A Phase III Randomised, Double-Blind, Placebo-Controlled, Multicentre Study of Durvalumab in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib in Newly Diagnosed Advanced Ovarian Cancer Patients (DUO-O).
Overview
- Phase
- Phase 3
- Intervention
- Bevacizumab
- Conditions
- Advanced Ovarian Cancer
- Sponsor
- AstraZeneca
- Enrollment
- 1407
- Locations
- 1
- Primary Endpoint
- Progression Free Survival (PFS) - in non-tBRCA HRD positive patients
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a Phase III randomised, double-blind, multi-centre study to evaluate the efficacy and safety of durvalumab in combination with standard of care platinum based chemotherapy and bevacizumab followed by maintenance durvalumab and bevacizumab or durvalumab, bevacizumab and olaparib in patients with newly diagnosed advanced ovarian cancer.
Detailed Description
Eligible patients will be those patients with newly diagnosed, histologically confirmed advanced (Fédération Internationale de Gynécologie et d'Obstétrique \[FIGO\] Stage III-IV) ovarian, primary peritoneal cancer and/or fallopian-tube cancer. All patients should be candidates for cytoreductive surgery which could be conducted as immediate upfront primary surgery following diagnosis or can be conducted after initiation of platinum based neoadjuvant chemotherapy. All patients should be eligible to start first line platinum based chemotherapy in combination with bevacizumab. The study aims to evaluate the efficacy and safety of standard of care (SoC) platinum-based chemotherapy and bevacizumab followed by maintenance bevacizumab either as monotherapy, or in combination with durvalumab, or in combination with durvalumab and olaparib. Therefore, this study aims to see which combination allows patients to live longer without the cancer coming back or getting worse. The study is also looking to see which combination makes patients live longer and how the treatment and the cancer affects their quality of life.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female patients with newly diagnosed, histologically confirmed, advanced (Stage III-IV) high grade epithelial ovarian cancer including high grade serious, high grade endometriod, clear cell ovarian cancer or carcinosarcoma, primary peritoneal cancer and / or fallopian-tube cancer
- •Patients must be aged ≥18 years of age. For patients enrolled in Japan that are aged \<20 year
- •All patients should be candidates for cytoreductive surgery either: upfront primary surgery OR plan to undergo chemotherapy with interval debulking surgery
- •Evidence of presence or absence of BRCA1/2 mutation in tumour tissue
- •Mandatory provision of tumour sample for centralised tBRCA testing
- •ECOG performance status 0-1
- •Patients must have preserved organ and bone marrow function
- •Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test
Exclusion Criteria
- •Non-epithelial ovarian cancer, borderline tumors, low grade epithelial tumors or mucinous histology
- •Prior systemic anti-cancer therapy for ovarian cancer
- •Inability to determine the presence or absence of a deleterious or suspected deleterious BRCA mutation
- •Prior treatment with PARP inhibitor or immune mediated therapy
- •Planned intraperitoneal cytotoxic chemotherapy
- •Active or prior documented autoimmune or inflammatory disorders
- •Patients considered a poor medical risk due to a serious, uncontrolled intercurrent illness
- •Clinically significant cardiovascular disease
- •Patients with known brain metastases
- •History of another primary malignancy except for:
Arms & Interventions
Arm 1
Platinum-based chemotherapy in combination with bevacizumab and durvalumab placebo (saline IV infusion) followed by maintenance bevacizumab, durvalumab placebo (saline IV infusion) and olaparib placebo (tablets).
Intervention: Bevacizumab
Arm 1
Platinum-based chemotherapy in combination with bevacizumab and durvalumab placebo (saline IV infusion) followed by maintenance bevacizumab, durvalumab placebo (saline IV infusion) and olaparib placebo (tablets).
Intervention: Placebo olaparib
Arm 1
Platinum-based chemotherapy in combination with bevacizumab and durvalumab placebo (saline IV infusion) followed by maintenance bevacizumab, durvalumab placebo (saline IV infusion) and olaparib placebo (tablets).
Intervention: Durvalumab placebo
Arm 1
Platinum-based chemotherapy in combination with bevacizumab and durvalumab placebo (saline IV infusion) followed by maintenance bevacizumab, durvalumab placebo (saline IV infusion) and olaparib placebo (tablets).
Intervention: Carboplatin+Paclitaxel
Arm 2
Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib placebo.
Intervention: Bevacizumab
Arm 2
Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib placebo.
Intervention: Durvalumab
Arm 2
Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib placebo.
Intervention: Placebo olaparib
Arm 2
Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib placebo.
Intervention: Carboplatin+Paclitaxel
Arm 3
Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib.
Intervention: Bevacizumab
Arm 3
Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib.
Intervention: Durvalumab
Arm 3
Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib.
Intervention: Olaparib
Arm 3
Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib.
Intervention: Carboplatin+Paclitaxel
tBRCAm cohort
Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib. Bevacizumab is optional according to local practice.
Intervention: Bevacizumab
tBRCAm cohort
Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib. Bevacizumab is optional according to local practice.
Intervention: Durvalumab
tBRCAm cohort
Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib. Bevacizumab is optional according to local practice.
Intervention: Olaparib
tBRCAm cohort
Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib. Bevacizumab is optional according to local practice.
Intervention: Carboplatin+Paclitaxel
Outcomes
Primary Outcomes
Progression Free Survival (PFS) - in non-tBRCA HRD positive patients
Time Frame: Approximately 4 years
Defined as time from randomisation to first progression by investigator assessment using modified RECIST 1.1 or death (by any cause in the absence of progression)
Progression Free Survival (PFS) - in all non-tBRCA patients
Time Frame: Approximately 4 years
Defined as time from randomisation to first progression by investigator assessment using modified RECIST 1.1 or death (by any cause in the absence of progression)
Secondary Outcomes
- Progression Free Survival (PFS) - in non-tBRCAm patients(Approximately 4 years)
- Overall Survival (OS) - in non-tBRCA HRD positive patients and in all non-tBRCA patients(Approximately 7 years)
- Second Progression (PFS2) - in non-tBRCAm patients(Approximately 7 years)
- Health-related quality of life - in non-tBRCAm patients(Approximately 4 years)
- Objective Response Rate (ORR) - in non-tBRCAm patients(Approximately 4 years)
- Time to first subsequent therapy (TFST) - in non-tBRCAm patients(Approximately 7 years)
- Pathological Complete Response (pCR) - in non-tBRCAm patients(Approximately 4 years)
- Duration of response (DoR) - in non-tBRCAm patients(Approximately 4 years)
- PFS - in tBRCAm patients(Approximately 4 years)
- Health-related quality of life - in tBRCAm patients(Approximately 4 years)
- Proportion of patients with pCR in patients undergoing IDS - in tBRCAm patients(Approximately 4 years)
- The pharmacokinetics (PK) and immunogenicity of durvalumab and olaparib as determined by peak concentration - in non-tBRCAm patients(Approximately 4 years)
- Time to discontinuation or death (TDT) - in non-tBRCAm patients(Approximately 4 years)
- Duration of response (DoR) - in tBRCAm patients(Approximately 4 years)
- Time to first subsequent therapy (TFST) - in tBRCAm patients(Approximately 7 years)
- PFS2 - in tBRCAm patients(Approximately 7 years)
- ORR - in tBRCAm patients(Approximately 4 years)
- Time to second subsequent therapy (TSST) - in non-tBRCAm patients(Approximately 7 years)
- ORR pre-surgery in IDS group - in tBRCAm patients(Approximately 4 years)
- Time to second subsequent therapy (TSST) - in tBRCAm patients(Approximately 7 years)
- Time to discontinuation or death (TDT) - in tBRCAm patients(Approximately 4 years)