Atezolizumab in Combination With Bevacizumab and Chemotherapy Versus Bevacizumab and Chemotherapy in Recurrent Ovarian Cancer - a Randomized Phase III Trial
Overview
- Phase
- Phase 3
- Intervention
- Bevacizumab
- Conditions
- Recurrent Ovarian Carcinoma
- Sponsor
- AGO Research GmbH
- Enrollment
- 574
- Locations
- 109
- Primary Endpoint
- Progression-free survival
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a phase III, randomized, partially blinded, multicenter trial to evaluate the efficacy and safety of atezolizumab plus bevacizumab and chemotherapy compared to placebo plus bevacizumab and chemotherapy in patients with recurrent ovarian-, fallopian tube, or primary peritoneal cancer with 1st or 2nd relapse within 6 months after platinum based chemotherapy or 3rd relapse.
Detailed Description
Approximately 550 patients will be randomized in a 1:1 ratio to the treatments as specified below: Arm A: Chemotherapy + Bevacizumab + Placebo Arm B: Chemotherapy + Bevacizumab + Atezolizumab Study treatment will continue until disease progression per RECIST v1.1, unacceptable toxicity, or patient or investigator decision to discontinue treatment. Atezolizumab/placebo, chemotherapy and bevacizumab may be discontinued for toxicity independently of each other in the absence of disease progression. For each patient, chemotherapy (PLD or Paclitaxel weekly) will be selected by the investigator prior to randomization. Recruitment to an individual chemotherapy cohort will be closed once 50% of patients are recruited to this cohort. In such case the remaining cohort will remain open for recruitment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with histologically diagnosed ovarian, fallopian tube, or primary peritoneal cancer
- •Relapsed disease
- •Patients with up to three prior therapies. In patients with 1 or 2 prior treatment lines, the treatment free interval after platinum has to be less than 6 months; in addition patients with three prior lines of chemotherapy who are not considered for platinum-containing chemotherapy lines are also eligible
- •Measurable disease, evaluable disease in combination with GCIG CA-125 criteria, or histologically proven relapse/progression
- •Mandatory de novo tumor biopsy (not older than 3 months) sent to central laboratory as formalin-fixed, paraffin-embedded (FFPE) sample for determination of PDL1 status prior to randomization for stratification.
- •Availability of a representative archival FFPE tumor sample (preferable from primary diagnosis)
- •Patient has not progressed on the chosen/planned chemotherapy (PLD or Paclitaxel) in any prior line
- •Patients previously treated with bevacizumab are eligible, with the exclusion of those patients that has suspended bevacizumab for more than 2 subsequent cycles or permanently discontinued bevacizumab during their previous treatment due to toxicity.
- •Females aged ≥ 18 years at signing at time of signing informed consent form
- •Signed written informed consent and ability to comply with the study protocol, in the investigator's judgement
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)
- •Malignancies other than ovarian cancer within 5 years prior to randomisation, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%) and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, ductal carcinoma in situ, or Stage I uterine cancer)
- •More than three prior systemic anticancer regimens; maintenance therapies (e.g. with bevacizumab, olaparib or niraparib) are not calculated as separate line.
- •Prior systemic anticancer therapy within 28 days before randomization (except bevacizumab: 20 days).
- •Prior radiotherapy to the pelvis or the abdomen.
- •Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement thera-py is permitted).
- •Prior treatment with anti-CD137 or immune checkpoint blockade therapies, anti-PD1, or anti-PD-L1 therapeutic antibodies or anti-CTLA 4
- •Prior randomization in AGO-OVAR 2.
- •Treatment with systemic immunostimulatory agents (in-cluding but not limited to interferon-alpha (IFN-α) and interleukin-2 (IL-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to cycle 1, day
Arms & Interventions
Arm A: Chemotherapy + Bevacizumab + Placebo
Chemotherapy: Paclitaxel 80 mg/m² d1, 8, 14, 22 q28 or pegylated liposomal doxorubicin 40 mg/m² q28 + Bevacizumab 10 mg/kg q14 + Placebos q14
Intervention: Bevacizumab
Arm A: Chemotherapy + Bevacizumab + Placebo
Chemotherapy: Paclitaxel 80 mg/m² d1, 8, 14, 22 q28 or pegylated liposomal doxorubicin 40 mg/m² q28 + Bevacizumab 10 mg/kg q14 + Placebos q14
Intervention: Chemotherapy
Arm A: Chemotherapy + Bevacizumab + Placebo
Chemotherapy: Paclitaxel 80 mg/m² d1, 8, 14, 22 q28 or pegylated liposomal doxorubicin 40 mg/m² q28 + Bevacizumab 10 mg/kg q14 + Placebos q14
Intervention: Placebos
Arm B: Chemotherapy + Bevacizumab + Atezolizumab
Chemotherapy: Paclitaxel 80 mg/m² d1, 8, 14, 22 q28 or pegylated liposomal doxorubicin 40 mg/m² q28 + Bevacizumab 10 mg/kg q14 + Atezolizumab 840 mg q14
Intervention: Bevacizumab
Arm B: Chemotherapy + Bevacizumab + Atezolizumab
Chemotherapy: Paclitaxel 80 mg/m² d1, 8, 14, 22 q28 or pegylated liposomal doxorubicin 40 mg/m² q28 + Bevacizumab 10 mg/kg q14 + Atezolizumab 840 mg q14
Intervention: Atezolizumab
Arm B: Chemotherapy + Bevacizumab + Atezolizumab
Chemotherapy: Paclitaxel 80 mg/m² d1, 8, 14, 22 q28 or pegylated liposomal doxorubicin 40 mg/m² q28 + Bevacizumab 10 mg/kg q14 + Atezolizumab 840 mg q14
Intervention: Chemotherapy
Outcomes
Primary Outcomes
Progression-free survival
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs earlier, assessed up to 40 months
Progressive Disease based on investigator assessment using RECIST v1.1
Overall Survival (OS)
Time Frame: From date of randomizationrandomization to date of death from any cause assessed up to 40 months
regular patient contacts during the trial regarding life status
Secondary Outcomes
- Efficacy regarding PD-L1 status(From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs earlier, assessed up to 40 months)
- patient reported outcomes (QLQ and PRO-CTCAE)(every 4 weeks during the first 3 months, then every 12 weeks until PD#1, assessed up to 40 months)
- Objective Response Rate (ORR)(From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs earlier, assessed up to 40 months)
- Duration of Response (DOR)(From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs earlier, assessed up to 40 months)