Clinical trial NCT03737643: Durvalumab Treatment in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib Treatment in Advanced Ovarian Cancer Patients
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).
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Advanced Ovarian Cancer
Keywords: Advanced Ovarian Cancer
Ovarian neoplasms
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: European Network of Gynaecological Oncological Trial Groups (ENGOT)
name: GOG Foundation, Inc. (GOG Foundation)
name: Myriad Genetic Laboratories, Inc.
First posted: 2018-11-09
Enrollment: 1407
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Progression Free Survival (PFS) - in non-tBRCA HRD positive patients
timeFrame: Approximately 4 years
measure: Progression Free Survival (PFS) - in all non-tBRCA patients
timeFrame: Approximately 4 years
Secondary outcomes:
measure: Progression Free Survival (PFS) - in non-tBRCAm patients
timeFrame: Approximately 4 years
measure: Overall Survival (OS) - in non-tBRCA HRD positive patients and in all non-tBRCA patients
timeFrame: Approximately 7 years
measure: Second Progression (PFS2) - in non-tBRCAm patients
timeFrame: Approximately 7 years
measure: Health-related quality of life - in non-tBRCAm patients
timeFrame: Approximately 4 years
measure: Pathological Complete Response (pCR) - in non-tBRCAm patients
timeFrame: Approximately 4 years
measure: The pharmacokinetics (PK) and immunogenicity of durvalumab and olaparib as determined by peak concentration - in non-tBRCAm patients
timeFrame: Approximately 4 years
measure: Objective Response Rate (ORR) - in non-tBRCAm patients
timeFrame: Approximately 4 years
measure: Duration of response (DoR) - in non-tBRCAm patients
timeFrame: Approximately 4 years
measure: Time to first subsequent therapy (TFST) - in non-tBRCAm patients
timeFrame: Approximately 7 years
measure: Time to second subsequent therapy (TSST) - in non-tBRCAm patients
timeFrame: Approximately 7 years
measure: Time to discontinuation or death (TDT) - in non-tBRCAm patients
timeFrame: Approximately 4 years
measure: PFS - in tBRCAm patients
timeFrame: Approximately 4 years
measure: PFS2 - in tBRCAm patients
timeFrame: Approximately 7 years
measure: ORR - in tBRCAm patients
timeFrame: Approximately 4 years
measure: ORR pre-surgery in IDS group - in tBRCAm patients
timeFrame: Approximately 4 years
measure: Duration of response (DoR) - in tBRCAm patients
timeFrame: Approximately 4 years
measure: Time to first subsequent therapy (TFST) - in tBRCAm patients
timeFrame: Approximately 7 years
measure: Time to second subsequent therapy (TSST) - in tBRCAm patients
timeFrame: Approximately 7 years
measure: Time to discontinuation or death (TDT) - in tBRCAm patients
timeFrame: Approximately 4 years
measure: Health-related quality of life - in tBRCAm patients
timeFrame: Approximately 4 years
measure: Proportion of patients with pCR in patients undergoing IDS - in tBRCAm patients
timeFrame: Approximately 4 years
Other outcomes:
measure: Safety and tolerability of drugs by assessment of AEs/SAEs
timeFrame: Approximately 4 years
Locations:
city: Foothill Ranch
country: United States
facility: Research Site
state: California
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country: United States
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city: Limoges Cedex
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city: Nantes
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city: Paris Cedex 14
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city: Schweinfurt
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city: Zalaegerszeg
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city: Lecco
country: Italy
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city: Milano
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city: Milano
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city: Mirano
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city: Napoli
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city: Reggio Calabria
country: Italy
facility: Research Site
city: Reggio Emilia
country: Italy
facility: Research Site
city: Roma
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city: Torino
country: Italy
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city: Torino
country: Italy
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city: Fukuoka-shi
country: Japan
facility: Research Site
city: Kashiwa-shi
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Kurume-shi
country: Japan
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city: Kyoto-shi
country: Japan
facility: Research Site
city: Minato-ku
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Niigata-shi
country: Japan
facility: Research Site
city: Okayama-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Toyoake-shi
country: Japan
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Bellavista
country: Peru
facility: Research Site
city: La Libertad
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: San Isidro
country: Peru
facility: Research Site
city: Gdynia
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Floresti
country: Romania
facility: Research Site
city: Córdoba
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Terrassa(Barcelona)
country: Spain
facility: Research Site
city: Vigo
country: Spain
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
Study officials:
affiliation: European Network of Gynaecological Oncological Trial Groups (ENGOT)
name: Philipp Harter
role: PRINCIPAL_INVESTIGATOR
affiliation: GOG
name: Carol Aghajanian
role: PRINCIPAL_INVESTIGATOR
References: