Testing the Combination of the Study Drugs Cediranib and Olaparib in Recurrent Ovarian Cancer

NCT02345265 | Active Not Recruiting Phase 2 Results FDA Drug

• 13 other identifiers: NCI-2015-0005116-7009825UM1CA186644UM1CA186686UM1CA186690UM1CA186691UM1CA186704UM1CA186709UM1CA186712UM1CA186716UM1CA186717ZIABC011078
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 20

Brief Summary

This phase II trial studies how well olaparib and cediranib maleate work in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of improvement (recurrent). Olaparib and cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Fallopian Tube Carcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Ovarian Carcinoma; Ovarian High Grade Endometrioid Adenocarcinoma; Ovarian High Grade Serous Adenocarcinoma; Primary Peritoneal Carcinoma; Primary Peritoneal Endometrioid Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival (PFS) by HRR Status in Platinum-Sensitive Ovarian Cancer

  PFS determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), where disease progression represents at least a 20% increase in the sum of diameters of target lesions, appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. Homologous recombination repair (HRR) status was measured by the BROCA-HR assay. BROCA-HR is a targeted NGS platform including all known gynecologic cancer susceptibility genes and other DNA repair or related genes as well as a 3100 single nucleotide polymorphism panel to increase coverage for loss of heterozygosity (LOH) analysis. HRR status was associated as a pooled group against PFS using the Kaplan-Meier product-limit estimator with 95% confidence bands derived using Greenwood's formula.

  Interval from start of treatment to documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurs first, assessed up to 32 months.

• Objective Response Rate (ORR) in Platinum-Resistant Ovarian Cancer

  Responses determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI, where Objective Response (OR) represents either a Complete Response (CR; disappearance of all target lesions) or a Partial Response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum diameters); Objective Response (OR) = CR + PR.

  Up to 32 months

Secondary Outcomes (5)

• Biomarker Signature Development

  Up to 30 days post-treatment

• Overall Survival

  Up to 1 year

• Genetic Alterations

  Baseline

• Change in Circulating Endothelial Cells/Circulating Endothelial Precursor Cells

  Baseline to day 3

• Prevalence of Genetic Alteration Using Whole Exome Sequencing

  Baseline

Study Arms (1)

Treatment (olaparib and cediranib maleate)

EXPERIMENTAL

Patients receive olaparib PO BID and cediranib maleate PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a biopsy of tumor, blood sample collection, MUGA or echocardiogram, and CT scan or MRI scan throughout the study.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Cediranib Maleate; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Drug: Olaparib; Other: Questionnaire Administration

Interventions

Biopsy Procedure PROCEDURE

Undergo biopsy of tumor

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (olaparib and cediranib maleate)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (olaparib and cediranib maleate)

Cediranib Maleate DRUG

Given PO

Also known as: AZD2171, AZD2171 Maleate, Recentin

Treatment (olaparib and cediranib maleate)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (olaparib and cediranib maleate)

Echocardiography Test PROCEDURE

Undergo echocardiogram

Also known as: EC, Echocardiography

Treatment (olaparib and cediranib maleate)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI scan

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (olaparib and cediranib maleate)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (olaparib and cediranib maleate)

Olaparib DRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU 0059436, KU-0059436, KU0059436, Lynparza, Olanib, Olaparix, PARP Inhibitor AZD2281

Treatment (olaparib and cediranib maleate)

Questionnaire Administration OTHER

Ancillary studies

Treatment (olaparib and cediranib maleate)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed ovarian cancer, peritoneal cancer or fallopian tube cancer and must have a histological diagnosis of either high grade serous or high grade endometrioid cancer based on local histopathological findings; participants with a deleterious BRCA-mutation on a commercial Clinical Laboratory Improvement Amendments (CLIA) assay with other high-grade histologies are also eligible
• Due to the long acceptance of BRCA testing through Myriad, Myriad testing will be accepted as documentation of a deleterious mutation; 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 show a recognized germline deleterious BRCA1 or BRCA2 mutation or BRCA rearrangements is required to document the presence of a deleterious mutation
• Participants must have measurable disease via Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral CT scan, MRI, or calipers by clinical exam
• Patients may not have received prior poly ADP ribose polymerase (PARP) inhibitors
• Patients may have received but may not have progressed on prior anti-angiogenic therapy in the upfront setting
• For platinum sensitive cohort
• Cancer that has not progressed within 6 months of the last receipt of platinum-based chemotherapy
• No limit on the number of platinum-based lines
• No more than one prior non-platinum based line of therapy in the recurrent setting
• For platinum-resistant or -refractory cohort
• Disease that has progressed within 6 months of the last receipt of platinum-based chemotherapy
• No more than 1 prior line of therapy in the platinum-resistant/-refractory setting
• No limit on number of prior lines received in the platinum-sensitive setting prior to development of platinum-resistance (defined as disease progression within 6 months of platinum-based chemotherapy)
• Hormonal therapies used as single agents (i.e. tamoxifen, aromatase inhibitors) will not count towards line limit considerations
• Age \>= 18 years of age. Because no dosing or adverse event data are currently available on the use of cediranib or olaparib in patients under the age of 18, children are excluded from this study

You may not qualify if:

• Participants may not have had chemotherapy or radiation therapy (RT) within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study and must have recovered to =\< grade 1 from adverse events due to agents administered more than 3 weeks earlier; patients should not have received hormonal therapy for treatment of their cancer within 2 weeks of study entry
• Participants should not have received any other investigational agents nor have participated in an investigational trial within the past 4 weeks
• Participants may not have had prior use of PARP inhibitors; patients may not have received prior treatment affecting the VEGF pathway in the recurrent setting, including but not limited to thalidomide, bevacizumab, sunitinib, or sorafenib
• Participants may not have any evidence of ongoing inadequately controlled hypertension (defined as a systolic blood pressure \[BP\] of \> 140 mmHg or a diastolic BP of \> 90 mmHg); patients with hypertension may not be on more than three antihypertensive medications for management of their blood pressure (medications that combine two anti-hypertensives into one are considered as two medications); it is strongly recommended that patients who require three antihypertensive medications for baseline management of pre-existing hypertension be actively followed by a cardiologist or blood pressure specialist for management of BP while on protocol
• Participants may not have had any prior history of hypertensive crisis or hypertensive encephalopathy
• Participants may not have had history of abdominal fistula or gastrointestinal perforation; patients with a history of abdominal fistula will be considered eligible if the fistula has healed or was surgically repaired, there has been no evidence of fistula for at least 6 months, and patient is deemed to be at low risk of recurrent fistula
• Participants may not have had a history of intra-abdominal abscess within the past 3 months
• Participants may not have current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowel obstruction within 3 months prior to starting study drugs
• Participants may not have a dependency on intravenous (IV) hydration or total parenteral nutrition (TPN)
• Participants with any concomitant or prior invasive malignancies are ineligible with the following 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, clear cell, or other International Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions
• Prior cancer treated with curative intent with no evidence of recurrent disease 3 years following diagnosis and judged by the investigator to be at low risk of recurrence
• Participants with any of the following:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (20)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Keck Medical Center of USC Pasadena

Pasadena, California, 91105, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

NCI - Center for Cancer Research

Bethesda, Maryland, 20892, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08903, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

Biopsy; Specimen Handling; cediranib; Magnetic Resonance Spectroscopy; olaparib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Results Point of Contact

• Title: Dr. Joyce Liu
• Organization: Dana-Farber Cancer Institute

Joyce_Liu@dfci.harvard.edu

617-632-5269

Study Officials

• Joyce F Liu

  Dana-Farber - Harvard Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2015
• First Posted: January 26, 2015
• Study Start: May 23, 2016
• Primary Completion: July 7, 2022
• Study Completion (Estimated): March 4, 2027
• Last Updated: April 30, 2026
• Results First Posted: March 28, 2023

Record last verified: 2026-03

Locations

US (20)