adenocarcinoma
Conditions
Interventions
Pre-Screening Period
During the Pre-Screening Period, patients may sign a pre-screening informed
consent form consenting to collection of the required tumor tissue sample (a
minimum of 1 formalin fi
Sponsors
TESARO, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: To be considered eligible to participate in this study, all of the following requirements must be met: 1. Patients 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. 2. Patients with a histologically confirmed diagnosis of high-grade nonmucinous epithelial ovarian (serous, endometrioid, clear cell, carcinosarcoma, and mixed pathologies), fallopian tube, or primary peritoneal cancer that is Stage III or IV according to the International Federation of Gynecology and Obstetrics or tumor, node and metastasis staging criteria [ie, American Joint Committee on Cancer]. 3. All patients with Stage IV disease are eligible. This includes those with inoperable disease, those who undergo PDS (CC0 or macroscopic disease), or those for whom NACT is planned. 4. Patients with Stage III are eligible if they meet one or more of the following criteria: a. Stage IIIC patients with CC0 resection if they meet the following criteria: aggregate >=5 cm extra-pelvic disease during PDS as assessed by the Investigator b. All patients with inoperable Stage III disease c. All Stage III patients with macroscopic residual tumor (per Investigator judgment) following PDS d. All Stage III patients for whom NACT is planned. 5. Patient must provide a blood sample for ctDNA HRR testing at Pre-Screening or Screening. 6. Patient must provide sufficient tumor tissue sample (a minimum of 1 FFPE block or slide at Pre-Screening or Screening for PD-L1, homologous recombination deficiency HRD testing. 7. Patients of childbearing potential must have a negative serum or urine pregnancy test (beta human chorionic gonadotropin) within 3 days prior to receiving the first dose of study treatment. 8. Patients must be postmenopausal, free from menses for >1 year, surgically sterilized, or willing to use highly effective contraception to prevent pregnancy or must agree to abstain from activities that could result in pregnancy throughout the study, starting with enrollment through 180 days after the last dose of study treatment. 9. Patients must have adequate organ function, defined as follows (Note: CBC test should be obtained without transfusion or receipt of stimulating factors within 2 weeks before obtaining Screening blood sample): a. Absolute neutrophil count >=1,500/µL b. Platelet count >=100,000/µL c. Hemoglobin >=9 g/dL d. Serum creatinine =60 mL/min using the Cockcroft-Gault equation e. Total bilirubin
Exclusion criteria
Exclusion criteria: Patients will not be eligible for study entry if any of the following criteria are met: 1. Patient has mucinous, germ cell, transitional cell, or undifferentiated tumor. 2. Patient has low grade or Grade 1 epithelial ovarian cancer. 3. Stage III patient with R0 resection after PDS (ie, no macroscopic residual disease, unless inclusion criterion #4a is met). 4. Patient has not adequately recovered from prior major surgery. 5. Patient has a known condition, therapy, or laboratory abnormality that might confound the study results or interfere with the patient*s participation for the full duration of the study treatment in the opinion of the Investigator. 6. Patient is pregnant or is expecting to conceive children while receiving study drug or for up to 180 days after the last dose of study drug. Patient is breastfeeding or is expecting to breastfeed within 30 days of receiving the final dose of study drug (women should not breastfeed or store breastmilk for use, during niraparib treatment and for 30 days after receiving the final dose of study treatment). 7. Patient has known active central nervous system metastases, carcinomatous meningitis, or both. 8. Patient has clinically significant cardiovascular disease (eg, significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, uncontrolled cardiac arrhythmia or unstable angina =1.0 at Screening or urine dipstick for proteinuria >=2 (patients discovered to have >=2 proteinuria on dipstick at baseline should undergo a 24 hour urine collection and must demonstrate =350/µL and viral load
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy Analysis Primary Efficacy Endpoint This study has dual primary efficacy endpoints: PFS in PD-L1 positive patients and PFS in all patients. The primary efficacy endpoint PFS is defined as the time from the date of treatment randomization to the date of first documentation of progression or death by any cause in the absence of progression, whichever occurs first, as determined by the Investigator. Progression will be assessed by RECIST v.1.1 criteria based on Investigator*s assessment. Exploratory Efficacy Endpoint The following exploratory efficacy endpoint will be evaluated: • DpOR defined as the maximal amount of tumor shrinkage observed. DpOR will be assessed per RECIST v1.1 and irRECIST criteria in patients with measurable disease. • PFS in Arm 1 and Arm 2 BRCAwt patients who receive bevacizumab will be assessed per RECIST v1.1. • PFS per Investigator-assessed RECIST v.1.1 criteria in patients with HRR/HRD status Interim Analysis Planned periodic safety analyses will be conducted by the Independent Data Monitoring Committee (IDMC) after 24 randomized patients have completed at least 2 cycles of treatment. Details of safety analyses are placed in the IDMC charter. A second safety analysis will occur when approximately 60 patients in Arm 3 have completed at least 2 cycles of the maintenance treatment. After that, periodic safety review will be conducted every 6 months as determined by the IDMC. Biomarker Analysis Biomarkers related to ovarian cancer, PARP inhibition, and PD 1 therapy may be evaluated (eg, DNA repair deficiency, PD-L1 expression, and immune biomarkers). Immunogenicity Analysis Blood samples for the determination of dostarlimab ADAs will be part of the same blood collections as those taken for the PK assessments. ADAs will be analyzed in a tiered approach using electro chemiluminescence (ie, Screening, confirmation, titer, and neutralizing antibody assay), if appropriate. PK Analysis Blood samples for PK w | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Efficacy Endpoints For both PD-L1 positive and all patients, the following secondary efficacy endpoints will be evaluated: • BICR determined PFS per RECIST v1.1 • PFS, per irRECIST criteria based on Investigator*s assessment • OS, as measured from the date of randomization to the date of death by any cause • The observed change from baseline and time to symptom worsening in the EQ 5D 5L, EORTC QLQ C30, and EORTC QLQ OV28 HRQoL assessments • TFST, defined as the date of randomization in the current study to the start date of the first subsequent anticancer therapy or death • TSST, defined as the date of randomization in the current study to the start date of the second subsequent anticancer therapy or death • PFS2, defined as the time from randomization to the earlier date of assessment of progression on the next anticancer therapy following study treatment or death by any cause as assessed by the Investigator • ORR, defined as the percentage of patients with complete response (CR) or partial response (PR) on study treatment as assessed by RECIST v.1.1 criteria for patients with measurable disease. ORR will also be assessed per irRECIST criteria. • pCR rate, per Investigator assessment, defined as the rate of pathologic complete response as assessed by the evaluation of residual microscopic disease at the time of surgery in neoadjuvant patients • DOR, defined as the time from first documentation of CR or PR until the time of first documentation of PD as assessed by RECIST v.1.1, or death by any cause in the absence of progression, whichever occurs first. DOR will also be assessed per irRECIST criteria. • DCR, defined as the proportion of patients with a best overall response of CR, PR, or stable disease, as assessed by RECIST v.1.1 criteria. DCR will also be assessed per irRECIST criteria. • MPFS, defined as the time from the date of the first maintenance period dose to the date of first documentation of progression or death b | — |
Countries
Netherlands
Outcome results
None listed