A single-arm phase II study of maintanance treatment of Olaparib, Pembrolizumab, and Bevacizumab in BRCA non-mutated patients with prior platinum-sensitive recurrent ovarian cancer
- Conditions
- Neoplasms
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- Female
- Target Recruitment
- 44
Type of Participant and Disease Characteristics
1) Participant has histologically confirmed diagnosis of high-grade predominantly serous, endometrioid, carcinosarcoma, mixed mullerian with high-grade serous component, clear cell, or low-grade serous OC, primary peritoneal cancer, or fallopian tube cancer will be enrolled in this study (only up to 8 patients with clear cell carcinoma will be included and mucinous carcinoma will not be included).
2) Participant has received 2 previous courses of platinum-containing therapy, and has disease that was considered platinum sensitive following the penultimate (next to last) platinum course (more than 6 months’ period between penultimate platinum regimen and progression of disease)
3) Participant has responded to last the platinum regimen (complete or partial response), remains in response and is enrolled on study within 8 weeks of completion of the last platinum regimen
4) Participant is able to provide a newly obtained core or excisional biopsy of a tumor lesion for prospective testing of BRCA 1/2 and PD-L1 status prior to enrollment
Demographics
5) Female participants who are at least 20 years of age on the day of signing informed consent with
6) Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to enrollment.
Female participants:
7) A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one 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 and olaparib and at least 210 days following the last dose of chemotherapy or bevacizumab.
Information based Consent
8) The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. 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.
Laboratory Values
9) Participant has adequate organ function as defined in the following table
; all screening laboratory tests should be performed within 10 days prior to the start of study treatment.
System Laboratory Value
Hematological
Absolute neutrophil count (ANC) =1500/µL
Platelets =100 000/µL
Hemoglobin =9.0 g/dL or =5.6 mmol/La
Renal
Creatinine OR Measured or calculatedb creatinine clearance (GFR can also be used in place of creatinine or CrCl) =1.5 × ULN OR =30 mL/min for participant with creatinine levels >1.5 × institutional ULN
Hepatic
Total bilirubin =1.5 ×ULN OR direct bilirubin =ULN for participants with total bilirubin levels >1.5 × ULN
AST (SGOT) and ALT (SGPT) =2.5 × ULN (=5 × ULN for participants with liver metastases)
Coagulation
International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT) =1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
Medical Conditions
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 (MDS)/ 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 within the past 3 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ, endometrial carinoma) that have undergone potentially curative therapy are not excluded.
Note: Participants with synchronous primary endometrial cancer or a past history of primary endometrial cancer that met the following conditions are not excluded: Stage not greater than IA: no more than superficial myometrial invasion.
6. Participant has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
7. Participant has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
8. Participant has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
9. Participant has a known history of active TB (Bacillus Tuberculosis).
10. Participant has an active infection requiring systemic therapy.
11. 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 subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
12. Participant has had underwent chemotherapy to treat borderline tumor.
13. Participant has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
14. Participant has a known history of Human Immunodeficiency Virus (HIV).
15. 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. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
16. Participant is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg. Gasterectomy, partial bowel obstruction, malabsorption)
17. Participant has uncontroll
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method progression-free survival
- Secondary Outcome Measures
Name Time Method Overall survival (OS);Time to tumour progression (TTP);Time to first subsequent treatment(or death);Time to second subsequent treatment;progression-free survival