Durvalumab Treatment in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib Treatment in Advanced Ovarian Cancer Patients

NCT ID: NCT03737643

Last Updated: 2025-01-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1407 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-04

Study Completion Date

2028-03-30

Brief Summary

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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

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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.

Conditions

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Advanced Ovarian Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The study consists of 2 independent cohorts: 3 double-blind treatment arms cohort for patients with no tBRCA mutation, and a single open label arm cohort for patients with tBRCA mutation
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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).

Group Type ACTIVE_COMPARATOR

Bevacizumab

Intervention Type DRUG

Bevacizumab by intravenous infusion. In tBRCAm cohort bevacizumab is optional according to local practice.

Placebo olaparib

Intervention Type DRUG

Placebo tablets to match olaparib

Durvalumab placebo

Intervention Type DRUG

Matching placebo for intravenous infusion

Carboplatin+Paclitaxel

Intervention Type DRUG

Standard of care chemotherapy

Arm 2

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

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

Bevacizumab by intravenous infusion. In tBRCAm cohort bevacizumab is optional according to local practice.

Durvalumab

Intervention Type DRUG

Durvalumab by intravenous infusion

Placebo olaparib

Intervention Type DRUG

Placebo tablets to match olaparib

Carboplatin+Paclitaxel

Intervention Type DRUG

Standard of care chemotherapy

Arm 3

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

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

Bevacizumab by intravenous infusion. In tBRCAm cohort bevacizumab is optional according to local practice.

Durvalumab

Intervention Type DRUG

Durvalumab by intravenous infusion

Olaparib

Intervention Type DRUG

Olaparib tablets

Carboplatin+Paclitaxel

Intervention Type DRUG

Standard of care chemotherapy

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.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

Bevacizumab by intravenous infusion. In tBRCAm cohort bevacizumab is optional according to local practice.

Durvalumab

Intervention Type DRUG

Durvalumab by intravenous infusion

Olaparib

Intervention Type DRUG

Olaparib tablets

Carboplatin+Paclitaxel

Intervention Type DRUG

Standard of care chemotherapy

Interventions

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Bevacizumab

Bevacizumab by intravenous infusion. In tBRCAm cohort bevacizumab is optional according to local practice.

Intervention Type DRUG

Durvalumab

Durvalumab by intravenous infusion

Intervention Type DRUG

Olaparib

Olaparib tablets

Intervention Type DRUG

Placebo olaparib

Placebo tablets to match olaparib

Intervention Type DRUG

Durvalumab placebo

Matching placebo for intravenous infusion

Intervention Type DRUG

Carboplatin+Paclitaxel

Standard of care chemotherapy

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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European Network of Gynaecological Oncological Trial Groups (ENGOT)

OTHER

Sponsor Role collaborator

GOG Foundation, Inc. (GOG Foundation)

UNKNOWN

Sponsor Role collaborator

Myriad Genetic Laboratories, Inc.

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Philipp Harter

Role: PRINCIPAL_INVESTIGATOR

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Carol Aghajanian

Role: PRINCIPAL_INVESTIGATOR

GOG

Locations

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Research Site

Foothill Ranch, California, United States

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Los Angeles, California, United States

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Orange, California, United States

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San Francisco, California, United States

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Tampa, Florida, United States

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Augusta, Georgia, United States

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Hinsdale, Illinois, United States

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Indianapolis, Indiana, United States

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Towson, Maryland, United States

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Detroit, Michigan, United States

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Springfield, Missouri, United States

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Middletown, New Jersey, United States

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Montvale, New Jersey, United States

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Albany, New York, United States

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New York, New York, United States

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Uniondale, New York, United States

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Durham, North Carolina, United States

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Cleveland, Ohio, United States

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Dayton, Ohio, United States

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Hilliard, Ohio, United States

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Tulsa, Oklahoma, United States

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Lancaster, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Salt Lake City, Utah, United States

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Graz, , Austria

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Innsbruck, , Austria

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Linz, , Austria

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Vienna, , Austria

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Aalst, , Belgium

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Leuven, , Belgium

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Namur, , Belgium

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Ostend, , Belgium

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Sint-Niklaas, , Belgium

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Barretos, , Brazil

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Florianópolis, , Brazil

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Fortaleza, , Brazil

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Londrina, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Burgas, , Bulgaria

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Calgary, Alberta, Canada

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Barrie, Ontario, Canada

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Greater Sudbury, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Rimouski, Quebec, Canada

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Beijing, , China

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Beijing, , China

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Bengbu, , China

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Changchun, , China

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Changsha, , China

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Changsha, , China

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Chengdu, , China

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Chongqing, , China

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Dalian, , China

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Guangzhou, , China

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Guangzhou, , China

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Hangzhou, , China

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Hangzhou, , China

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Harbin, , China

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Hefei, , China

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Jinhua, , China

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Kunming, , China

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Lanzhou, , China

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Luzhou, , China

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Nanchong, , China

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Nanjing, , China

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Nanning, , China

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Nantong, , China

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Shanghai, , China

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Shanghai, , China

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Wuhan, , China

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Wuhan, , China

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Xi'an, , China

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Zhengzhou, , China

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Zhengzhou, , China

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Zhuhai, , China

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Aalborg, , Denmark

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Aarhus N, , Denmark

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Odense, , Denmark

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Roskilde, , Denmark

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Vejle, , Denmark

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Kuopio, , Finland

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Oulu, , Finland

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Turku, , Finland

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Besançon, , France

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Bordeaux, , France

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Limoges, , France

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Lyon, , France

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Marseille, , France

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Nantes, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Saint-Herblain, , France

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Vandœuvre-lès-Nancy, , France

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Bad Homburg, , Germany

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Berlin, , Germany

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Bielefeld, , Germany

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Bonn, , Germany

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Brandenburg, , Germany

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Cologne, , Germany

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Dresden, , Germany

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Düsseldorf, , Germany

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Essen, , Germany

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Essen, , Germany

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Esslingen am Neckar, , Germany

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Frankfurt, , Germany

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Freiburg im Breisgau, , Germany

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Fürth, , Germany

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Greifswald, , Germany

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Gütersloh, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Hanover, , Germany

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Jena, , Germany

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Karlsruhe, , Germany

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Karlsruhe, , Germany

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Kassel, , Germany

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Kiel, , Germany

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Leipzig, , Germany

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Ludwigsburg, , Germany

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Lübeck, , Germany

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Mainz, , Germany

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Mannheim, , Germany

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München, , Germany

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Offenbach, , Germany

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Oldenburg, , Germany

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Rosenheim, , Germany

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Rostock, , Germany

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Saalfeld, , Germany

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Schweinfurt, , Germany

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Tübingen, , Germany

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Ulm, , Germany

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Worms, , Germany

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Budapest, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Győr, , Hungary

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Kaposvár, , Hungary

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Szeged, , Hungary

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Zalaegerszeg, , Hungary

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Brescia, , Italy

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Lecce, , Italy

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Lecco, , Italy

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Milan, , Italy

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Milan, , Italy

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Mirano, , Italy

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Napoli, , Italy

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Reggio Calabria, , Italy

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Reggio Emilia, , Italy

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Roma, , Italy

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Torino, , Italy

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Torino, , Italy

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Fukuoka, , Japan

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Kashiwa-shi, , Japan

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Kobe, , Japan

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Kōtoku, , Japan

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Kurume-shi, , Japan

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Kyoto, , Japan

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Minatoku, , Japan

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Nagoya, , Japan

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Niigata, , Japan

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Okayama, , Japan

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Sapporo, , Japan

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Sendai, , Japan

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Shinjuku-ku, , Japan

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Sunto-gun, , Japan

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Toyoake-shi, , Japan

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Bellavista, , Peru

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La Libertad, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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San Isidro, , Peru

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Gdynia, , Poland

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Lodz, , Poland

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Szczecin, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Floreşti, , Romania

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Goyang-si, , South Korea

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Seongnam-si, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Suwon, , South Korea

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Córdoba, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Terrassa(Barcelona), , Spain

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Vigo, , Spain

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Adana, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Countries

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United States Austria Belgium Brazil Bulgaria Canada China Denmark Finland France Germany Hungary Italy Japan Peru Poland Romania South Korea Spain Turkey (Türkiye)

References

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Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

Reference Type DERIVED
PMID: 37185961 (View on PubMed)

Other Identifiers

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2017-004632-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D081RC00001

Identifier Type: -

Identifier Source: org_study_id

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