Durvalumab treatment in combination with Chemotherapy and Bevacizumab, followed by maintenance Durvalumab, Bevacizumab and Olaparib Treatment in Advanced Ovarian Cancer patients - DUO-O

Study identifier:D081RC00001

ClinicalTrials.gov identifier:NCT03737643

EudraCT identifier:2017-004632-11

CTIS identifier:2022-502747-35-00

Recruitment Complete

Official Title

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).

Medical condition

Advanced Ovarian cancer

Phase

Phase 3

Healthy volunteers

Study drug

Bevacizumab, Durvalumab, Olaparib, Placebo olaparib, Durvalumab placebo, Carboplatin+Paclitaxel

Sex

Female

Actual Enrollment

1407

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 04 Jan 2019

Primary Completion Date: 18 Sept 2023

Estimated Study Completion Date: 25 May 2028

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jan 2024 by AstraZeneca

Collaborators

European Network of Gynaecological Oncology Trial Groups (ENGOT), GOG Foundation, Inc. (GOG Foundation), Myriad Genetic Laboratories, Inc.

Inclusion and exclusion 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:
- Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study treatment and of low potential risk for recurrence (patients who have received prior adjuvant chemotherapy for early stage breast cancer may be eligible, provided that it was completed ≥3 years prior to registration, and that the patient remains free of recurrent or metastatic disease)
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
- Endometrial cancer FIGO Stage IA, Grade 1 or Grade 2
• Persistent toxicities CTCAE Grade >2 caused by previous cancer therapy
• Patients with a known hypersensitivity to olaparib, durvalumab or any of the excipients of these products and to the combination/comparator agents
• Breast feeding women

No locations available

Arms	Assigned Interventions
Active Comparator: 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).	Drug: Bevacizumab Bevacizumab by intravenous infusion. In tBRCAm cohort bevacizumab is optional according to local practice. Drug: Placebo olaparib Placebo tablets to match olaparib Drug: Durvalumab placebo Matching placebo for intravenous infusion Drug: Carboplatin+Paclitaxel Standard of care chemotherapy
Experimental: Arm 2 Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib placebo.	Drug: Bevacizumab Bevacizumab by intravenous infusion. In tBRCAm cohort bevacizumab is optional according to local practice. Drug: Durvalumab Durvalumab by intravenous infusion Drug: Placebo olaparib Placebo tablets to match olaparib Drug: Carboplatin+Paclitaxel Standard of care chemotherapy
Experimental: Arm 3 Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib.	Drug: Bevacizumab Bevacizumab by intravenous infusion. In tBRCAm cohort bevacizumab is optional according to local practice. Drug: Durvalumab Durvalumab by intravenous infusion Drug: Olaparib Olaparib tablets Drug: Carboplatin+Paclitaxel Standard of care chemotherapy
Experimental: 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.	Drug: Bevacizumab Bevacizumab by intravenous infusion. In tBRCAm cohort bevacizumab is optional according to local practice. Drug: Durvalumab Durvalumab by intravenous infusion Drug: Olaparib Olaparib tablets Drug: Carboplatin+Paclitaxel Standard of care chemotherapy

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Philipp Harter

ENGOT