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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,301
- 试验地点
- 267
- 主要终点
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Paclitaxel (Drug)
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.
干预措施: Carboplatin (Drug)
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.
干预措施: Atezolizumab (Drug)
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.
干预措施: Bevacizumab (Drug)
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.
干预措施: Paclitaxel (Drug)
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.
干预措施: Carboplatin (Drug)
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.
干预措施: Bevacizumab (Drug)
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.
干预措施: Atezolizumab Placebo (Drug)
结局指标
主要结局
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
时间窗: 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
时间窗: 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 - PD-L1-Positive Subpopulation
时间窗: 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 - ITT Population
时间窗: 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.
次要结局
- 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(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))
- Percentage of Participants Who Achieve a Clinically-Meaningful Improvement in Patient-Reported Function and Health Related Quality of Life (HRQoL) - Neoadjuvant Group(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 Objective Response (OR) Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery Group in ITT Population(From randomization until disease progression or death from any cause (up to approximately 55 months))
- 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(From randomization until disease progression or death from any cause (up to approximately 55 months))
- Percentage of Participants Who Achieve a Clinically-Meaningful Improvement in Patient-Reported Function and HRQoL - Primary Tumor-Reductive Surgery Group(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.)
- Duration of Response Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery (Having Residual Measurable Disease) Group in ITT Population(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))
- Percentage of Participants Who Achieve a Clinically-Meaningful Improvement in Patient-Reported Abdominal Pain and Bloating - Neoadjuvant Group(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 in Patient-Reported Function and HRQoL - Primary Tumor-Reductive Surgery Group(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 Deterioration in Patient-Reported Function and HRQoL - Primary Tumor-Reductive Surgery Group(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 at Least One Adverse Event(From randomization up to approximately 59 months)
- Maximum Serum Concentration (Cmax) of Atezolizumab(Cycle 1 Day 1 post dose and Cycle 3 Day 1 post dose)
- Minimum Serum Concentration (Cmin) of Atezolizumab(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(Baseline to approximately 55 months)