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Ovarian NeoplasmsPhase 2OPALNCT03574779

A Study to Evaluate the Efficacy and Safety of Novel Treatment Combinations in Participants With Ovarian Cancer

A Phase 2 study testing Niraparib, TSR-042 and Bevacizumab in people with Ovarian Neoplasms, run by Tesaro, Inc. at 28 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will evaluate the efficacy and safety of niraparib and novel treatment combinations of niraparib as described within each cohort-specific supplement in participants with ovarian, fallopian tube, or primary peritoneal cancer. Cohort A (single arm) includes participants with recurrent ovarian cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Ovarian Neoplasms
What is being tested?
Niraparib, TSR-042 and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
77 participants
Where
28 sitesin 3 countries
Study dates
15 Nov 2018to 31 Mar 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must be resistant to the most recent platinum-based therapy, defined for the purpose of this protocol as progression within 6 months from completion of a minimum of 4 cycles of platinum-containing therapy. This should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing disease progression. Participants with primary platinum-refractory disease as defined by those who progressed during or within 4 weeks of completion of first platinum-based chemotherapy are not eligible.
  • Participant must not have received any prior therapy for ovarian cancer with a PARP inhibitor
  • Participant has had 1 to 2 prior lines of anticancer therapy for ovarian cancer
  • Participant is able to take oral medications.
  • Participant has newly diagnosed Stage III or IV ovarian, fallopian tube, or primary peritoneal cancer according to the International Federation of Gynecology and Obstetrics staging criteria.
  • Participant must provide sufficient tumor tissue at Prescreening and agree to undergo a central HRD tumor testing using a fully validated assay. The tumor must be HRd as per central HRD tumor testing. If central testing does not confirm tumor HRd, the participant will not be eligible for the study.
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  • Participants with documented germline breast cancer gene (BRCA)1/2 deleterious or suspected deleterious mutations by approved test (e.g., BRAC Analysis companion diagnostic [CDx]) will be eligible but will require central HRD testing. Participants with local, academic, or university-based germline BRCA1/2 testing will not be allowed to enroll without results of central HRD test.
  • All participants must agree to provide tumor tissue collected from IDS.
  • Participant must provide 2 formalin-fixed paraffin-embedded tissue blocks (or slides if blocks are not available) with sufficient tumor content (as confirmed by the sponsor's designated central and/or testing laboratory) for central HRD testing at Prescreening and for exploratory biomarker testing at Prescreening or Screening. If sufficient tumor tissue is provided at Prescreening, participants do not need to provide additional tissue at Screening.
  • Participant must have completed 1 run-in cycle of carboplatin-paclitaxel and not experienced disease progression after this treatment. Completion is defined as receiving >=50% of the prescribed dose of therapy within 5 weeks.
  • Participant must not have known contraindication or uncontrolled hypersensitivity to carboplatin and paclitaxel and their excipients and no known pre-existing conditions that would preclude treatment with these agents.
  • Participant must not have known contraindication or uncontrolled hypersensitivity to niraparib and its excipients.
  • Participant must not have symptomatic ascites or pleural effusions as defined by the following criterion: presence of fluid in the abdominal or pleural cavities requiring removal within 1 week prior to signing the informed consent.
  • Participant must agree to complete patient-reported outcomes (PRO) and work productivity questionnaires throughout the study.

Who cannot join

  • Participant has not recovered (i.e., to Grade <=1 or to Baseline) from prior chemotherapy-induced adverse events (AEs).
  • Participant has a known diagnosis of immunodeficiency or is receiving systemic steroid therapy exceeding an equivalent of prednisone 10 mg daily or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
  • Participant is currently participating in a treatment study or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment.
  • Participant has received prior systemic anticancer therapy including cytotoxic chemotherapy, PARP inhibitor, immune checkpoint inhibitors, hormonal therapy given with the intention to treat cancer, or biological therapy within 3 weeks of the first dose of study treatment. This washout period is required to ensure prior therapy is not confounding the toxicity profile of the investigational study drug or study drug combinations in cohorts.
  • Participant has received live vaccine within 14 days of planned start of study therapy.
  • Participant has symptomatic uncontrolled brain or leptomeningeal metastases. Participant who has untreated brain metastases and who is not symptomatic may enroll if the Investigator feels that treatment of these metastases is not indicated. A scan to confirm the absence of brain metastases is not required. Participant with spinal cord compression may be considered if she has received definitive treatment for this and evidence of clinically stable disease (SD) for 28 days prior to the first dose of study treatment.
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  • Participant had major surgery within 4 weeks of starting the study or participant has not recovered from any effects of any major surgery.
  • Participant has a known additional malignancy that progressed or required active treatment within the last 2 years because reoccurrence of another malignancy would confound interpretation of ORR by RECIST v1.1 criteria. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cancer that is considered to be low risk for progression by the investigator.
  • Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. These include, but are not limited to, Coronavirus disease 2019 (COVID-19), significant cardiovascular disease, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, and any psychiatric disorder that prohibits obtaining informed consent.
  • Participant has a history or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the study, might interfere with the participant's participation for the full duration of the study treatment, or is not in the best interest of the participant to participate.
  • Participant has known active hepatitis B (hepatitis B surface antigen reactive) or hepatitis C (hepatitis C virus ribonucleic acid [qualitative] is detected).
  • Cohort A-specific Exclusion Criteria:
  • Participant has known hypersensitivity to TSR-042, bevacizumab, niraparib, their components, or their excipients.
  • Participant has a known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
  • Participant has 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) is not considered a form of systemic treatment.
  • Participant received prior treatment with an anti-PD-1 or anti-PD-L1 agent.
  • Participant has received prior treatment with anti-angiogenic therapy with the exception of bevacizumab. (Participants who received prior bevacizumab are eligible only if they did not discontinue bevacizumab due to toxicity, as established by the Investigator).
  • Participant has bowel obstruction, had bowel obstruction within the past 3 months, or is otherwise judged by the Investigator to be at high risk for bowel obstruction related to the underlying disease. Participant has any history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic examination or significant bowel involvement on computed tomography scan.
  • Participant has proteinuria as demonstrated by urine protein:creatinine ratio >=1.0 at screening or urine dipstick for proteinuria >=2 (Participants discovered to have >=2 proteinuria on dipstick at Baseline should undergo 24-hour urine collection and must demonstrate <2 gram of protein in 24 hours to be eligible).
  • Participant is at increased bleeding risk due to concurrent conditions (e.g., major injuries or surgery within the past 28 days prior to start of study treatment, history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).
  • Participant has a history of recent major thromboembolic event defined as follows: Pulmonary embolism diagnosed within 3 months of enrollment; and Lower extremity deep venous thrombosis diagnosed within 3 months of enrollment.
  • Participant has low-grade or Grade 1 epithelial ovarian cancer (OC) or mucinous, germ cell, transitional cell, carcinosarcoma, or undifferentiated tumor.
  • Participant has contraindications to surgery.
  • Participant has a bowel obstruction by clinical symptoms or computed tomography (CT) scan, subocclusive mesenteric disease, abdominal or gastrointestinal fistula, gastrointestinal perforation, or intra-abdominal abscess.
  • Participant has any known history or current diagnosis of MDS or AML
  • Participant is at increased bleeding risk due to concurrent conditions (e.g., major injuries or major surgery within the past 28 days prior to the start of study treatment and/or history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).
  • Participant is immunocompromised. Participants with splenectomy are allowed. Participants with known human immunodeficiency virus (HIV) are allowed if they meet all of the following criteria:
  • Cluster of differentiation 4-positive T cell count >=350/microliters and viral load <400 copies/mL ii) No history of acute immunodeficiency syndrome (AIDS)-defining opportunistic infections within 12 months prior to enrollment iii) No history of HIV-associated malignancy for the past 5 years iv) Concurrent antiretroviral therapy as per the most current National Institutes of Health Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV started greater than (>)4 weeks prior to study enrollment
  • Participant received prior treatment for high-grade non-mucinous epithelial ovarian, fallopian tube, or peritoneal cancer (e.g., prior surgery, immunotherapy, anticancer therapy [with the exception of 1 run-in cycle of carboplatin-paclitaxel], or radiation therapy).
  • Participant has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic therapy (e.g., thyroid hormone or insulin).
  • Participant is unable to swallow orally administered medication or has a gastrointestinal disorder likely to interfere with absorption of the study medication.
  • Participant received whole blood transfusions in the 2 weeks prior to entry to the study (packed red blood cells and platelet transfusions are acceptable outside of 2 weeks prior to treatment.

Trial locations and contacts

28 sites in 3 countries.

28 sites in 3 countries

United States19 sites

  • GSK Investigational Site

    Baltimore, Maryland, 27710

  • GSK Investigational Site

    Birmingham, Alabama, 35249

  • GSK Investigational Site

    Boston, Massachusetts, 02114

  • GSK Investigational Site

    Boston, Massachusetts, 02215

  • GSK Investigational Site

    Chicago, Illinois, 60637

  • GSK Investigational Site

    Houston, Texas, 77030

  • GSK Investigational Site

    Los Angeles, California, 90095

  • GSK Investigational Site

    New York, New York, 10029

  • GSK Investigational Site

    Oklahoma City, Oklahoma, 73104

  • GSK Investigational Site

    Rochester, Minnesota, 55905

  • GSK Investigational Site

    Rochester, New York, 14642

  • GSK Investigational Site

    San Francisco, California, 94109

  • GSK Investigational Site

    Scarborough, Maine, 04074

  • GSK Investigational Site

    Seattle, Washington, 98104

  • GSK Investigational Site

    Sioux Falls, South Dakota, 57105

  • GSK Investigational Site

    St Louis, Missouri, 63141

  • GSK Investigational Site

    Stanford, California, 94304

  • GSK Investigational Site

    Tampa, Florida, 33606

  • GSK Investigational Site

    Ventura, California, 93003

Other trials in United States

Spain6 sites

  • GSK Investigational Site

    A Coruña, 15006

  • GSK Investigational Site

    Madrid, 28027

  • GSK Investigational Site

    Madrid, 28033

  • GSK Investigational Site

    Madrid, 28050

  • GSK Investigational Site

    Málaga, 29011

  • GSK Investigational Site

    Pamplona, 31008

Other trials in Spain

Canada3 sites

  • GSK Investigational Site

    Montreal, Quebec, H2X 3E4

  • GSK Investigational Site

    Montreal, Quebec, H4A 3J1

  • GSK Investigational Site

    Ottawa, Ontario, K1H 8L6

Other trials in Canada

About this study

Official title: A Phase 1B/2 Multicohort Umbrella Study to Evaluate the Safety and Efficacy of Novel Treatments And/Or Combinations of Treatments in Participants With Ovarian Cancer (OPAL)

This study will evaluate the efficacy and safety of niraparib and novel treatment combinations of niraparib as described within each cohort-specific supplement in participants with ovarian, fallopian tube, or primary peritoneal cancer. Cohort A (single arm) includes participants with recurrent ovarian cancer. Cohort B will not be initiated. Cohort C (randomized-2 arms) includes participants with newly diagnosed ovarian cancer.

Keywords
Poly-ADP-ribose polymerase (PARP) Inhibitor, Ovarian cancer, Niraparib, Bevacizumab, TSR-042, Neoadjuvant treatment
Medical subject headings
Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NiraparibDrug

    Also called ZEJULA

    Niraparib is a potent, orally active PARP1 and PARP2 inhibitor being developed as a treatment for participants with tumors that harbor defects in the homologous recombination deoxyribonucleic acid (DNA) repair pathway or that are driven by PARP-mediated transcription factors.

  • TSR-042Biological

    TSR-042 is a humanized monoclonal antibody that binds with high affinity to Programmed cell death protein 1 (PD-1) resulting in inhibition of binding to programmed death receptor ligands 1 and 2 (PD-L1 and PD-L2).

  • BevacizumabBiological

    Also called Avastin

    Bevacizumab is an Food Drug and Administration (FDA) approved antiangiogenic recombinant humanized monoclonal Immunoglobulin (Ig) G1 antibody against the vascular endothelial growth factor protein, which has been shown to be efficacious against a variety of different cancer types, including colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma.

  • CarboplatinDrug

    Carboplatin will be infused intravenously over 60 minutes at the prescribed dose of area under the concentration versus time curve of 5 to 6 mg/milliliters (mL) per minute on Day 1 of every 21-day cycle

  • PaclitaxelDrug

    Paclitaxel will be administered intravenously over 180 minutes at the prescribed dose of 175 mg/meter square (m^2) on Day 1 of every 21-day cycle

Study groups in NCT03574779
Study groupRoleWhat they receive
Cohort A: 1-2 prior lines of therapy (TSR-042, Bevacizumab, and Niraparib)ExperimentalPARP Inhibitor-Naive Platinum-Resistant Ovarian Cancer Treatment Cohort with TSR-042, Bevacizumab, and Niraparib. TSR-042 administered 500 milligrams (mg) on Day 1 every 3 weeks (Q3W) for 4 cycles (each cycle is 21 days), followed by 1000 mg every 6 weeks (Q6W) beginning on Cycle 5 Day 1 until progressive disease (PD) or toxicity. Bevacizumab administered 15 milligram per kilogram (mg/kg) every 3 weeks for up to 15 months. Niraparib 200 or 300 mg per day until PD or toxicity.
Receives: Drug: Niraparib; Biological: TSR-042; Biological: Bevacizumab
Cohort C: Arm 1: Participants receiving platinum plus taxaneActive comparatorParticipants are expected to receive 1 run-in cycle (up to 5 weeks) of carboplatin-paclitaxel during pre-screening. After confirmation that the tumor is homologous recombination-deficient (HRd). Participants will then be randomized to three 21-day cycles of platinum-taxane doublet chemotherapy (carboplatin plus paclitaxane). After interval debulking surgery (IDS), all participants will receive up to three 21-day cycles of adjuvant platinum-taxane doublet chemotherapy (and optional bevacizumab for participants deemed high-risk; third cycle is optional) followed by niraparib (and optional bevacizumab or bevacizumab biosimilar for participants deemed high- risk) maintenance treatment.
Receives: Drug: Niraparib; Biological: Bevacizumab; Drug: Carboplatin; Drug: Paclitaxel
Cohort C: Arm 2: Participants receiving neoadjuvant NiraparibExperimentalParticipants are expected to receive 1 run-in cycle (up to 5 weeks) of carboplatin-paclitaxel during pre-screening. After confirmation that the tumor is HRd, participants will be randomized to three 21-day cycles of neoadjuvant niraparib therapy. After IDS, all participants will receive up to three 21-day cycles of adjuvant platinum-taxane doublet chemotherapy (and optional bevacizumab for participants deemed high-risk; third cycle is optional) followed by niraparib (and optional bevacizumab or bevacizumab biosimilar for participants deemed high- risk) maintenance treatment.
Receives: Drug: Niraparib; Biological: Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Enrolled Across Cohorts

    Number of Participants enrolled across cohorts are presented.

    Measured: Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2018
  2. Study start15 Nov 2018
  3. Primary completion28 Jun 2024
  4. Study completion31 Mar 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
77 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03574779
Sponsor's protocol ID
213357
Other IDs
3000-02-005
Acronym
OPAL
Status last verified
Jun 2025
First submitted
14 May 2018
Last updated
15 Jul 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Liu JF, Gaillard S, Wahner Hendrickson AE, Yeku O, Diver E, Gunderson Jackson C, Arend R, Ratner E, Samnotra V, Gupta D, Chung J, Zhang H, Compton N, Baines A, Bacque E, Liu X, Felicetti B, Konecny GE. Niraparib, Dostarlimab, and Bevacizumab as Combination Therapy in Pretreated, Advanced Platinum-Resistant Ovarian Cancer: Findings From Cohort A of the OPAL Phase II Trial. JCO Precis Oncol. 2024 May;8:e2300693. doi: 10.1200/PO.23.00693.

    PubMed 38754056

  • Belotte J, Felicetti B, Baines AJ, YoussefAgha A, Rojas-Espaillat L, Ortiz AG, Provencher D, Vazquez RM, Cortijo LG, Zeng X. Comparing niraparib versus platinum-taxane doublet chemotherapy as neoadjuvant treatment in patients with newly diagnosed homologous recombination-deficient stage III/IV ovarian cancer: study protocol for cohort C of the open-label, phase 2, randomized controlled multicenter OPAL trial. Trials. 2024 May 4;25(1):301. doi: 10.1186/s13063-024-08142-5.

    PubMed 38702828

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Niraparib, TSR-042 and Bevacizumab in people with Ovarian Neoplasms, run by Tesaro, Inc. at 28 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in United States, Spain, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Enrolled Across Cohorts (time frame: Day 1). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03574779, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2025.

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