Durvalumab Treatment in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib Treatment in Advanced Ovarian Cancer Patients (DUO-O)

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Advanced Ovarian Cancer

Treatments: Drug: Bevacizumab; Drug: Durvalumab placebo; Drug: Olaparib; Drug: Placebo olaparib; Drug: Carboplatin+Paclitaxel; Drug: Durvalumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03737643

D081RC00001

2017-004632-11 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,407 patients

Sex: Female

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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

Key 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,407 participants in 4 patient groups

Arm 1

Active Comparator group

Description:

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).

Treatment:

Drug: Carboplatin+Paclitaxel

Drug: Placebo olaparib

Drug: Durvalumab placebo

Drug: Bevacizumab

Arm 2

Experimental group

Description:

Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib placebo.

Treatment:

Drug: Durvalumab

Drug: Carboplatin+Paclitaxel

Drug: Placebo olaparib

Drug: Bevacizumab

Arm 3

Experimental group

Description:

Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib.

Treatment:

Drug: Durvalumab

Drug: Carboplatin+Paclitaxel

Drug: Olaparib

Drug: Bevacizumab

tBRCAm cohort

Experimental group

Description:

Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib. Bevacizumab is optional according to local practice.

Treatment:

Drug: Durvalumab

Drug: Carboplatin+Paclitaxel

Drug: Olaparib

Drug: Bevacizumab