September 9, 2021
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September 16, 2021
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October 20, 2022
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January 1, 2023
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June 1, 2024 (Final data collection date for primary outcome measure)
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Objective response rate (ORR) [ Time Frame: 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.
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Same as current
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- Progression-free survival (PFS) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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] [ Time Frame: 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.
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- Progression-free survival (PFS) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.
- Safety of therapies [ Time Frame: 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.
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Not Provided
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Not Provided
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Biomarker-driven Targeted Therapy in Patients With Recurrent Platinum-resistant Epithelial Ovarian Cancer
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The Efficiency of Biomarker-driven Targeted Therapy in Patients With Recurrent Platinum-resistant Epithelial Ovarian Cancer (PROC): An Umbrella Study
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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).
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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 (Pathological classification: Serous, Endometrioid, and Clear cell Ovarian cancer; Biomarkers: BRCA 1/2 mutant): Pamiparib 40mg PO. bid. plus Bevacizumab 7.5mg/kg IV. D1 (q3w.).
Arm2 (Pathological classification: Serous, Endometrioid, and Clear cell Ovarian cancer; 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 (Pathological classification: Serous, Endometrioid, and Clear cell Ovarian cancer; 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).
Arm4 (Pathological classification: Mucinous Ovarian cancer, Ovarian carcinosarcoma; Biomarkers: ≥3 CD8+ TILs count): Tislelizumab 200mg IV D1 + Bevacizumab 7.5mg/kg IV D1 + Nab-paclitaxel 125mg / m2 IV D1, 8 (q3w).
Arm5 (Pathological classification: Mucinous Ovarian cancer, Ovarian carcinosarcoma; Biomarkers: <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.
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Interventional
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Phase 2
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Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment
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Ovarian Cancer
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- Drug: Pamiparib
40mg PO. bid.
- Drug: Bevacizumab
7.5mg/kg IV. D1 (q3w.)
- Drug: Tislelizumab
200mg IV. D1
- Drug: Nab paclitaxel
125mg / m2 IV. D1, 8 (q3w).
- Drug: Bevacizumab + Nab paclitaxel (intense dose-dense)
Bevacizumab 7.5mg/kg IV. D1, 15 (Q4w). + Nab paclitaxel 100mg / m2 IV. D1, 8, 15 (Q4w).
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- Experimental: Arm 1: Pamiparib+ Bevacizumab
Arm1 (Pathological classification: Serous, Endometrioid, and Clear cell Ovarian cancer; Biomarkers: BRCA 1/2 mutant): Pamiparib 40mg PO. bid. plus Bevacizumab 7.5mg/kg IV. D1 (q3w.).
Interventions:
- Drug: Pamiparib
- Drug: Bevacizumab
- Experimental: Arm 2: Tislelizumab + Bevacizumab + Nab-paclitaxel
Arm2 (Pathological classification: Serous, Endometrioid, and Clear cell Ovarian cancer; 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).
Interventions:
- Drug: Bevacizumab
- Drug: Tislelizumab
- Drug: Nab paclitaxel
- Experimental: Arm 3: Bevacizumab + Nab-paclitaxel
Arm3 (Pathological classification: Serous, Endometrioid, and Clear cell Ovarian cancer; 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).
Intervention: Drug: Bevacizumab + Nab paclitaxel (intense dose-dense)
- Experimental: Arm 4: Tislelizumab + Bevacizumab + Nab-paclitaxel
Arm4 (Pathological classification: Mucinous Ovarian cancer, Ovarian carcinosarcoma; Biomarkers: ≥3 CD8+ TILs count): Tislelizumab 200mg IV D1 + Bevacizumab 7.5mg/kg IV D1 + Nab-paclitaxel 125mg / m2 IV D1, 8 (q3w).
Interventions:
- Drug: Bevacizumab
- Drug: Tislelizumab
- Drug: Nab paclitaxel
- Experimental: Arm 5: Bevacizumab + Nab-paclitaxel
Arm5 (Pathological classification: Mucinous Ovarian cancer, Ovarian carcinosarcoma; Biomarkers: <3 CD8+ TILs count: Bevacizumab 7.5mg/kg IV. D1, 15 + Nab-paclitaxel 100mg / m2 IV. D1, 8, 15 (Q4w).
Intervention: Drug: Bevacizumab + Nab paclitaxel (intense dose-dense)
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Not Provided
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Not yet recruiting
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160
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Same as current
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December 1, 2027
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June 1, 2024 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
- Voluntary participation and signing of informed consent
- Age ≥ 18 years;
- the Eastern United States cancer cooperation group (ECoG) score 0-1;
- 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;
- 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;
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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 about 20 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
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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
- Patients must have lesions that can be measured according to RECIST v1.1 standard;
- Participants were allowed to have previously VEGF / VEGFR inhibitors treatment, but the proportion of these patients would not exceed 20%;
- 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;
- Life expectancy ≥ 3 months;
Exclusion Criteria:
- The exclusion criteria of bevacizumab were clinically significant cardiovascular and cerebrovascular diseases, history of abdominal fistula or gastrointestinal perforation, acute intestinal obstruction or sub obstruction, and active bleeding;
- Uncontrolled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg) or clinically significant (active) cardiovascular disease: cerebrovascular accident (CVA) / stroke ≤ 6 months from the treatment of the first clinical study; Myocardial infarction ≤ 6 months from the first clinical study treatment; Unstable angina pectoris; Congestive heart failure (CHF) of grade II or above in the cardiac function classification standard of the New York Heart Association (NYHA); Serious arrhythmias requiring treatment;
- Previous medical history showed newly discovered thrombotic diseases within 6 months before or during the screening period; Patients with severe wound nonunion, ulcer, or fracture;
- Major surgery within 30 days before the first administration of study treatment; Patients expected to have invasive surgery during treatment;
- Patients with other malignant tumors;
- Patients who have previously received anti-programmed cell death protein-1 (anti-PD-1), anti-programmed death ligand-1 (anti-PD-L1) or anti-PD-L2 drugs, or another drug treatment for T cell inhibitory receptors (e.g., cytotoxic T lymphocyte-associated antigen-4 [CTLA-4], OX-40, CD137 [tumor necrosis factor receptor superfamily member 9 (tnfrsf9)];
- Active autoimmune diseases requiring systemic treatment in the past 2 years;
- Any case requiring systemic treatment with corticosteroids (prednisone or equivalent > 10 mg/day) or other immunosuppressive drugs ≤ 14 days before the first administration of the study drug;
- Known history of human immunodeficiency virus (HIV) infection;
- Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA > 500 IU / ml) or active HCV carriers with detectable HCV RNA; Note: inactive hepatitis B surface antigen (HBsAg) carriers and treated and stable hepatitis B patients (HBV DNA < 500 IU / ml) can be included in the group;
- History of interstitial lung disease, noninfectious pneumonia, or uncontrolled diseases, including pulmonary fibrosis, acute lung disease, etc;
- Previous heterologous stem cell transplantation or organ transplantation;
- Peripheral neuropathy ≥ grade 2;
- Foods or drugs that are expected to use CYP3A4 strong inducers or strong inhibitors within 28 days before the use of the study drug;
- Participate in another clinical study at the same time, unless it is an observational (non-intervention) clinical study or is in the follow-up period of intervention study;
- Women of childbearing age who are unwilling or unable to use effective methods for contraception during the whole treatment period of this trial and within 6 months after the last administration of the study drug [women of childbearing age include: any women who have had menarche and have not undergone successful artificial sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or premenopausal], pregnant or lactating women.
- Other conditions judged by the researcher that do not meet the enrollment requirements.
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Sexes Eligible for Study: |
Female |
Gender Based Eligibility: |
Yes |
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18 Years and older (Adult, Older Adult)
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No
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China
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NCT05044871
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2021-TJ-PROC
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Not Provided
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Studies a U.S. FDA-regulated Drug Product: |
No |
Studies a U.S. FDA-regulated Device Product: |
No |
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Plan to Share IPD: |
Undecided |
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Qinglei Gao, Tongji Hospital
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Same as current
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Tongji Hospital
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Same as current
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- Qilu Hospital of Shandong University
- Hubei Cancer Hospital
- Hunan Cancer Hospital
- Peking University Cancer Hospital & Institute
- Obstetrics and Gynecology Hospital of Zhejiang University
- Sun Yat-sen University
- Anhui Provincial Cancer Hospital
- Jilin Provincial Tumor Hospital
- First Affiliated Hospital, Sun Yat-Sen University
- Affiliated Hospital of Jiangnan University
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Principal Investigator: |
Qinglei Gao, MD. PhD |
Tongji Hospital |
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Tongji Hospital
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October 2022
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