A Study of Atezolizumab Versus Placebo in Combination With Paclitaxel, Carboplatin, and Bevacizumab in Participants With Newly-Diagnosed Stage III or Stage IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (IMagyn050)

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ClinicalTrials.gov Identifier: NCT03038100

Recruitment Status : Completed

First Posted : January 31, 2017

Results First Posted : February 17, 2023

Last Update Posted : February 17, 2023

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborators:

GOG Foundation

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Information provided by (Responsible Party):

Hoffmann-La Roche

Tracking Information

First Submitted Date ^ICMJE

January 30, 2017

First Posted Date ^ICMJE

January 31, 2017

Results First Submitted Date ^ICMJE

January 9, 2023

Results First Posted Date ^ICMJE

February 17, 2023

Last Update Posted Date

February 17, 2023

Actual Study Start Date ^ICMJE

March 8, 2017

Actual Primary Completion Date

February 8, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Progression-Free Survival (PFS) Assessed by Investigator as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) - Intent-to-Treat (ITT) Population [ Time Frame: From randomization until disease progression or death from any cause (up to approximately 55 months) ]
Investigator-assessed PFS is defined as the time from randomization to the occurrence of disease progression, as determined by the investigator from tumor assessments per RECIST v1.1, or death from any cause during the study, whichever occurs first.
PFS Assessed by Investigator as Per RECIST v1.1 - Programmed Death-Ligand 1 (PD-L1)-Positive Subpopulation [ Time Frame: From randomization until disease progression or death from any cause (up to approximately 55 months) ]
Investigator-assessed PFS is defined as the time from randomization to the occurrence of disease progression, as determined by the investigator from tumor assessments per RECIST v1.1, or death from any cause during the study, whichever occurs first.
Overall Survival - ITT Population [ Time Frame: From randomization up to death from any cause (up to approximately 59 months) ]
Overall Survival (OS) is defined as the time from randomization to death from any cause.
Overall Survival - PD-L1-Positive Subpopulation [ Time Frame: From randomization up to death from any cause (up to approximately 59 months) ]
Overall Survival (OS) is defined as the time from randomization to death from any cause.

Original Primary Outcome Measures ^ICMJE

Progression-Free Survival (PFS) Assessed by Investigator as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) - Intent-to-Treat (ITT) Population [ Time Frame: From randomization until disease progression or death from any cause (up to approximately 56 months) ]
PFS Assessed by Investigator as Per RECIST v1.1 - Programmed Death-Ligand 1 (PD-L1)-Positive Subpopulation [ Time Frame: From randomization until disease progression or death from any cause (up to approximately 56 months) ]
Overall Survival - ITT Population [ Time Frame: From randomization up to death from any cause ( up to approximately 56 months) ]
Overall Survival - PD-L1-Positive Subpopulation [ Time Frame: From randomization up to death from any cause ( up to approximately 56 months) ]

Change History

Current Secondary Outcome Measures ^ICMJE

Percentage of Participants With Objective Response (OR) Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery Group in ITT Population [ Time Frame: From randomization until disease progression or death from any cause (up to approximately 55 months) ]
OR is defined as either a CR or PR as determined by the investigator with the use of RECIST v1.1 for patients with measurable residual disease after primary surgery.
Percentage of Participants With Objective Response (OR) Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery Group in PD-L1-Positive Population [ Time Frame: From randomization until disease progression or death from any cause (up to approximately 55 months) ]
OR is defined as either a CR or PR as determined by the investigator with the use of RECIST v1.1 for patients with measurable residual disease after primary surgery.
Duration of Response Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery (Having Residual Measurable Disease) Group in ITT Population [ Time Frame: From the date of first occurrence of a confirmed complete or partial response until disease progression or death from any cause (up to approximately 55 months) ]
DOR is defined as the time interval from first occurrence of a CR or PR to the time of disease progression, as determined by the investigator with the use of RECIST v1.1, or death from any cause, whichever comes first for patients with measurable residual disease after primary surgery.
Duration of Response Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery (Having Residual Measurable Disease) Group in PD-L1-Positive Population [ Time Frame: From the date of first occurrence of a confirmed complete or partial response until disease progression or death from any cause (up to approximately 55 months) ]
DOR is defined as the time interval from first occurrence of a CR or PR to the time of disease progression, as determined by the investigator with the use of RECIST v1.1, or death from any cause, whichever comes first for patients with measurable residual disease after primary surgery.
Percentage of Participants Who Achieve a Clinically-Meaningful Improvement in Patient-Reported Abdominal Pain and Bloating - Neoadjuvant Group [ Time Frame: From randomization to the end of treatment/discontinuation (up to approximately 66 weeks), and during follow-up period (up to approximately 55 months). Cycle length=21 days. ]
Clinically-meaningful improvement defined as a >=10-point decrease from the baseline score in patient-reported abdominal pain or bloating will be assessed using European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaires Ovarian Cancer Module 28 (EORTC QLQ-OV28) Abdominal/Gastrointestinal Symptom Scale (Items 31 and 31).
Percentage of Participants Who Achieve a Clinically-Meaningful Improvement in Patient-Reported Function and Health Related Quality of Life (HRQoL) - Neoadjuvant Group [ Time Frame: From randomization to the end of treatment/discontinuation (up to approximately 66 weeks), and during follow-up period (up to approximately 55 months). Cycle length=21 days. ]
Clinically-meaningful improvement in patient-reported function and HRQoL during the treatment period, defined as a >=10-point increase from the baseline score on each of the functional (social, emotional, physical, role) and GHS/QoLscales of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaires Core 30 (EORTC QLQ-C30).
Percentage of Participants Who Achieve a Clinically-Meaningful Improvement in Patient-Reported Function and HRQoL - Primary Tumor-Reductive Surgery Group [ Time Frame: From randomization to the end of treatment/discontinuation (up to approximately 66 weeks), and during follow-up period (up to approximately 55 months). Cycle length=21 days. ]
Percentage of participants with clinical improvement, defined as >= 10-point increase from the baseline score on each of the functional (physical, role, emotional, and social) and GHS/QoL scales of the EORTC QLQ-C30.
Percentage of Participants Who Remain Stable in Patient-Reported Function and HRQoL - Primary Tumor-Reductive Surgery Group [ Time Frame: From randomization to the end of treatment/discontinuation (up to approximately 66 weeks), and during follow-up period (up to approximately 55 months). Cycle length=21 days. ]
Percentage of participants who remain stable defined as changes within 10 points from the baseline score on each of the functional (physical, role, emotional, and social) and GHS/QoL scales of the EORTC QLQ-C30.
Percentage of Participants With Deterioration in Patient-Reported Function and HRQoL - Primary Tumor-Reductive Surgery Group [ Time Frame: From randomization to the end of treatment/discontinuation (up to approximately 66 weeks), and during follow-up period (up to approximately 60 months). Cycle length=21 days. ]
Percentage of participants with deterioration in patient-reported function and HRQoL, defined as >= 10 points decrease from the baseline score on each of the functional (physical, role, emotional, and social) and GHS/QoL scales of the EORTC QLQ-C30.
Percentage of Participants With at Least One Adverse Event [ Time Frame: From randomization up to approximately 59 months ]
Percentage of participants with at least one adverse event.
Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Cycle 1 Day 1 post dose and Cycle 3 Day 1 post dose ]
Minimum Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Cycle 2 Day 1 predose, Cycle 3 Day 1 Predose, Cycle 4 Day 1 predose, Cycle 8 Day 1 predose, Cycle 16 Day 1 predose ]
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Baseline to approximately 55 months ]

Original Secondary Outcome Measures ^ICMJE

Percentage of Participants With Objective Response (OR) Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery (Having Residual Measurable Disease) Group [ Time Frame: From randomization until disease progression or death from any cause (up to approximately 56 months) ]
Duration of Response Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery (Having Residual Measurable Disease) Group [ Time Frame: From the date of first occurrence of a confirmed complete or partial response until disease progression or death from any cause (up to approximately 56 months) ]
Percentage of Participants who Achieve a Clinically-Meaningful Improvement in Patient-Reported Abdominal Pain or Bloating - Neoadjuvant Group [ Time Frame: From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 60 months) ]
Clinically-meaningful improvement in patient-reported abdominal pain or bloating will be assessed using European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaires Ovarian Cancer Module (EORTC QLQ-OV28).
Percentage of Participants who Achieve a Clinically-Meaningful Improvement in Patient-Reported Function and Health Related Quality of Life (HRQoL) - Neoadjuvant Group [ Time Frame: From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 60 months) ]
Clinically-meaningful improvement in patient-reported function and HRQoL will be assessed using European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaires Core 30 (EORTC QLQ-C30).
Percentage of Participants who Achieve a Clinically-Meaningful Improvement, Remain Stable or Deterioration in Patient-Reported Function and HRQoL - Primary Tumor-Reductive Surgery Group [ Time Frame: From randomization to the end of treatment/discontinuation (up to approximately 66 weeks), and during follow-up period (up to approximately 60 months) ]
Clinically-meaningful improvement in patient-reported function and HRQoL will be assessed using EORTC QLQ-C30.
Percentage of Participants With Adverse Events [ Time Frame: From randomization up to 90 days after last dose of study treatment or until initiation of new anti-cancer therapy (up to approximately 82 weeks) ]
Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Pre-infusion (0 hour [hr]), 30 minutes (min) after end of infusion (EOI) on Cycle 1 Day 1(Cycle length=21 days) up to approximately 82 weeks (detailed timeframe is provided in outcome measure description) ]
Primary surgery group: Pre-infusion (0 hr), 30 min after EOI (infusion duration=60 min) on Day 1 of Cycles 1 and 3; pre-infusion (0 hr) on Day 1 of Cycles 2, 4, 8, 16 (each cycle=21 days); end of treatment/discontinuation visit (up to approximately 66 weeks); >/=90 days after last dose (up to approximately 78 weeks) Neoadjuvant therapy group: Pre-infusion (0 hr), 30 min after EOI (infusion duration=60 min) on Day 1 of Cycles 1 and 3; pre-infusion (0 hr) on Day 1 of Cycles 2, 4 (each cycle=21 days); end of treatment/discontinuation visit (up to approximately 70 weeks); >/= 90 days after last dose (up to approximately 82 weeks)
Minimum Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Pre-infusion (0 hr), 30 min after EOI on Cycle 1 Day 1(Cycle length=21 days) up to approximately 82 weeks (detailed timeframe is provided in outcome measure description) ]
Primary surgery group: Pre-infusion (0 hr), 30 min after EOI (infusion duration=60 min) on Day 1 of Cycles 1 and 3; pre-infusion (0 hr) on Day 1 of Cycles 2, 4, 8, 16 (each cycle=21 days); end of treatment/discontinuation visit (up to approximately 66 weeks); >/= 90 days after last dose (up to approximately 78 weeks) Neoadjuvant therapy group: Pre-infusion (0 hr), 30 min after EOI (infusion duration=60 min) on Day 1 of Cycles 1 and 3; pre-infusion (0 hr) on Day 1 of Cycles 2, 4 (each cycle=21 days); end of treatment/discontinuation visit (up to approximately 70 weeks); >/= 90 days after last dose (up to approximately 82 weeks)
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab [ Time Frame: Pre-infusion (0 hr) on Cycle 1 Day 1(Cycle length=21 days) up to approximately 82 weeks (detailed timeframe is provided in outcome measure description) ]
Primary surgery group: Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 16 (each cycle=21 days); end of treatment/discontinuation visit (up to approximately 66 weeks); >/= 90 days after last dose (up to approximately 78 weeks) Neoadjuvant therapy group: Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4 (each cycle=21 days); end of treatment/discontinuation visit (up to approximately 70 weeks); >/= 90 days after last dose (up to approximately 82 weeks)

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

A Study of Atezolizumab Versus Placebo in Combination With Paclitaxel, Carboplatin, and Bevacizumab in Participants With Newly-Diagnosed Stage III or Stage IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Official Title ^ICMJE

A Phase III, Multicenter, Randomized, Study of Atezolizumab Versus Placebo Administered in Combination With Paclitaxel, Carboplatin, and Bevacizumab to Patients With Newly-Diagnosed Stage III or Stage IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Brief Summary

This is a Phase III, global, double-blind, 2-arm randomized study designed to compare the efficacy and safety of atezolizumab + paclitaxel + carboplatin + bevacizumab versus placebo + paclitaxel + carboplatin + bevacizumab. Study participants will have Stage 3 or 4 ovarian cancer (OC), fallopian tube cancer (FTC), or primary peritoneal cancer (PPC) with macroscopic residual disease postoperatively (i.e., after primary tumor reductive surgery) or who will undergo neoadjuvant therapy followed by interval surgery.

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment

Condition ^ICMJE

Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Neoplasms

Intervention ^ICMJE

Drug: Paclitaxel
Paclitaxel 175 milligrams per square meter (mg/m^2) IV infusion on Day 1 of each 21-day cycle
Drug: Carboplatin
Carboplatin at a dose to achieve a target area under the curve (AUC) of 6 milligrams per milliliter*minute (mg/mL*min) on Day 1 of each 21-day cycle for a total of 6 cycles
Drug: Atezolizumab
Atezolizumab 1200 mg IV infusion on Day 1 of each 21-day cycle
Drug: Bevacizumab
Bevacizumab 15 milligrams per kilogram (mg/kg) IV infusion as per the schedule specified in respective arms
Drug: Atezolizumab Placebo
Placebo matching to atezolizumab on Day 1 of each 21-day cycle

Study Arms ^ICMJE

Experimental: Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab
Participants in the primary tumor-reductive surgery group will receive paclitaxel, carboplatin, atezolizumab intravenous (IV) infusion on Day 1 of each 21-day cycle for a total of 6 cycles, and bevacizumab IV infusion starting with Cycle 2 for a total of 5 cycles, followed by maintenance therapy bevacizumab with atezolizumab for a total of 22 cycles of atezolizumab and 21 cycles of bevacizumab. Participants in the neoadjuvant therapy group will receive paclitaxel, carboplatin and atezolizumab for 6 cycles and bevacizumab for 4 cycles. Interval surgery will occur between cycles 3 and 4. Each cycle is 21 days long. After 6 cycles, participants will start maintenance therapy of bevacizumab and atezolizumab for additional 16 cycles.
Interventions:
- Drug: Paclitaxel
- Drug: Carboplatin
- Drug: Atezolizumab
- Drug: Bevacizumab
Placebo Comparator: Placebo With Paclitaxel, Carboplatin and Bevacizumab
Participants in the primary tumor-reductive surgery group will receive paclitaxel, carboplatin, atezolizumab placebo IV infusion on Day 1 of each 21-day cycle for a total of 6 cycles, and bevacizumab IV infusion starting with Cycle 2 for a total of 5 cycles, followed by maintenance therapy bevacizumab with atezolizumab placebo for a total of 22 cycles of atezolizumab placebo and 21 cycles of bevacizumab. Participants in the neoadjuvant therapy group will receive paclitaxel, carboplatin and placebo for 6 cycles and bevacizumab for 4 cycles. Interval surgery will occur between cycles 3 and 4. Each cycle is 21 days long. After 6 cycles, participants will start maintenance therapy of bevacizumab and placebo for additional 16 cycles.
Interventions:
- Drug: Paclitaxel
- Drug: Carboplatin
- Drug: Bevacizumab
- Drug: Atezolizumab Placebo

Publications *

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Actual Enrollment ^ICMJE

1301

Original Estimated Enrollment ^ICMJE

1300

Actual Study Completion Date ^ICMJE

August 12, 2022

Actual Primary Completion Date

February 8, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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 greater than (>) 12 weeks
For participants who receive therapeutic anticoagulation: stable anticoagulant regimen
Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen in paraffin blocks (preferred) or at least 20 unstained slides (for detailed tissue requirements at screening)

Exclusion Criteria:

Received a current diagnosis of borderline epithelial ovarian tumor (formerly tumors of low malignant potential)
Have recurrent invasive epithelial ovarian, fallopian tube, or primary peritoneal cancer that was treated only with surgery (example [e.g.], participants with Stage IA or Stage IB epithelial ovarian or fallopian tube cancers)
Have non-epithelial ovarian tumors (e.g., germ cell tumors, sex cord stromal tumors)
Received prior radiotherapy to any portion of the abdominal cavity or pelvis
Received prior chemotherapy for any abdominal or pelvic tumor that include neoadjuvant chemotherapy (NACT) for ovarian, primary peritoneal or fallopian tube cancer
Received any biological and/or targeted therapy (including but not limited to vaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for management and/or treatment of epithelial ovarian or peritoneal primary cancer
Have synchronous primary endometrial cancer
Have a prior history of primary endometrial cancer, except: Stage IA cancer; superficial myometrial invasion, without lymphovascular invasion; grade less than (<) 3 or poorly differentiated subtypes, and this includes papillary serous, clear cell or other International Federation of Gynecological Oncologists (FIGO) Grade 3 lesions
With the exception of non-melanoma skin cancer and other specific malignancies as noted above, other invasive malignancies with any evidence of other cancers present within the last 5 years or previous cancer treatment that contraindicates this protocol therapy
Have a known hypersensitivity or allergy to biopharmaceutical agents produced in Chinese hamster ovary cells or any component of the atezolizumab and/or bevacizumab formulations
Undergo major surgical procedure within 28 days prior to first bevacizumab dose, or anticipation of the need for a major surgical procedure during the course of the study except participants who receive NACT and will need interval surgery. This may include but is not limited to laparotomy.
Have prior allogeneic bone marrow transplantation or solid organ transplant
Have any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results
Have any approved or investigational anti-cancer therapy, including chemotherapy or hormonal therapy, with exceptions: Hormone-replacement therapy or oral contraceptives
Are administered treatment with any other investigational agent or participation in another clinical study with anti-cancer therapeutic intent
Have core biopsy or other minor surgical procedures within 7 days prior to the first dose of bevacizumab
Have known sensitivity to any component of bevacizumab
Have known sensitivity to any component of paclitaxel
Current treatment with anti-viral therapy for hepatitis B virus (HBV)
History of leptomeningeal disease

Sex/Gender ^ICMJE

Sexes Eligible for Study:

Female

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

Australia, Austria, Belgium, Brazil, China, Czechia, Denmark, Finland, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Norway, Poland, Russian Federation, Spain, Sweden, Turkey, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT03038100

Other Study ID Numbers ^ICMJE

YO39523
2016-003472-52 ( EudraCT Number )

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Not Provided

Current Responsible Party

Hoffmann-La Roche

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

Hoffmann-La Roche

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

GOG Foundation
European Network of Gynaecological Oncological Trial Groups (ENGOT)

Investigators ^ICMJE

Study Director:

Clinical Trials

Hoffmann-La Roche

PRS Account

Hoffmann-La Roche

Verification Date

February 2023

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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