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 |
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Recruitment Status :
Completed
First Posted : January 31, 2017
Results First Posted : February 17, 2023
Last Update Posted : February 17, 2023
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Sponsor:
Hoffmann-La Roche
Collaborators:
GOG Foundation
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Information provided by (Responsible Party):
Hoffmann-La Roche
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ovarian Cancer Fallopian Tube Cancer Peritoneal Neoplasms | Drug: Paclitaxel Drug: Carboplatin Drug: Atezolizumab Drug: Bevacizumab Drug: Atezolizumab Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1301 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Actual Study Start Date : | March 8, 2017 |
| Actual Primary Completion Date : | February 8, 2022 |
| Actual Study Completion Date : | August 12, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Ovarian cancer
MedlinePlus related topics:
Ovarian Cancer
| Arm | Intervention/treatment |
|---|---|
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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.
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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 |
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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.
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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: 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 |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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 ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03038100
Locations
Show 268 study locations
Sponsors and Collaborators
Hoffmann-La Roche
GOG Foundation
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
Study Documents (Full-Text)
Documents provided by Hoffmann-La Roche:
Documents provided by Hoffmann-La Roche:
Study Protocol [PDF] November 22, 2021
Statistical Analysis Plan [PDF] December 6, 2021
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT03038100 |
| Other Study ID Numbers: |
YO39523 2016-003472-52 ( EudraCT Number ) |
| First Posted: | January 31, 2017 Key Record Dates |
| Results First Posted: | February 17, 2023 |
| Last Update Posted: | February 17, 2023 |
| Last Verified: | February 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Fallopian Tube Neoplasms Peritoneal Neoplasms Neoplasms by Site Neoplasms Adnexal Diseases Genital Diseases, Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Genital Neoplasms, Female Urogenital Neoplasms Genital Diseases Fallopian Tube Diseases Abdominal Neoplasms Digestive System Neoplasms |
Digestive System Diseases Peritoneal Diseases Paclitaxel Bevacizumab Carboplatin Atezolizumab Antibodies, Monoclonal Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Angiogenesis Inhibitors |