A study to determine whether the addition of TSR-042, followed by the use of niraparib with TSR-042, delays recurrence of ovarian, primary peritoneal or fallopian tube cancer
- Conditions
- Stage 3 or 4 Non-mucinous epithelial ovarian cancer (serous, endometrial, clear cell, carcinosarcoma, and mixed pathologies)MedDRA version: 20.1Level: PTClassification code 10070907Term: Ovarian cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.1Level: PTClassification code 10070908Term: Ovarian cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]
- Registration Number
- EUCTR2018-000413-20-FR
- Lead Sponsor
- TESARO, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 960
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 non-mucinous epithelial ovarian cancer (serous, endometrial, clear cell, carcinosarcoma, and mixed pathologies) that is Stage III or IV according to the FIGO 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 complete cytoreduction (CC0) resection if they meet the following criteria: aggregate 5 cm extra-pelvic disease during PDS that infiltrates the diaphragm, liver capsule, spleen,pancreas, or stomach as assessed by the investigator.
b. All patients with inoperable Stage III disease.
c. All Stage III patients with macroscopic residual tumor (per Investigator judgement) following PDS.
d. All Stage III patients for whom NACT is planned.
5. Patients must provide a blood sample for ctDNA HRR testing at Screening. The ctDNA HRR testing results will be used for patient stratification. If gBRCAmut (germline BRCAmut) detected by locally approved tests (eg, BRACAnalysis CDx™) is previously documented, the patients can be randomized before ctDNA HRR results are available. However, blood samples are still required at Screening for ctDNA HRR testing.
6. Patient must provide a FFPE tumor tissue sample at Screening for HRD testing.
7. Patients of childbearing potential must have a negative serum or urine pregnancy test (beta human chorionic gonadotropin) within 72 hours 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 (see 0) 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 cells/µL
c. Hemoglobin =9 g/dL
d. Serum creatinine =1.5 × upper limit of normal (ULN) or calculated creatinine clearance =60 mL/min using the Cockcroft Gault equation
e. Total bilirubin =1.5 × ULN or direct bilirubin =1.5 × ULN
f. AST and ALT =2.5 × ULN unless liver metastases are present, in which case they must be =5 × ULN
10. Patients must have an ECOG score of 0 or 1.
11. Patients must have normal BP or adequately treated and controlled hypertension (systolic BP =140 mmHg and/or diastolic BP =90 mmHg).
12. Patients must agree to complete HRQoL questionnaires throughout the study.
13. Patients must be able to take oral medication.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 288
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 672
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 <6 months to enrollment, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident within 6 months).
9. Patient has a bowel obstruction by clinical symptoms or CT scan, subocclusive mesenteric disease, abdominal or gastrointestinal fistula, gastrointestinal perforation, or intra abdominal abscess.
10 Patient receiving bevacizumab as SOC has proteinuria as demonstrated by urine protein:creatinine ratio =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 <2 g of protein in 24 hours to be eligible).
11. Patient has any known history or current diagnosis of MDS or AML.
12. Patient has been diagnosed and/or treated with any therapy for invasive cancer <5 years from study enrollment, completed adjuvant chemotherapy and/or targeted therapy (eg, trastuzumab) less than 3 years from enrollment, or completed adjuvant hormonal therapy less than 4 weeks from enrollment. Patients with definitively treated non invasive malignancies such as cervical carcinoma in situ, ductal carcinoma in situ, Grade 1 or 2, Stage I endometrial cancer, or non melanomatous skin cancer are allowed.
13. Patient is at increased bleeding risk due to concurrent conditions (eg, major injuries or major surgery within the past 28 days prior to start of study treatment and/or history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).
14. Patient is immunocompromised. Patients with splenectomy are allowed. Patients with known human immunodeficiency virus (HIV) are allowed if they meet all of the following criteria:
a. Cluster of differentiation 4 =350/µL and viral load <400 copies/mL
b. No history of acquired immunodeficiency syndrome–defining opportunistic infections within 12 months prior to enrollment
c. No history of HIV associated malignancy for the past 5 years
d. Concurrent anti retroviral therapy as per the most current National Insti
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