First-line chemotherapy plus pembrolizumab and olaparib for BRCA non-mutated advanced EOC
- Conditions
- Advanced epithelial ovarian cancerMedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001973-25-HU
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 1086
1. Participant has histologically confirmed FIGO Stage III or Stage IV EOC (high-grade predominantly serous, endometrioid, carcinosarcoma, mixed mullerian with highgrade serous component, clear cell, or low-grade serous OC), primary peritoneal cancer, or fallopian tube cancer
2. Participant has just completed primary debulking surgery or is eligible for primary or interval debulking surgery. Participant must be randomized within 56 days of primary debulking surgery
3. Participant is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the adjuvant or neoadjuvant setting
4. Participant that is a candidate for neoadjuvant chemotherapy has a CA-125 (kilounits/L):carcinoembryonic antigen (CEA; ng/mL) ratio greater than 25
5. Participant is able to provide a newly obtained core or excisional biopsy of a tumor lesion for prospective testing of BRCA1/2 and PD-L1 status prior to randomization
6. Participant is female and at least 18 years of age on the day of signing informed consent
7. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to initiating chemotherapy in the lead-in period and within 7 days prior to randomization
8. A female participant is eligible to participate if she is not pregnant , not breastfeeding, and at least 1 of the following conditions applies:
a.) Not a woman of childbearing potential (WOCBP)
OR
b.) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days following the last dose of pembrolizumab (or pembrolizumab placebo) and olaparib (or olaparib placebo) and at least 210 days following the last dose of chemotherapy or bevacizumab (if administered)
9. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for future biomedical research; however, the participant may participate in the main study without participating in future biomedical research
10. Participant has adequate organ function; all screening laboratory tests should be performed within 7 days of initiating chemotherapy in the lead-in period. Hematological parameters must be reassessed and adequate after the lead-in period and within 7 days prior to randomization
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 800
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 286
1. Participant has mucinous, germ cell, or borderline tumor of the ovary
2. Participant has a known or suspected deleterious mutation (germline or somatic) in either BRCA1 or BRCA2
3. Participant has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis
4. Participant either has myelodysplastic syndrome (MSD)/acute myeloid leukemia (AML)or has features suggestive of MDS/AML
5. Participant has a known additional malignancy that is progressing or has required active treatment in the last 3 years
6. Participant has ongoing Grade 3 or Grade 4 toxicity, excluding alopecia, following chemotherapy administered during the lead-in period
7. Participant has known active central nervous system metastases and/or carcinomatous meningitis.
8. Participant has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization
9. Participant has an active autoimmune disease that has required systemic treatment in the past 2 years
10. Participant has a known history of active tuberculosis (TB; Bacillus Tuberculosis)
11. Participant has an active infection requiring systemic therapy
12. Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s involvement for the full duration of the study, or is not in the best interest of the participant to be involved, in the opinion of the treating investigator
13. Participant has received colony-stimulating factors within 2 weeks prior to randomization
14. Participant is considered to be of poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection
15. Participant has had surgery to treat borderline tumors, early stage EOC, or fallopian tube cancer <6 months prior to screening
16. Participant has a known psychiatric or substance abuse disorder that would interfere with the ability to cooperate with the requirements of the study
17. Participant has a known history of human immunodeficiency virus (HIV) infection.
18. Participant has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
19. Participant is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption
20. Participant has current, clinically relevant bowel obstruction (including sub-occlusive disease), abdominal fistula or gastrointestinal perforation, related to underlying EOC
21. Participant has a history of hemorrhage, hemoptysis or active gastrointestinal bleeding within 6 months prior to randomization
22. A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of chemotherapy in the lead-in period and within 72 hours prior to randomization, is pregnant or breastfeeding, or is expecting to conceive children within the projected duration of the study.
23. Participant has received prior treatment for advanced or metastatic OC, including radiation or systemic anti-cancer therapy
24. Participant has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
25. Participant has received prior
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