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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

NCT03038100

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: YO39523
  • SECONDARY ID: 2016-003472-52
  • NCT ID: NCT03038100

Conditions

  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Peritoneal Neoplasms

Interventions

DrugSynonymsArms
PaclitaxelAtezolizumab With Paclitaxel, Carboplatin and Bevacizumab
CarboplatinAtezolizumab With Paclitaxel, Carboplatin and Bevacizumab
AtezolizumabAtezolizumab With Paclitaxel, Carboplatin and Bevacizumab
BevacizumabAtezolizumab With Paclitaxel, Carboplatin and Bevacizumab
Atezolizumab PlaceboPlacebo With Paclitaxel, Carboplatin and Bevacizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Atezolizumab With Paclitaxel, Carboplatin and BevacizumabExperimentalParticipants 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.
  • Paclitaxel
  • Carboplatin
  • Atezolizumab
  • Bevacizumab
Placebo With Paclitaxel, Carboplatin and BevacizumabPlacebo ComparatorParticipants 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.
  • Paclitaxel
  • Carboplatin
  • Bevacizumab
  • Atezolizumab Placebo

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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 55 months)
Safety Issue:
Description:
Measure: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 55 months)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description: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 28 (EORTC QLQ-OV28) Abdominal/Gastrointestinal Symptom Scale (Items 31 and 31).
Measure: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)
Safety Issue:
Description: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).
Measure: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)
Safety Issue:
Description:Clinically-meaningful improvement in patient-reported function and HRQoL will be assessed using EORTC QLQ-C30.
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
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)
Measure: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)
Safety Issue:
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)
Measure:Percentage of Participants With Anti-Drug Antibodies (ADAs) 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)
Safety Issue:
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)

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

February 12, 2018