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

Advanced Ovarian Cancer Clinical Trial

— DUO-O  

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).

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03737643
• Other study ID #: D081RC00001
• Secondary ID: 2017-004632-11
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 4, 2019
• Est. completion date: May 25, 2028

Study information

• Verified date: January 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1407
• Est. completion date: May 25, 2028
• Est. primary completion date: September 18, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 130 Years

Eligibility

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

Related Conditions & MeSH terms

• Advanced Ovarian Cancer
• Carcinoma, Ovarian Epithelial
• Ovarian Neoplasms

Intervention

Drug:
• Bevacizumab
Bevacizumab by intravenous infusion. In tBRCAm cohort bevacizumab is optional according to local practice.
• Durvalumab
Durvalumab by intravenous infusion
• Olaparib
Olaparib tablets
• Placebo olaparib
Placebo tablets to match olaparib
• Durvalumab placebo
Matching placebo for intravenous infusion
• Carboplatin+Paclitaxel
Standard of care chemotherapy

Locations

Country	Name	City	State
Austria	Research Site	Graz
Austria	Research Site	Innsbruck
Austria	Research Site	Linz
Austria	Research Site	Wien
Belgium	Research Site	Aalst
Belgium	Research Site	Leuven
Belgium	Research Site	Namur
Belgium	Research Site	Oostende
Belgium	Research Site	Sint-Niklaas
Brazil	Research Site	Barretos
Brazil	Research Site	Florianópolis
Brazil	Research Site	Fortaleza
Brazil	Research Site	Londrina
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Bulgaria	Research Site	Burgas
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Varna
Canada	Research Site	Barrie	Ontario
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Rimouski	Quebec
Canada	Research Site	Sudbury	Ontario
Canada	Research Site	Toronto	Ontario
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Bengbu
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Dalian
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Hefei
China	Research Site	Jinhua
China	Research Site	Kunming
China	Research Site	Lanzhou
China	Research Site	Luzhou
China	Research Site	Nan Chong
China	Research Site	Nanjing
China	Research Site	Nanning
China	Research Site	Nantong
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Zhengzhou
China	Research Site	Zhengzhou
China	Research Site	Zhuhai
Denmark	Research Site	Aalborg
Denmark	Research Site	Aarhus N
Denmark	Research Site	Odense C
Denmark	Research Site	Roskilde
Denmark	Research Site	Vejle
Finland	Research Site	Kuopio
Finland	Research Site	Oulu
Finland	Research Site	Turku
France	Research Site	Besançon
France	Research Site	Bordeaux
France	Research Site	Limoges Cedex
France	Research Site	Lyon Cedex 08
France	Research Site	Marseille
France	Research Site	Nantes
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Paris Cedex 14
France	Research Site	Saint Herblain Cedex
France	Research Site	Vandoeuvre les Nancy
Germany	Research Site	Bad Homburg
Germany	Research Site	Berlin
Germany	Research Site	Bielefeld
Germany	Research Site	Bonn
Germany	Research Site	Brandenburg
Germany	Research Site	Dresden
Germany	Research Site	Düsseldorf
Germany	Research Site	Essen
Germany	Research Site	Essen
Germany	Research Site	Esslingen am Neckar
Germany	Research Site	Frankfurt
Germany	Research Site	Freiburg
Germany	Research Site	Fürth
Germany	Research Site	Greifswald
Germany	Research Site	Gütersloh
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Hannover
Germany	Research Site	Jena
Germany	Research Site	Karlsruhe
Germany	Research Site	Karlsruhe
Germany	Research Site	Kassel
Germany	Research Site	Kiel
Germany	Research Site	Köln
Germany	Research Site	Leipzig
Germany	Research Site	Lübeck
Germany	Research Site	Ludwigsburg
Germany	Research Site	Mainz
Germany	Research Site	Mannheim
Germany	Research Site	München
Germany	Research Site	Offenbach am Main
Germany	Research Site	Oldenburg
Germany	Research Site	Rosenheim
Germany	Research Site	Rostock
Germany	Research Site	Saalfeld
Germany	Research Site	Schweinfurt
Germany	Research Site	Tübingen
Germany	Research Site	Ulm
Germany	Research Site	Worms
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Gyor
Hungary	Research Site	Kaposvár
Hungary	Research Site	Szeged
Hungary	Research Site	Zalaegerszeg
Italy	Research Site	Brescia
Italy	Research Site	Lecce
Italy	Research Site	Lecco
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Mirano
Italy	Research Site	Napoli
Italy	Research Site	Reggio Calabria
Italy	Research Site	Reggio Emilia
Italy	Research Site	Roma
Italy	Research Site	Torino
Italy	Research Site	Torino
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Kashiwa-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Kurume-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Minato-ku
Japan	Research Site	Nagoya-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Sunto-gun
Japan	Research Site	Toyoake-shi
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon-si
Peru	Research Site	Bellavista
Peru	Research Site	La Libertad
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	San Isidro
Poland	Research Site	Gdynia
Poland	Research Site	Lódz
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Romania	Research Site	Floresti
Spain	Research Site	Córdoba
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Terrassa(Barcelona)
Spain	Research Site	Vigo
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
United States	Research Site	Albany	New York
United States	Research Site	Augusta	Georgia
United States	Research Site	Cleveland	Ohio
United States	Research Site	Dayton	Ohio
United States	Research Site	Detroit	Michigan
United States	Research Site	Durham	North Carolina
United States	Research Site	Foothill Ranch	California
United States	Research Site	Hilliard	Ohio
United States	Research Site	Hinsdale	Illinois
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Lancaster	Pennsylvania
United States	Research Site	Los Angeles	California
United States	Research Site	Middletown	New Jersey
United States	Research Site	Montvale	New Jersey
United States	Research Site	New York	New York
United States	Research Site	Orange	California
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Francisco	California
United States	Research Site	Springfield	Missouri
United States	Research Site	Tampa	Florida
United States	Research Site	Towson	Maryland
United States	Research Site	Tulsa	Oklahoma
United States	Research Site	Uniondale	New York

Sponsors (4)

Lead Sponsor	Collaborator
AstraZeneca	European Network of Gynaecological Oncological Trial Groups (ENGOT), GOG Foundation, Inc. (GOG Foundation), Myriad Genetic Laboratories, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Denmark,  Finland,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Peru,  Poland,  Romania,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety and tolerability of drugs by assessment of AEs/SAEs	Graded according to the National Cancer Institute (NCI CTCAE)	Approximately 4 years
Primary	Progression Free Survival (PFS) - in non-tBRCA HRD positive patients	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)	Approximately 4 years
Primary	Progression Free Survival (PFS) - in all non-tBRCA patients	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)	Approximately 4 years
Secondary	Progression Free Survival (PFS) - in non-tBRCAm patients	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)	Approximately 4 years
Secondary	Overall Survival (OS) - in non-tBRCA HRD positive patients and in all non-tBRCA patients	Defined as the time from randomisation to death due to any cause	Approximately 7 years
Secondary	Second Progression (PFS2) - in non-tBRCAm patients	Defined as time from randomisation to second progression by investigator assessment of radiological progression, symptomatic progression or death (by any cause in the absence of progression)	Approximately 7 years
Secondary	Health-related quality of life - in non-tBRCAm patients	Change from baseline in the physical functioning subscale of the EORTC-QLQ-C30	Approximately 4 years
Secondary	Pathological Complete Response (pCR) - in non-tBRCAm patients	Defined as the proportion of patients with pCR in patients undergoing IDS	Approximately 4 years
Secondary	The pharmacokinetics (PK) and immunogenicity of durvalumab and olaparib as determined by peak concentration - in non-tBRCAm patients	Determination of durvalumab concentration in serum and olaparib concentration in plasma in a subset of patients	Approximately 4 years
Secondary	Objective Response Rate (ORR) - in non-tBRCAm patients	Defined as the number (%) of patients with at least one investigator-assessed visit response of CR or PR as per RECIST 1.1	Approximately 4 years
Secondary	Duration of response (DoR) - in non-tBRCAm patients	Defined as the time form the date of first documented response (CR/PR) until the first progression or death in the absence of disease progression	Approximately 4 years
Secondary	Time to first subsequent therapy (TFST) - in non-tBRCAm patients	Time elapsed from randomisation to first subsequent therapy or death	Approximately 7 years
Secondary	Time to second subsequent therapy (TSST) - in non-tBRCAm patients	Time elapsed from randomisation to second subsequent therapy or death	Approximately 7 years
Secondary	Time to discontinuation or death (TDT) - in non-tBRCAm patients	Time elapsed from randomisation to study treatment discontinuation or death	Approximately 4 years
Secondary	PFS - in tBRCAm patients	To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients	Approximately 4 years
Secondary	PFS2 - in tBRCAm patients	To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients	Approximately 7 years
Secondary	ORR - in tBRCAm patients	To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients	Approximately 4 years
Secondary	ORR pre-surgery in IDS group - in tBRCAm patients	To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients	Approximately 4 years
Secondary	Duration of response (DoR) - in tBRCAm patients	To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients	Approximately 4 years
Secondary	Time to first subsequent therapy (TFST) - in tBRCAm patients	To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients	Approximately 7 years
Secondary	Time to second subsequent therapy (TSST) - in tBRCAm patients	To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients	Approximately 7 years
Secondary	Time to discontinuation or death (TDT) - in tBRCAm patients	To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients	Approximately 4 years
Secondary	Health-related quality of life - in tBRCAm patients	Change from baseline in the physical functioning subscale of the EORTC-QLQ-C30	Approximately 4 years
Secondary	Proportion of patients with pCR in patients undergoing IDS - in tBRCAm patients	To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients	Approximately 4 years