OPAL Master ProtocolPhase 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).OPAL-Supplement CCohort C: Open-Label Phase 2, Randomized, Controlled Multicenter Study Comparing Niraparib Versus Platinum-Taxane Doublet Chemotherapy as Neoadjuvant Treatment in Participants with Homologous Recombination-Deficient Stage III/IV Ovarian Cancer.
- Conditions
- Ovarian cancerMedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 24.0Level: PTClassification code 10084789Term: Homologous recombination deficiency positive advanced ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-005392-39-ES
- Lead Sponsor
- GlaxoSmithKline, S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 84
C1. Participant must be female =18 years of age, able to understand the study procedures, and agree to participate in the study by providing written informed consent.
C2. Participant must have measurable disease according to RECIST v1.1.
C3. Participant has an ECOG performance status of 0 to 2.
C4. Participant has adequate organ function, defined as follows:
a. Absolute neutrophil count =1500/µL, without growth factor support (granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor administration is not permitted within 2 weeks of Screening)
b. Platelets =100,000/µL without platelet transfusion support within 2 weeks prior to Screening
c. Hemoglobin =9 g/dL without transfusion or growth factor (recombinant erythropoietin) within 2 weeks of Screening
d. Serum creatinine =1.5× upper limit of normal (ULN) or calculated creatinine clearance =50 mL/min using Cockcroft-Gault equation
e. Total bilirubin =1.5× ULN, except in participants with Gilbert’s syndrome. Participants with Gilbert’s syndrome may enroll if direct bilirubin is =1.5× ULN.
f. Aspartate aminotransferase and alanine aminotransferase =2.5× ULN, unless liver metastases are present, in which case they must be =5× ULN
g. International normalized ratio or prothrombin time (PT) =1.5× ULN, unless participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
h. Activated PTT =1.5× ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. Participants with known lupus anticoagulant and elevated PTT may be eligible on a case-by-case basis after discussion with the sponsor’s Medical Monitor.
C5. Participant is not pregnant or breastfeeding, and at least 1 of the following conditions apply:
- Is not a woman of childbearing potential (WOCBP), as defined in Appendix 1 in the master protocol.
OR
- Is a WOCBP using a contraceptive method that is highly effective (with a failure rate of <1% per year) with low user dependency, as described in Appendix 1 in the master protocol, during the treatment periods and for at least 180 days after the last dose of study treatment and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relation to the first dose of study treatment.
o A WOCBP must have a negative pregnancy test (highly sensitive urine test or serum test as required by local regulations) within 72 hours before the first dose of study treatment.
If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
C6. 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.
C7. 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.
a. Participants with documented germline BRCA1/2 deleterious or suspected deleterious mutations by approve
C1. Participant has not recovered (i.e., to Grade =1 or to Baseline) from prior chemotherapy induced AEs. Note: Participant with Grade =2 neuropathy or alopecia is an exception to this criterion and may qualify for the study.
C2. 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.
C3. 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.
C4. 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.
Note: For this cohort (Cohort C), this criterion will not apply because the population will include only participants who are eligible for neoadjuvant chemotherapy.
C5. Participant has received live vaccine within 14 days of planned start of study therapy.
C7. Participant had major surgery within 4 weeks of starting the study or participant has not recovered from any effects of any major surgery.
C8. 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.
C9. 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, significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, myocardial infarction, cardiac arrhythmia or unstable angina within 6 months prior to enrollment, New York Heart Association Grade =2 congestive heart failure, uncontrolled hypertension, serious cardiac arrhythmia requiring medication, Grade =2 peripheral vascular disease, and history of cerebrovascular accident within 6 months prior to enrollment), uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, and any psychiatric disorder that prohibits obtaining informed consent.
C10. 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.
C11. Participant has known active hepatitis B (e.g., hepatitis B surface antigen reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid [qualitative] is detected).
C12. Participant has low-grade or Grade 1 epithelial OC or mucinous, germ cell, transitional cell, carcinosarcoma, or undifferentiated tumor.
C13. Participant has contraindications to surgery.
C14. Participant has a bow
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method