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

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

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer
• Intervention / Treatment: Drug: Paclitaxel; Drug: Bevacizumab; Drug: Carboplatin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing City, China, 100006
    • Beijing Obstetrics and Gynecology Hospital, Capital Medical University
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Changchun, China, 132013
    • Jilin Cancer Hospital
  • Changsha City, China, 410008
    • Xiangya Hospital Central South University
  • Chengdu City, China, 610066
    • West China Second University Hospital
  • Fuzhou, China, 350014
    • Fujian Cancer Hospital
  • Guangzhou City, China, 510663
    • Sun Yet-sen University Cancer Center
  • Hangzhou City, China, 310022
    • Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Nanjing City, China, 210008
    • Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
  • Nanning City, China, 530021
    • Guangxi Cancer Hospital of Guangxi Medical University
  • Nantong City, China, 226361
    • Nantong Tumor Hospital
  • Shanghai City, China, 200120
    • Fudan University Shanghai Cancer Center
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital
  • Xi'an, China, 710061
    • First Affiliated Hospital of Medical College of Xi'an Jiaotong University
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bevacizumab + Paclitaxel + Carboplatin; Participants will receive paclitaxel, carboplatin intravenous (IV) infusion on Day 1 of each 21-day cycle for a total of 6 cycles. Bevacizumab IV infusion will start at Cycle 2 for 5 cycles, followed by maintenance therapy up to a maximum of 22 cycles or until disease progression, unacceptable toxicity, or withdrawal, whichever occurs first.	Drug: Paclitaxel; 175 mg/m^2 IV infusion on Day 1 of each 21-day cycle.; Drug: Bevacizumab; 15 mg/kg IV infusion on Day 1 of each 21-day cycle.; Other Names: Avastin; Drug: Carboplatin; Area Under the Curve (AUC) of 6 mg/ml/min on Day 1 of each 21-day cycle.
Placebo Comparator: Placebo + Paclitaxel + Carboplatin; Participants will receive paclitaxel, carboplatin IV infusion on Day 1 of each 21-day cycle for a total of 6 cycles. Placebo IV infusion will start at Cycle 2 for 5 cycles, followed by maintenance therapy up to a maximum of 22 cycles or until disease progression, unacceptable toxicity, or withdrawal, whichever occurs first.	Drug: Paclitaxel; 175 mg/m^2 IV infusion on Day 1 of each 21-day cycle.; Drug: Carboplatin; Area Under the Curve (AUC) of 6 mg/ml/min on Day 1 of each 21-day cycle.; Drug: Placebo; Placebo matched to bevacizumab IV infusion on Day 1 of each 21-day cycle.

What is the study measuring?

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
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)
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)
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)
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 54.1 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2018
• Primary Completion (Actual): May 26, 2021
• Study Completion (Actual): May 11, 2023

Study Registration Dates

• First Submitted: August 14, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (Actual): August 17, 2018

Study Record Updates

• Last Update Posted (Actual): October 3, 2024
• Last Update Submitted That Met QC Criteria: June 20, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Peritoneal Diseases; Genital Neoplasms, Female; Adnexal Diseases; Digestive System Neoplasms; Fallopian Tube Diseases; Abdominal Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Fallopian Tube Neoplasms; Peritoneal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Carboplatin; Paclitaxel; Bevacizumab
• Other Study ID Numbers: YO40268

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No