Testing the Addition of an Immunotherapy Drug, Tremelimumab, to the PARP Inhibition Drug, Olaparib, for Recurrent Ovarian, Fallopian Tube or Peritoneal Cancer
A Phase II Randomized Trial of Olaparib Versus Olaparib Plus Tremelimumab in Platinum-Sensitive Recurrent Ovarian Cancer
3 other identifiers
interventional
61
1 country
20
Brief Summary
This phase II trial studies how well olaparib with or without tremelimumab works in treating patients with ovarian, fallopian tube, or peritoneal cancer that has come back (recurrent). PARPs are proteins that help repair deoxyribonucleic acid (DNA) mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Immunotherapy with monoclonal antibodies, such as tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving olaparib and tremelimumab together may work better than olaparib alone in treating patients with ovarian, fallopian tube, or peritoneal cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Dec 2019
Longer than P75 for phase_2
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 25, 2019
CompletedFirst Posted
Study publicly available on registry
July 29, 2019
CompletedStudy Start
First participant enrolled
December 4, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2021
CompletedResults Posted
Study results publicly available
October 13, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
February 21, 2027
ExpectedApril 13, 2026
February 1, 2026
1.7 years
July 25, 2019
March 13, 2023
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Progression Free Survival (PFS)
The count of participants who have progressed or died (death due to any cause). Progression is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Summary of RECIST 1.1 criteria for progression for this trial: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
PFS is monitored for progression or death due to any cause, whichever occurs first. The median follow-up time is 22 months. Since the study was stopped early, the follow-up for progression-free survival was significantly reduced.
Dose-limiting Toxicity (DLT) (Safety Lead-In)
The outcome measure presents the count of participants who experienced a DLT. If more than six of the first 25 patients treated with Tremelimumab and Olaparib are unable to complete at least 3 cycles of treatment due to DLTs then the study will be stopped. If not, then enrollment will continue until 45 patients are enrolled. If more than 11 of the first 45 patients treated with the combination regimen are unable to complete the first 3 cycles of treatment, then enrollment will be stopped, otherwise, the trial till proceed to the third component (i.e. a phase 2 comparison of study treatments).
At least 4 weeks after initiating treatment, no longer than 12 weeks (three complete treatment cycles). Maximum follow-up was 12 weeks.
Secondary Outcomes (3)
Objective Response (RECIST 1.1)
The median follow-up is 22 months. Since the study was stopped early, the follow-up time frame for objective response was significantly reduced.
Number of Participants Died
Overall survival will be monitored from enrollment to randomization to the date of death due to any cause. The median follow-up is 22 months. Since the study was stopped early, the time frame for OS follow-up was significantly reduced.
Number of Participants With Adverse Event of Grade 3 or Higher
During treatment period and up to 30 days after treatment end. The mean follow-up for adverse events was 6.4 months. Note: survival is monitored for a longer period of time (i.e. up to five years) as compared to the period for collecting adverse events.
Study Arms (2)
Arm I (olaparib)
ACTIVE COMPARATORPatients receive olaparib PO BID in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI as well as blood sample collection throughout the trial.
Arm II (olaparib, tremelimumab)
EXPERIMENTALPatients receive olaparib as in Arm I. Patients also receive tremelimumab IV over 60 minutes on day 1. Cycles of tremelimumab repeat every 4 weeks for 4 doses and then every 12 weeks for up to 2 years total in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI as well as blood sample collection throughout the trial.
Interventions
Undergo blood sample collection
Undergo CT
Undergo MRI
Given PO
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have platinum-sensitive, recurrent high-grade serous or high-grade endometrioid (grade 3) ovarian, primary peritoneal, or fallopian tube cancer. Patients with other histologies are also eligible, provided that the patient has a known deleterious germline or somatic BRCA1 or BRCA2 mutation identified through testing at a clinical laboratory. Submission of BRCA testing results (germline and/or somatic) is required for all patients.
- Platinum-sensitive disease defined as no clinical or radiographic evidence of disease recurrence for \> 6 months (or 182 days) after last receipt of platinum-based therapy. The date should be calculated from the last administered dose of platinum therapy.
- Patients must have had response (complete or partial) to their prior line of platinum therapy and cannot have had progression through prior platinum-based therapy.
- Patients must have RECIST 1.1 measurable disease. Patients with biochemical recurrence based on CA125 levels alone are not eligible.
- Prior therapy:
- Prior chemotherapy must have included a first-line platinum-based regimen with or without consolidation chemotherapy.
- Prior bevacizumab therapy as a component of frontline or recurrent treatment is permitted.
- Patients may have received an unlimited number of platinum-based therapies in the recurrent setting.
- Patients may have received up to one non-platinum-based line of therapy in the recurrent setting. Prior hormonal therapy will not be counted as this non-platinum-based line.
- Prior treatment with a PARP inhibitor:
- Patients may not have had a prior PARP inhibitor in the recurrent setting.
- Prior use of a PARP inhibitor in the upfront maintenance setting is allowed for women with a confirmed BRCA1 or BRCA2 germline or somatic mutation.
- Women who received a PARP inhibitor for maintenance therapy in the frontline setting must have received at least one other chemotherapy regimen for recurrence prior to enrolling on this trial.
- Patients who demonstrated disease progression while on a PARP inhibitor are excluded.
- Prior hormonal-based therapy for ovarian, primary peritoneal, or fallopian tube cancer is acceptable.
- +20 more criteria
You may not qualify if:
- Active infection requiring antibiotic therapy (except for uncomplicated urinary tract infections), including tuberculosis.
- Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; and cirrhosis. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- Hormonal therapy directed at treatment for the cancer must be discontinued at least 28 days prior to enrollment. Hormone replacement therapy for symptom management is permitted.
- Any other therapy directed at treating the cancer including chemotherapy, biologic/targeted agents, and immunologic agents, unless discontinued at least 28 days prior to enrollment.
- Any radiation therapy unless discontinued at least 28 days prior to enrollment.
- Major surgical procedure within 28 days prior to enrollment.
- Current or prior use of immunosuppressive medication within 14 days before enrollment. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (i.e. intra-articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10mg/day of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (i.e. computed tomography \[CT\] scan contrast allergy premedication).
- Patients with active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Patients with autoimmune disease (e.g., psoriasis, extensive atopic dermatitis, severe asthma, inflammatory bowel disease \[IBD\], multiple sclerosis \[M.S.\], uveitis, vasculitis) requiring concurrent use of any systemic immunosuppressants or steroids are excluded from the study. Patients with vitiligo, mild, intermittent asthma requiring only occasional beta-agonist inhaler use, or mild localized eczema are eligible.
- Any patient with an allogeneic (allo)-transplant of any kind is excluded, including xenograft heart valve.
- Chronic use of immune-suppressive drugs (i.e. systemic corticosteroids) for the management of cancer or non-cancer related illnesses (i.e. chronic obstructive pulmonary disease \[COPD\]).
- Note: ongoing steroid use for the management of brain metastases is not permitted.
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Cancer Institute (NCI)lead
- NRG Oncologycollaborator
Study Sites (20)
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
Hartford Hospital
Hartford, Connecticut, 06102, United States
Augusta University Medical Center
Augusta, Georgia, 30912, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
UHHS-Chagrin Highlands Medical Center
Beachwood, Ohio, 44122, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Women and Infants Hospital
Providence, Rhode Island, 02905, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Christopher Purdy on behalf of Danielle Enserro, PhD
- Organization
- NRG Oncology
Study Officials
- PRINCIPAL INVESTIGATOR
Sarah F Adams
NRG Oncology
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 25, 2019
First Posted
July 29, 2019
Study Start
December 4, 2019
Primary Completion
July 31, 2021
Study Completion (Estimated)
February 21, 2027
Last Updated
April 13, 2026
Results First Posted
October 13, 2023
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.