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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

Phase 3
Completed
Conditions
Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cancer
Interventions
Registration Number
NCT03635489
Lead Sponsor
Hoffmann-La Roche
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
100
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Bevacizumab + Paclitaxel + CarboplatinBevacizumabParticipants 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.
Placebo + Paclitaxel + CarboplatinPlaceboParticipants 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.
Bevacizumab + Paclitaxel + CarboplatinPaclitaxelParticipants 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.
Bevacizumab + Paclitaxel + CarboplatinCarboplatinParticipants 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.
Placebo + Paclitaxel + CarboplatinPaclitaxelParticipants 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.
Placebo + Paclitaxel + CarboplatinCarboplatinParticipants 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.
Primary Outcome Measures
NameTimeMethod
Progression-Free Survival (PFS)Randomization up to disease progression or death from any cause, whichever occurs first (up to approximately 24 months)

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.

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS)Randomization up to to death from any cause (up to approximately 54.1 months)

OS was defined as the time from the date of randomization to the date of death from any cause.

Objective Response Rate (ORR)Randomization up to disease progression or death from any cause, whichever occurs first (up to approximately 24 months)

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.

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Abdominal PainFrom randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

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).

Duration of Response (DOR)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)

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.

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported BloatingFrom randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

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).

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Physical)From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

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).

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Role)From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

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).

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Social)From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

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).

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Emotional)From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

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).

Pecentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Health Related Quality of Life (HRQoL)From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

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).

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)

Trial Locations

Locations (16)

the First Hospital of Jilin University

🇨🇳

Changchun, China

Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School

🇨🇳

Nanjing City, China

Tianjin Medical University General Hospital

🇨🇳

Tianjin, China

Beijing Obstetrics and Gynecology Hospital, Capital Medical University

🇨🇳

Beijing City, China

Fujian Cancer Hospital

🇨🇳

Fuzhou, China

Xiangya Hospital Central South University

🇨🇳

Changsha City, China

West China Second University Hospital

🇨🇳

Chengdu City, China

Jilin Cancer Hospital

🇨🇳

Changchun, China

Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department

🇨🇳

Hangzhou City, China

Guangxi Cancer Hospital of Guangxi Medical University

🇨🇳

Nanning, China

Nantong Tumor Hospital

🇨🇳

Nantong City, China

First Affiliated Hospital of Medical College of Xi'an Jiaotong University

🇨🇳

Xi'an, China

Henan Cancer Hospital

🇨🇳

Zhengzhou, China

Harbin Medical University Cancer Hospital

🇨🇳

Harbin, China

Sun Yet-sen University Cancer Center

🇨🇳

Guangzhou City, China

Fudan University Shanghai Cancer Center

🇨🇳

Shanghai City, China

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