A Study of the Efficacy and Safety of Bevacizumab in Chinese Women With Newly Diagnosed, Previously Untreated Stage III or Stage IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Study Overview
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Brief Summary
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This multicenter, double-blind, 2-arm, randomized study will evaluate the efficacy and safety of bevacizumab plus paclitaxel and caboplatin compared with placebo plus paclitaxel and caboplatin in Chinese participants with newly diagnosed, previously untreated Stage III or Stage IV epithelial ovarian, fallopian tube, or primary peritoneal cancer. Participants whose disease has not progressed after six cycles of paclitaxel and carboplatin with either bevacizumab or placebo will continue treatment with either bevacizumab or placebo until disease progression, unacceptable toxicity, or a maximum of 22 cycles, whichever occurs first.

Official Title
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A Phase III Trial of Carboplatin and Paclitaxel Plus Placebo Versus Carboplatin Paclitaxel Plus Concurrent and Extended Bevacizumab in Chinese Women With Newly Diagnosed, Previously Untreated, Stage III or Stage IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Conditions
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Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer

Intervention / Treatment
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* Drug: Paclitaxel
* Drug: Bevacizumab
* Drug: Carboplatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants receiving a histologic diagnosis of epithelial ovarian cancer (EOC), peritoneal primary carcinoma, or fallopian tube cancer. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Life expectancy of at least 12 weeks. Adequate hematological, liver, renal and neurologic functions. For participants who receive therapeutic anticoagulation: stable anticoagulant regimen. Enrollment between 1 and 12 weeks after initial surgery is performed for the combined purpose of diagnosis, staging, and cytoreduction Exclusion Criteria: Current diagnosis of borderline epithelial ovarian tumor or recurrent invasive epithelial ovarian, primary peritoneal, or fallopian tube cancer treated with surgery only. Prior radiotherapy to any portion of the abdominal cavity or pelvis. Prior chemotherapy for any abdominal or pelvic tumor, including neoadjuvant chemotherapy for ovarian, primary peritoneal, or fallopian tube cancer. Any prior targeted therapy (including, but not limited to, vaccines, antibodies, or tyrosine kinase inhibitors) or hormonal therapy for management of their epithelial ovarian or peritoneal primary cancer. Synchronous primary endometrial cancer. Have a prior history of primary endometrial cancer, except: Stage not greater than Stage IB; no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell, or other International Federation of Gynecological Oncologists (FIGO) Grade 3 lesions. Cancer present within the last 5 years with the exception of non-melanoma-related skin cancers and other specific malignancies or whose previous cancer treatment contraindicates study treatment. Active hepatitis B virus (HBV) infection (chronic or acute) or active hepatitis C virus (HCV) infection. Serious non-healing wounds, ulcers, or bone fractures. Patients with clinically significant cardiovascular disease. Have known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies. Have known sensitivity to any component of paclitaxel. Undergo major surgical procedure within 28 days prior to randomization or anticipated during the course of the study. Have core biopsy or other minor surgical procedures within 7 days prior to the first dose of bevacizumab/placebo. History or evidence of thrombotic disorders within the last 6 months prior to enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab + Paclitaxel + Carboplatin<br>Participants will receive paclitaxel, carboplatin intravenous (IV) infusion on Day 1 of each 21-day cycle for a total of 6 cycles, and bevacizumab IV infusion starting from Cycle 2 for a total of 5 cycles, followed by maintenance therapy bevacizumab for a total of 21 cycles of bevacizumab in the absence of disease progression, unacceptable toxicity, or withdrawal, whichever occurs first. | Drug: Paclitaxel<br>* 175 mg/m^2 IV infusion on Day 1 of each 21-day cycle.<br>Drug: Bevacizumab<br>* 15 mg/kg IV infusion on Day 1 of each 21-day cycle.<br>* Other names: Avastin;Drug: Carboplatin<br>* Area Under the Curve (AUC) of 6 mg/ml/min on Day 1 of each 21-day cycle.<br>|
| Placebo Comparator: Placebo + Paclitaxel + Carboplatin<br>Participants will receive paclitaxel, carboplatin IV infusion on Day 1 of each 21-day cycle for a total of 6 cycles, and placebo IV infusion starting from Cycle 2 for a total of 5 cycles, followed by maintenance therapy placebo for a total of 21 cycles of placebo in the absence of disease progression, unacceptable toxicity, or withdrawal, whichever occurs first. | Drug: Paclitaxel<br>* 175 mg/m^2 IV infusion on Day 1 of each 21-day cycle.<br>Drug: Carboplatin<br>* Area Under the Curve (AUC) of 6 mg/ml/min on Day 1 of each 21-day cycle.<br>Drug: Placebo<br>* Placebo matched to bevacizumab IV infusion on Day 1 of each 21-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS was defined as time from randomization to the first occurrence of disease progression, as assessed by the Investigator using RECIST v1.1, or death from any cause, whichever occurs first. | Randomization up to disease progression or death from any cause, whichever occurs first (up to approximately 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the time from the date of randomization to the date of death from any cause. | Randomization up to to death from any cause (up to approximately 24 months) | 
| Objective Response Rate (ORR) | ORR was defined as the proportion of participants with complete response (CR) or partial response (PR) as assessed by investigator according to RECIST v.1.1. | Randomization up to disease progression or death from any cause, whichever occurs first (up to approximately 24 months) | 
| Duration of Response (DOR) | DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression,as assessed by the Investigator using RECIST v1.1, or death from any cause, whichever occurred first. DOR was evaluated for participants who had a objective response of CR or PR. | From the date of first occurrence of a complete or partial response until disease progression or death from any cause (up to approximately 24 months) | 
| Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Abdominal Pain | A clinically meaningful improvement in patient-reported abdominal pain or bloating was defined as a ≥10-point decrease from the linearly transformed 0-100 point baseline symptom scale score on each of two items from the Abdominal/Gastrointestinal Symptom Scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Ovarian Cancer Module (QLQ-OV28). | From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months) | 
| Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Bloating | A clinically meaningful improvement in patient-reported abdominal pain or bloating was defined as a ≥10-point decrease from the linearly transformed 0-100 point baseline symptom scale score on each of two items from the Abdominal/Gastrointestinal Symptom Scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Ovarian Cancer Module (QLQ-OV28). | From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months) | 
| Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Physical) | A clinically meaningful improvement in patient-reported function and HRQoL was defined as a >10-point increase from the linearly transformed 0-100 point baseline scale score on each of the four functional (physical, role, emotional, social) scales and global health status/HRQoL scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30). | From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months) | 
| Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Role) | A clinically meaningful improvement in patient-reported function and HRQoL was defined as a >10-point increase from the linearly transformed 0-100 point baseline scale score on each of the four functional (physical, role, emotional, social) scales and global health status/HRQoL scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30). | From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months) | 
| Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Social) | A clinically meaningful improvement in patient-reported function and HRQoL was defined as a >10-point increase from the linearly transformed 0-100 point baseline scale score on each of the four functional (physical, role, emotional, social) scales and global health status/HRQoL scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30). | From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months) | 
| Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Emotional) | A clinically meaningful improvement in patient-reported function and HRQoL was defined as a >10-point increase from the linearly transformed 0-100 point baseline scale score on each of the four functional (physical, role, emotional, social) scales and global health status/HRQoL scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30). | From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months) | 
| Pecentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Health Related Quality of Life (HRQoL) | A clinically meaningful improvement in patient-reported function and HRQoL was defined as a >10-point increase from the linearly transformed 0-100 point baseline scale score on each of the four functional (physical, role, emotional, social) scales and global health status/HRQoL scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30). | From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months) | 
| Percentage of Participants With Adverse Events (AEs) |  | From randomization up to 90 days after last dose of study treatment or until initiation of new anti-cancer therapy (up to approximately 76 weeks) |