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)
Overview
- Phase
- Phase 2
- Intervention
- Niraparib
- Conditions
- Ovarian Neoplasms
- Sponsor
- Tesaro, Inc.
- Enrollment
- 77
- Locations
- 1
- Primary Endpoint
- Number of Participants Enrolled Across Cohorts
- Status
- Completed
- Last Updated
- 9 months ago
Overview
Brief 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. Cohort B will not be initiated. Cohort C (randomized-2 arms) includes participants with newly diagnosed ovarian cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant must be female greater than or equal to (\>=)18 years of age, able to understand the study procedures, and agree to participate in the study by providing written informed consent.
- •Participants must have the following histologic diagnosis unless otherwise specified in a cohort-specific supplement:
- •Phase 2 cohorts: Participant has histologically diagnosed high-grade recurrent epithelial (that is \[i.e.\], serous, endometrioid, mucinous, clear cell) ovarian, fallopian tube, or primary peritoneal cancer or carcinosarcoma of the ovary. Participant with high-grade mixed histology is also eligible.
- •For the Phase 1B components: Participant has histologically diagnosed gynecologic malignancy (i.e., any cancer that started in a woman's reproductive system). Gynecologic malignancies include cervical cancer; endometrial cancer; vaginal cancer; vulvar cancer; high-grade recurrent epithelial (i.e., serous, endometrioid, mucinous, clear cell) ovarian, fallopian tube, or primary peritoneal cancer; or advanced carcinosarcoma of the ovary. Participant with high-grade mixed histology is also eligible.
- •The allowed number of prior lines of anticancer therapy for primary cancer will be specified in each cohort-specific supplement. Treatment with hormonal agents alone are not counted in the number of lines of therapy. Treatment with single-agent bevacizumab or PARP inhibitors given as maintenance is not counted as a separate line of therapy. If a therapeutic regimen is modified or changed for a reason other than lack of response or PD (such as allergic reaction, toxicity, or drug availability), this is not counted as a separate line of therapy.
- •Phase 2 cohorts: Participant must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.
- •Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Participant has adequate organ function, defined as follows:
- •Absolute neutrophil count \>=1500 per microliter (/mcL), without growth factor support (granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor administration is not permitted within 2 weeks prior to screening).
- •Platelets \>=100,000/mcL without platelet transfusion support within 2 weeks prior to screening.
Exclusion Criteria
- •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.
- •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.
Arms & Interventions
Cohort A: 1-2 prior lines of therapy (TSR-042, Bevacizumab, and Niraparib)
PARP 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.
Intervention: Niraparib
Cohort A: 1-2 prior lines of therapy (TSR-042, Bevacizumab, and Niraparib)
PARP 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.
Intervention: TSR-042
Cohort A: 1-2 prior lines of therapy (TSR-042, Bevacizumab, and Niraparib)
PARP 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.
Intervention: Bevacizumab
Cohort C: Arm 1: Participants receiving platinum plus taxane
Participants 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.
Intervention: Paclitaxel
Cohort C: Arm 1: Participants receiving platinum plus taxane
Participants 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.
Intervention: Niraparib
Cohort C: Arm 1: Participants receiving platinum plus taxane
Participants 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.
Intervention: Bevacizumab
Cohort C: Arm 1: Participants receiving platinum plus taxane
Participants 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.
Intervention: Carboplatin
Cohort C: Arm 2: Participants receiving neoadjuvant Niraparib
Participants 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.
Intervention: Niraparib
Cohort C: Arm 2: Participants receiving neoadjuvant Niraparib
Participants 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.
Intervention: Bevacizumab
Outcomes
Primary Outcomes
Number of Participants Enrolled Across Cohorts
Time Frame: Day 1
Number of Participants enrolled across cohorts are presented.