Ovarian Cancer
Conditions
Keywords
Biomarker-driven, Targeted therapy, Immunotherapy
Brief summary
This study is an open-label, multicenter, umbrella study aimed to evaluate the combined, biomarker-driven, targeted treatment efficiency of Pamiparib, Bevacizumab, Tislelizumab, and Nab-paclitaxel in patients with platinum-resistant recurrent ovarian cancer (PROC).
Detailed description
BRCA1/2 gene status and CD8+ tumor-infiltrating T cell count (CD8 + TILs count) were evaluated as biomarkers using archived tumor tissue samples. Treatment arms were arranged according to pathological diagnosis and biomarker detection results. Arm1 (Biomarkers: BRCA 1/2 mutant): Pamiparib 40mg PO. bid. plus Bevacizumab 7.5mg/kg IV. D1 (q3w.). Arm2 (Biomarkers: BRCA 1/2 wildtype and ≥3 CD8+ TILs count): Tislelizumab 200mg IV. D1 + Bevacizumab 7.5mg/kg IV. D1 + Nab-paclitaxel 125mg / m2 IV. D1, 8 (q3w). Arm3 (Biomarkers: BRCA 1/2 wildtype and \<3 CD8+ TILs count): Bevacizumab 7.5mg/kg IV D1, 15 + Nab-paclitaxel 100mg / m2 IV D1, 8, 15 (Q4w). Treatment would continue until disease progression, intolerable toxicity, death, withdrawal of consent, or sponsor termination of the study, whichever occurs first.
Interventions
DRUGPamiparib
40mg PO. bid.
DRUGBevacizumab
7.5mg/kg IV. D1 (q3w.)
DRUGTislelizumab
200mg IV. D1
DRUGNab paclitaxel
125mg / m2 IV. D1, 8 (q3w).
DRUGBevacizumab + Nab paclitaxel (intense dose-dense)
Bevacizumab 7.5mg/kg IV. D1, 15 (Q4w). + Nab paclitaxel 100mg / m2 IV. D1, 8, 15 (Q4w).
Sponsors
Hubei Cancer Hospital
Union Hospital, Tongji Medical College
Peking University Cancer Hospital & Institute
Anhui Provincial Hospital
Sun Yat-sen University Cancer Center (SUSUCC)
Shandong Cancer Hospital and Institute
The First Affiliated Hospital of Xi 'an Jiaotong University
Fujian Cancer Hospital
Chongqing University Cancer Hospital
Qilu Hospital of Shandong University
Tongji Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Voluntary participation and signing of informed consent 2. Age ≥ 18 years; 3. the Eastern United States cancer cooperation group (ECoG) score 0-1; 4. Platinum-resistant recurrent ovarian cancer (PROC): the patient was diagnosed with platinum-resistant recurrence for the first time. PROC refers to the disease progression that occurred \< 6 months after the last dose of platinum-based chemotherapy. Imaging-based evaluation for the latest recurrence/progression before enrollment was required; 5. Malignant epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer confirmed by histology or cytology, including high-grade serous cancer, low-grade serous cancer, endometrioid cancer, clear cell cancer, mucinous cancer, and carcinosarcoma; 6. Biomarker detection and tumor sample collection meet the following standards: * Patients must provide archived tumor tissue samples (formalin-fixed, paraffin-embedded tumor tissue blocks \[preferred\], or at least 10 unstained tissue sections), except for patients with serous carcinoma, endometrioid carcinoma, clear cell carcinoma and gBRCAm * If the patient has been tested for BRCA1 / 2 gene in the past, only the corresponding test report needs to be provided 7. Sufficient organ functions, which is defined as: * neutrophil absolute value (ANC) ≥ 1.5 × 109/L * platelet count (PLT) ≥ 75 × 10\*9/L * hemoglobin ≥ 9 g / dl * serum creatinine CR \< 1.5 × Upper normal value (ULN) * total serum bilirubin ≤ 1.5 × Upper normal range (ULN) * both aspartate aminotransferase and alanine aminotransferase ≤ 3 × ULN * coagulation function: international normalized ratio (INR) ≤ 1.5; Activated partial prothrombin time (APTT) ≤ 1.5 × ULN 8. Patients must have lesions that can be measured according to RECIST v1.1 standard; 9. Participants were allowed to have previously VEGF / VEGFR inhibitors treatment; 10. Participants were allowed to have previously PARP inhibitors treatment. However, for treatment arm 1 (arm1), the exposure time of PARP inhibitors should ≥ 12 months after first-line chemotherapy or ≥ 6 months after second-line and above chemotherapy; 11. Life expectancy ≥ 3 months;
Exclusion criteria
1. The
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to 3 years | ORR is defined as the proportion of patients with complete response(CR) and partial response(PR) assessed by the investigator in accordance with the RECIST 1.1 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to 3 years | PFS is defined as the time from enrollment to the first imaging disease progression or death (whichever occurs first). Assessed according to RECIST v1.1 by investigator. |
| Overall survival (OS) | Up to 5 years | OS is defined as the time between enrollment and the patient's death due to any cause. |
| Disease control rate (DCR) | Up to 5 years | DCR is defined as the proportion of the patients with complete response, partial remission, and stable disease after treatment. Assessed according to RECIST v1.1 by investigator. |
| Duration of remission (DOR) | Up to 3 years | DOR is defined as the time interval from the first record of disease response to disease progression or death (whichever occurs first). Assessed according to RECIST v1.1 by investigator. |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Up to 5 years | Safety includes the adverse event profile of all drugs included according to the Common Terminology Criteria for Adverse Events version 5.0. |
Countries
China
Outcome results
None listed