A Randomized, Double-blinded, Phase III Study of Atezolizumab Versus Placebo in Patients With Late Relapse of Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer Treated by Platinum-based Chemotherapy and Bevacizumab
Overview
- Phase
- Phase 3
- Intervention
- placebo + avastin + platinum-based chemotherapy
- Conditions
- Ovarian Cancer
- Sponsor
- ARCAGY/ GINECO GROUP
- Enrollment
- 614
- Locations
- 75
- Primary Endpoint
- Efficacy: Progression free survival, where the date of progression is based on investigator assessment using the RECIST version 1.1
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a phase III, randomized, double-blinded, comparative, multi-centre study to assess the efficacy of atezolizumab in combination with platinum-based chemotherapy plus bevacizumab administered concurrent to chemotherapy and in maintenance, in patients presenting epithelial ovarian cancer (including patients with primary peritoneal and / or fallopian tube adenocarcinoma) who have platinum-sensitive relapse (platinum-free interval > 6 months).
Detailed Description
Approximately 600 patients will be randomized using an Interactive Voice Response System /Interactive web system (IVR/IWR system) in a 1:2 ratio to the treatments as specified below: A. Arm A: Placebo + bevacizumab \& platinum-based chemotherapy. The placebo arm will include one of 3 following regimens up to investigator choice (chosen prior to randomization) 1. Carboplatin (day1)combined with gemcitabine (day1 \& day8) and bevacizumab (day1) + placebo ( day1) x 6 cycles q3weeks followed by maintenance with bevacizumab ( day1) + placebo (day1) q3weeks until disease progression or 2. Carboplatin (d1) combined with paclitaxel (day1) and bevacizumab (day1) + placebo (d1) x 6 cycles every 3weeks followed by maintenance with bevacizumab (day1) + placebo (day1) q3weeks until disease progression or 3. Carboplatin (day1) combined with pegylated liposomal doxorubicin (PLD) (day1) and bevacizumab (day1 \& 15) + placebo ( day1\& 15) x 6 cycles every 4weeks followed by maintenance with bevacizumab (day1) + placebo (day1) q3weeks until disease progression. B. Arm B: Atezolizumab + bevacizumab \& platinum-based chemotherapy The atezolizumab arm will include one of 3 following regimens up to investigator choice (chosen prior to randomization) 1. Carboplatin (day1) combined with gemcitabine (day1 \& d8) and bevacizumab (day1) + atezolizumab ( day1) x 6 cycles q3weeks followed by maintenance with bevacizumab (day1) + atezolizumab (day1) q3w until disease progression or 2. Carboplatin (day1) combined with paclitaxel (day1) and bevacizumab ( day1) + atezolizumab (1200mg, d1) x 6 cycles every 3wk (day1) q3weeks until disease progression or 3. Carboplatin (day1) combined with pegylated liposomal doxorubicin (PLD) (day1) and bevacizumab (day1 \& 15) + atezolizumab (day1\& 15) x 6 cycles every 4weeks followed by maintenance with bevacizumab (day1) + atezolizumab ( day1) q3weeks until disease progression. Before randomization to the study: * A tumor biopsy should have been obtained and sent to the central laboratory * PD-L1 status should be determined
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female Patients must be ≥18 years of age.
- •Signed informed consent and ability to comply with treatment and follow-up.
- •Patients with histologically confirmed progressive non-mucinous epithelial ovarian cancer, primary peritoneal adenocarcinoma and / or fallopian-tube adenocarcinoma
- •Patients with PD-L1 status determined for stratification on mandatory de novo biopsy sent to central laboratory as a formalin-fixed, paraffin-embedded (FFPE) sample.
- •Cell pellet from pleural effusion, or ascites or lavage are not acceptable.
- •For core needle biopsy specimens, at least three cores should be obtained. Biopsies must be obtained in a manner that minimizes risks. If the location of the tumor renders tumor biopsy medically unsafe or not feasible, patient eligibility should be discussed with the sponsor.
- •Patients whose disease has relapsed more than 6 months from the last dose of platinum before randomization:
- •criterion for relapse can be according to RECIST v1.1, CA-125 (GCIG) or clinical symptoms
- •the interval between last dose of platinum and entry in the study should be free of new anti-cancer treatment, with the exception of a maintenance therapy which is allowed up to 21 days before study entry.
- •Patients with one or 2 prior lines of chemotherapy. The last line of chemotherapy should have included platinum.
Exclusion Criteria
- •Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors).
- •Ovarian tumors of low malignant potential (e.g. borderline tumors)
- •Patients with synchronous primary endometrial cancer unless both of the following criteria are met:
- •stage \< II,
- •Less than 60 years old at the time of diagnosis of endometrial cancer with stage IA or IB grade 1 or 2, or stage IA grade 3 endometrioid adenocarcinoma OR ≥ 60 years old at the time of diagnosis of endometrial cancer with stage IA grade 1or 2 endometrioid adenocarcinoma.
- •Patients with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium are not eligible.
- •Other malignancy within the last 5 years except cervix or breast in situ carcinoma, breast cancer ≥ 3 years free of disease and treatment, type I stage I endometrial cancer).
- •Patients receiving radiotherapy within 6 weeks prior to study treatment.
- •Major surgery within 4 weeks of starting study treatment or patients who have not completely recovered from the effects of any major surgery. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1, Cycle 1
- •Previous allogeneic bone marrow transplant or previous solid organ transplantation.
Arms & Interventions
Arm A: Placebo + Avastin + platinum-based chemotherapy
The placebo arm: Placebo 1200 mg x 6 cycles q3wk or 800mg x 6 cycles q4wk during treatment with chemotherapy and Avastin, followed by placebo 1200mg q3wk until progression
Intervention: placebo + avastin + platinum-based chemotherapy
Arm B: Atezolizumab + Avastin+ platinum-based chemotherapy
The atezolizumab arm: Atezolizumab 1200 mg x 6 cycles q3wk or 800mg x 6 cycles q4wk during treatment with chemotherapy and Avastin, followed by atezolizumab 1200mg q3wk until progression .
Intervention: atezolizumab + avastin + platinum-based chemotherapy
Outcomes
Primary Outcomes
Efficacy: Progression free survival, where the date of progression is based on investigator assessment using the RECIST version 1.1
Time Frame: An average of 19 months
Secondary Outcomes
- patient reported outcome variables(to be assessed 19 months)
- Efficacy: Overall survival (OS)(To be assessed around 73 months)
- Efficacy: Time from date randomization to second subsequent therapy or date of death (TSST) whichever come first(To be assessed around 73 months)
- Adverse events(to be assessed 19 months)