
- Carle at The Riverfront
- Cancer Care Specialists of Illinois - Decatur
- Decatur Memorial Hospital
- Illinois CancerCare-Dixon
- Advocate Good Samaritan Hospital
- Carle Physician Group-Effingham
- Crossroads Cancer Center
- Advocate Sherman Hospital
- Illinois CancerCare-Eureka
- NorthShore University HealthSystem-Evanston Hospital
- Illinois CancerCare-Galesburg
- Western Illinois Cancer Treatment Center
- Northwestern Medicine Cancer Center Delnor
- NorthShore University HealthSystem-Glenbrook Hospital
- Ingalls Memorial Hospital
- Advocate South Suburban Hospital
- NorthShore University HealthSystem-Highland Park Hospital
- Sudarshan K Sharma MD Limited-Gynecologic Oncology
- Illinois CancerCare-Kewanee Clinic
- Northwestern Medicine Lake Forest Hospital
- Illinois CancerCare-Macomb
- Carle Physician Group-Mattoon/Charleston
- Good Samaritan Regional Health Center
- UC Comprehensive Cancer Center at Silver Cross
- Bromenn Regional Medical Center
- Carle Cancer Institute Normal
- Cancer Care Center of O'Fallon
- Advocate Christ Medical Center
- University of Chicago Medicine-Orland Park
- Illinois CancerCare-Ottawa Clinic
- Advocate Lutheran General Hospital
- Illinois CancerCare-Pekin
- Illinois CancerCare-Peoria
- Methodist Medical Center of Illinois
- Illinois CancerCare-Peru
- Valley Radiation Oncology
- Illinois CancerCare-Princeton
- Southern Illinois University School of Medicine
- Springfield Clinic
- Memorial Medical Center
- Southwest Illinois Health Services LLP
- Carle Cancer Center
- The Carle Foundation Hospital
- Northwestern Medicine Cancer Center Warrenville
- Illinois CancerCare - Washington
- Rush-Copley Healthcare Center
- Midwestern Regional Medical Center
- Northwest Cancer Center - Main Campus
- Northwest Oncology LLC
- Parkview Hospital Randallia
- Parkview Regional Medical Center
- Northwest Cancer Center - Hobart
- Saint Mary Medical Center
- Indiana University/Melvin and Bren Simon Cancer Center
- Sidney and Lois Eskenazi Hospital
- Ascension Saint Vincent Indianapolis Hospital
- Saint Catherine Hospital
- The Community Hospital
- Women's Diagnostic Center - Munster
- Reid Health
- Memorial Hospital of South Bend
- Northwest Cancer Center - Valparaiso
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Alegent Health Mercy Hospital
- Greater Regional Medical Center
- Iowa Methodist Medical Center
- Medical Oncology and Hematology Associates-Des Moines
- Broadlawns Medical Center
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- Iowa Lutheran Hospital
- Trinity Regional Medical Center
- University of Iowa/Holden Comprehensive Cancer Center
- Methodist West Hospital
- Mercy Medical Center-West Lakes
- Central Care Cancer Center - Garden City
- Central Care Cancer Center - Great Bend
- Associates In Womens Health
- Cancer Center of Kansas-Wichita Medical Arts Tower
- Ascension Via Christi Hospitals Wichita
- Cancer Center of Kansas - Wichita
- Flaget Memorial Hospital
- Baptist Health Corbin
- Commonwealth Cancer Center-Corbin
- Saint Elizabeth Healthcare Edgewood
- Baptist Health Lexington
- Saint Joseph Hospital
- Saint Joseph Radiation Oncology Resource Center
- Saint Joseph Hospital East
- Saint Joseph London
- Jewish Hospital
- Baptist Health Louisville
- Saints Mary and Elizabeth Hospital
- UofL Health Medical Center Northeast
- Baptist Health Madisonville/Merle Mahr Cancer Center
- Saint Joseph Mount Sterling
- Baptist Health Paducah
- Mercy Health - Paducah Medical Oncology and Hematology
- Baptist Health Richmond
- Jewish Hospital Medical Center South
- Mary Bird Perkins Cancer Center
- Women's Cancer Care-Covington
- Ochsner Baptist Medical Center
- Ochsner Medical Center Jefferson
- Eastern Maine Medical Center
- Lafayette Family Cancer Center-EMMC
- Maine Medical Center- Scarborough Campus
- Anne Arundel Medical Center
- Greater Baltimore Medical Center
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Walter Reed National Military Medical Center
- University of Maryland Shore Medical Center at Easton
- Christiana Care - Union Hospital
- Beverly Hospital
- Lahey Hospital and Medical Center
- Addison Gilbert Hospital
- Lahey Medical Center-Peabody
- Baystate Medical Center
- Winchester Hospital
- UMass Memorial Medical Center - Memorial Division
- University of Michigan Comprehensive Cancer Center
- University of Michigan - Brighton Center for Specialty Care
- Wayne State University/Karmanos Cancer Institute
- Weisberg Cancer Treatment Center
- Huron Medical Center PC
- Lake Huron Medical Center
- Riverwood Healthcare Center
- Essentia Health - Baxter Clinic
- Sanford Joe Lueken Cancer Center
- Essentia Health Saint Joseph's Medical Center
- Fairview Ridges Hospital
- Minnesota Oncology - Burnsville
- Cambridge Medical Center
- Mercy Hospital
- Essentia Health - Deer River Clinic
- Essentia Health Saint Mary's - Detroit Lakes Clinic
- Essentia Health Cancer Center
- Essentia Health Saint Mary's Medical Center
- Miller-Dwan Hospital
- Fairview Southdale Hospital
- Essentia Health - Ely Clinic
- Lake Region Healthcare Corporation-Cancer Care
- Essentia Health - Fosston
- Unity Hospital
- Essentia Health Hibbing Clinic
- Essentia Health - International Falls Clinic
- Fairview Clinics and Surgery Center Maple Grove
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Hennepin County Medical Center
- Health Partners Inc
- Monticello Cancer Center
- Essentia Health - Moose Lake Clinic
- New Ulm Medical Center
- Essentia Health - Park Rapids
- Fairview Northland Medical Center
- North Memorial Medical Health Center
- Mayo Clinic in Rochester
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Essentia Health Sandstone
- Saint Francis Regional Medical Center
- Lakeview Hospital
- Sanford Thief River Falls Medical Center
- Essentia Health Virginia Clinic
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Sanford Cancer Center Worthington
- Fairview Lakes Medical Center
- University of Mississippi Medical Center
- Saint Louis Cancer and Breast Institute-Ballwin
- Central Care Cancer Center - Bolivar
- Parkland Health Center-Bonne Terre
- Cox Cancer Center Branson
- Saint Francis Medical Center
- Southeast Cancer Center
- MU Health - University Hospital/Ellis Fischel Cancer Center
- Parkland Health Center - Farmington
- Capital Region Southwest Campus
- Freeman Health System
- Mercy Hospital Joplin
- Delbert Day Cancer Institute at PCRMC
- Mercy Clinic-Rolla-Cancer and Hematology
- Heartland Regional Medical Center
- Saint Louis Cancer and Breast Institute-South City
- Washington University School of Medicine
- Mercy Hospital South
- Missouri Baptist Medical Center
- Mercy Hospital Saint Louis
- Sainte Genevieve County Memorial Hospital
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Missouri Baptist Sullivan Hospital
- Missouri Baptist Outpatient Center-Sunset Hills
- Mercy Hospital Washington
- Community Hospital of Anaconda
- Billings Clinic Cancer Center
- Saint Vincent Healthcare
- Saint Vincent Frontier Cancer Center
- Bozeman Deaconess Hospital
- Saint James Community Hospital and Cancer Treatment Center
- Benefis Healthcare- Sletten Cancer Institute
- Great Falls Clinic
- Saint Peter's Community Hospital
- Kalispell Regional Medical Center
- Saint Patrick Hospital - Community Hospital
- Community Medical Hospital
- CHI Health Saint Francis
- Heartland Hematology and Oncology
- CHI Health Good Samaritan
- Saint Elizabeth Regional Medical Center
- Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
- Nebraska Methodist Hospital
- Oncology Associates PC
- Nebraska Medicine-Village Pointe
- Alegent Health Immanuel Medical Center
- Hematology and Oncology Consultants PC
- Alegent Health Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- Creighton University Medical Center
- University of Nebraska Medical Center
- Midlands Community Hospital
- Carson Tahoe Regional Medical Center
- Cancer and Blood Specialists-Henderson
- Comprehensive Cancer Centers of Nevada - Henderson
- Comprehensive Cancer Centers of Nevada-Horizon Ridge
- Las Vegas Cancer Center-Henderson
- OptumCare Cancer Care at Seven Hills
- Comprehensive Cancer Centers of Nevada-Southeast Henderson
- GenesisCare USA - Henderson
- Las Vegas Urology - Green Valley
- Las Vegas Urology - Pebble
- Urology Specialists of Nevada - Green Valley
- Las Vegas Urology - Pecos
- Desert West Surgery
- OptumCare Cancer Care at Charleston
- University Medical Center of Southern Nevada
- Hope Cancer Care of Nevada
- Cancer and Blood Specialists-Shadow
- Radiation Oncology Centers of Nevada Central
- Urology Specialists of Nevada - Central
- Women's Cancer Center of Nevada
- GenesisCare USA - Las Vegas
- HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
- Sunrise Hospital and Medical Center
- HealthCare Partners Medical Group Oncology/Hematology-San Martin
- Las Vegas Prostate Cancer Center
- Las Vegas Urology - Sunset
- Urology Specialists of Nevada - Southwest
- Radiation Oncology Centers of Nevada Southeast
- Ann M Wierman MD LTD
- Cancer and Blood Specialists-Tenaya
- Comprehensive Cancer Centers of Nevada - Northwest
- GenesisCare USA - Vegas Tenaya
- HealthCare Partners Medical Group Oncology/Hematology-Tenaya
- Las Vegas Urology - Cathedral Rock
- Las Vegas Urology - Smoke Ranch
- OptumCare Cancer Care at MountainView
- Urology Specialists of Nevada - Northwest
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
- Comprehensive Cancer Centers of Nevada - Town Center
- Comprehensive Cancer Centers of Nevada-Summerlin
- Summerlin Hospital Medical Center
- Las Vegas Cancer Center-Medical Center
- Comprehensive Cancer Centers of Nevada
- GenesisCare USA - Fort Apache
- OptumCare Cancer Care at Fort Apache
- HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
- Comprehensive Cancer Centers of Nevada - Central Valley
- University Cancer Center
- Hope Cancer Care of Nevada-Pahrump
- Renown Regional Medical Center
- Saint Mary's Regional Medical Center
- Radiation Oncology Associates
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Norris Cotton Cancer Center-Manchester
- Dartmouth Cancer Center - Nashua
- Virtua Memorial
- Virtua Voorhees
- University of New Mexico Cancer Center
- Southwest Gynecologic Oncology Associates Inc
- Presbyterian Rust Medical Center/Jorgensen Cancer Center
- Women's Cancer Care Associates LLC
- Montefiore Medical Center-Einstein Campus
- Montefiore Medical Center-Weiler Hospital
- Montefiore Medical Center - Moses Campus
- Roswell Park Cancer Institute
- Mount Sinai Chelsea
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- Mount Sinai Hospital
- University of Rochester
- Dickstein Cancer Treatment Center
- Randolph Hospital
- Hope Women's Cancer Centers-Asheville
- Cone Health Cancer Center at Alamance Regional
- Duke Cancer Institute Cary
- UNC Lineberger Comprehensive Cancer Center
- Novant Health Presbyterian Medical Center
- Novant Health Carolina Surgical - Randolph
- Oncology Specialists of Charlotte
- Southern Oncology Specialists-Charlotte
- Southeastern Medical Oncology Center-Clinton
- Duke University Medical Center
- Southeastern Medical Oncology Center-Goldsboro
- Wayne Memorial Hospital
- Cone Health Cancer Center
- Novant Health Cancer Institute - Huntersville
- Novant Health Presbyterian Medical Center Huntersville
- Southern Oncology Specialists-Huntersville
- Onslow Memorial Hospital
- Southeastern Medical Oncology Center-Jacksonville
- Novant Health Cancer Institute - Kernersville
- Matthews Radiation Oncology Center
- Novant Health Cancer Institute - Matthews
- Cone Heath Cancer Center at Mebane
- Lake Norman Radiation Oncology Center-Mooresville
- Novant Health Cancer Institute - Mooresville
- Novant Health Cancer Institute - Mount Airy
- Duke Women's Cancer Care Raleigh
- Duke Raleigh Hospital
- Annie Penn Memorial Hospital
- Novant Health Cancer Institute - Rowan
- Rowan Regional Medical Center
- Novant Health Cancer Institute - Statesville
- Novant Health Cancer Institute - Thomasville
- Novant Health Cancer Institute - Wilkesboro
- Novant Health Forsyth Medical Center
- Novant Health Oncology Specialists
- Sanford Bismarck Medical Center
- Essentia Health Cancer Center-South University Clinic
- Sanford South University Medical Center
- Sanford Medical Center Fargo
- Sanford Broadway Medical Center
- Sanford Roger Maris Cancer Center
- Essentia Health - Jamestown Clinic
- Summa Health System - Akron Campus
- Aultman Alliance Community Hospital
- UHHS-Chagrin Highlands Medical Center
- Indu and Raj Soin Medical Center
- Strecker Cancer Center-Belpre
- Saint Elizabeth Boardman Hospital
- Aultman Health Foundation
- Dayton Physicians LLC-Miami Valley South
- Miami Valley Hospital South
- Geauga Hospital
- Adena Regional Medical Center
- Good Samaritan Hospital - Cincinnati
- Oncology Hematology Care Inc-Kenwood
- Bethesda North Hospital
- TriHealth Cancer Institute-Westside
- TriHealth Cancer Institute-Anderson
- Case Western Reserve University
- MetroHealth Medical Center
- Cleveland Clinic Cancer Center/Fairview Hospital
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- Mount Carmel East Hospital
- Columbus Oncology and Hematology Associates Inc
- Riverside Methodist Hospital
- Grant Medical Center
- The Mark H Zangmeister Center
- Mount Carmel Health Center West
- Doctors Hospital
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Dayton Physician LLC-Miami Valley Hospital North
- Miami Valley Hospital North
- Delaware Health Center-Grady Cancer Center
- Delaware Radiation Oncology
- Grady Memorial Hospital
- Columbus Oncology and Hematology Associates
- Mercy Cancer Center-Elyria
- Armes Family Cancer Center
- Blanchard Valley Hospital
- Orion Cancer Care
- Atrium Medical Center-Middletown Regional Hospital
- Dayton Physicians LLC-Atrium
- Central Ohio Breast and Endocrine Surgery
- Dayton Physicians LLC-Wayne
- Wayne Hospital
- Mount Carmel Grove City Hospital
- Zangmeister Center Grove City
- Greater Dayton Cancer Center
- First Dayton Cancer Care
- Kettering Medical Center
- Fairfield Medical Center
- Saint Rita's Medical Center
- OhioHealth Mansfield Hospital
- Marietta Memorial Hospital
- OhioHealth Marion General Hospital
- Hillcrest Hospital Cancer Center
- UH Seidman Cancer Center at Lake Health Mentor Campus
- UH Seidman Cancer Center at Southwest General Hospital
- Knox Community Hospital
- Mount Carmel New Albany Surgical Hospital
- Licking Memorial Hospital
- Newark Radiation Oncology
- Mercy Health Perrysburg Cancer Center
- Southern Ohio Medical Center
- UH Seidman Cancer Center at Firelands Regional Medical Center
- Springfield Regional Cancer Center
- Springfield Regional Medical Center
- ProMedica Flower Hospital
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- Saint Vincent Mercy Medical Center
- Mercy Health - Saint Anne Hospital
- Dayton Physicians LLC - Troy
- Upper Valley Medical Center
- University Hospitals Sharon Health Center
- Saint Joseph Warren Hospital
- Saint Ann's Hospital
- UH Seidman Cancer Center at Saint John Medical Center
- UHHS-Westlake Medical Center
- Saint Elizabeth Youngstown Hospital
- Genesis Healthcare System Cancer Care Center
- University of Oklahoma Health Sciences Center
- Mercy Hospital Oklahoma City
- Oklahoma Cancer Specialists and Research Institute-Tulsa
- Saint Alphonsus Medical Center-Baker City
- Saint Charles Health System
- Clackamas Radiation Oncology Center
- Providence Cancer Institute Clackamas Clinic
- Bay Area Hospital
- Providence Newberg Medical Center
- Saint Alphonsus Medical Center-Ontario
- Providence Willamette Falls Medical Center
- Legacy Good Samaritan Hospital and Medical Center
- Providence Portland Medical Center
- Providence Saint Vincent Medical Center
- Saint Charles Health System-Redmond
- Legacy Meridian Park Hospital
- Jefferson Abington Hospital
- Bryn Mawr Hospital
- Christiana Care Health System-Concord Health Center
- Main Line Health Center-Collegeville
- Main Line Health Center-Exton
- Jefferson Hospital
- Riddle Memorial Hospital
- Forbes Hospital
- Paoli Memorial Hospital
- Thomas Jefferson University Hospital
- Allegheny General Hospital
- West Penn Hospital
- Chester County Hospital
- Reading Hospital
- Wexford Health and Wellness Pavilion
- Asplundh Cancer Pavilion
- Lankenau Medical Center
- Women and Infants Hospital
- AnMed Health Cancer Center
- Medical University of South Carolina
- Gibbs Cancer Center-Gaffney
- Saint Francis Hospital
- Saint Francis Cancer Center
- Gibbs Cancer Center-Pelham
- Spartanburg Medical Center
- MGC Hematology Oncology-Union
- Sanford Cancer Center Oncology Clinic
- Avera Cancer Institute
- Sanford USD Medical Center - Sioux Falls
- Memorial Hospital
- Pulmonary Medicine Center of Chattanooga-Hixson
- Memorial GYN Plus
- Dell Seton Medical Center at The University of Texas
- Saint Joseph Regional Cancer Center
- Parkland Memorial Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- Lyndon Baines Johnson General Hospital
- Houston Methodist Hospital
- M D Anderson Cancer Center
- Methodist Willowbrook Hospital
- Houston Methodist Sugar Land Hospital
- Providence Regional Cancer System-Aberdeen
- Overlake Medical Center
- PeaceHealth Saint Joseph Medical Center
- Harrison HealthPartners Hematology and Oncology-Bremerton
- Harrison Medical Center
- Highline Medical Center-Main Campus
- Providence Regional Cancer System-Centralia
- Swedish Cancer Institute-Edmonds
- Saint Elizabeth Hospital
- Providence Regional Cancer Partnership
- Saint Francis Hospital
- Swedish Cancer Institute-Issaquah
- Kadlec Clinic Hematology and Oncology
- Providence Regional Cancer System-Lacey
- Saint Clare Hospital
- PeaceHealth Saint John Medical Center
- Jefferson Healthcare
- Harrison HealthPartners Hematology and Oncology-Poulsbo
- Valley Medical Center
- Pacific Gynecology Specialists
- Swedish Medical Center-Ballard Campus
- FHCC South Lake Union
- Kaiser Permanente Washington
- Swedish Medical Center-Cherry Hill
- Swedish Medical Center-First Hill
- University of Washington Medical Center - Montlake
- PeaceHealth United General Medical Center
- Providence Regional Cancer System-Shelton
- Franciscan Research Center-Northwest Medical Plaza
- Northwest Medical Specialties PLLC
- PeaceHealth Southwest Medical Center
- Legacy Salmon Creek Hospital
- Providence Saint Mary Regional Cancer Center
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
- Providence Regional Cancer System-Yelm
- West Virginia University Charleston Division
- Duluth Clinic Ashland
- Northwest Wisconsin Cancer Center
- Aurora Cancer Care-Southern Lakes VLCC
- Marshfield Clinic-Chippewa Center
- Marshfield Medical Center-EC Cancer Center
- Mayo Clinic Health System-Eau Claire Clinic
- Aurora Health Center-Fond du Lac
- Aurora Health Care Germantown Health Center
- Aurora Cancer Care-Grafton
- Aurora BayCare Medical Center
- Essentia Health-Hayward Clinic
- Aurora Cancer Care-Kenosha South
- Gundersen Lutheran Medical Center
- Marshfield Clinic - Ladysmith Center
- Aurora Bay Area Medical Group-Marinette
- Marshfield Medical Center-Marshfield
- Aurora Cancer Care-Milwaukee
- Aurora Saint Luke's Medical Center
- Aurora Sinai Medical Center
- Marshfield Clinic-Minocqua Center
- Cancer Center of Western Wisconsin
- Vince Lombardi Cancer Clinic - Oshkosh
- Aurora Cancer Care-Racine
- Marshfield Medical Center-Rice Lake
- Vince Lombardi Cancer Clinic-Sheboygan
- Essentia Health-Spooner Clinic
- Marshfield Medical Center-River Region at Stevens Point
- Aurora Medical Center in Summit
- Essentia Health Saint Mary's Hospital - Superior
- Vince Lombardi Cancer Clinic-Two Rivers
- Marshfield Clinic-Wausau Center
- Aurora Cancer Care-Milwaukee West
- Aurora West Allis Medical Center
- Marshfield Medical Center - Weston
- Marshfield Clinic - Wisconsin Rapids Center
- Cheyenne Regional Medical Center-West
- Billings Clinic-Cody
- Welch Cancer Center
- Odette Cancer Centre- Sunnybrook Health Sciences Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm I (cediranib maleate)
Arm II (olaparib)
Arm III (cediranib maleate, olaparib)
Arm IV (olaparib, capivasertib)
Arm V (olaparib, durvalumab)
Arm VI (cediranib maleate, durvalumab)
Patients receive cediranib maleate PO QD. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. Additionally, patients undergo blood sample collection, bone marrow aspiration and biopsy, CT, Echo or MUGA on study.
Patients receive olaparib PO BID. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. Additionally, patients undergo blood sample collection, bone marrow aspiration and biopsy, CT, Echo or MUGA on study.
Patients receive olaparib PO BID and cediranib maleate PO QD. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. Additionally, patients undergo blood sample collection, bone marrow aspiration and biopsy, CT, Echo or MUGA on study.
Patients receive olaparib PO BID on days 1-28 and capivasertib PO BID on days 1-4 each week. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. Additionally, patients undergo blood sample collection, bone marrow aspiration and biopsy, CT, Echo or MUGA on study.
Patients receive olaparib PO BID on days 1-28 and durvalumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. Additionally, patients undergo blood sample collection, bone marrow aspiration and biopsy, CT, Echo or MUGA on study.
Patients receive cediranib maleate PO BID on days 1-28 and durvalumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. Additionally, patients undergo blood sample collection, bone marrow aspiration and biopsy, CT, Echo or MUGA on study.