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

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ClinicalTrials.gov Identifier: NCT03737643

Recruitment Status : Active, not recruiting

First Posted : November 9, 2018

Last Update Posted : April 21, 2023

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborators:

European Network of Gynaecological Oncological Trial Groups (ENGOT)

GOG Foundation, Inc. (GOG Foundation)

Myriad Genetic Laboratories, Inc.

Information provided by (Responsible Party):

AstraZeneca

Tracking Information

First Submitted Date ^ICMJE

October 15, 2018

First Posted Date ^ICMJE

November 9, 2018

Last Update Posted Date

April 21, 2023

Actual Study Start Date ^ICMJE

January 4, 2019

Estimated Primary Completion Date

June 23, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Progression Free Survival (PFS) - in non-tBRCA HRD positive patients [ Time Frame: Approximately 4 years ]
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)
Progression Free Survival (PFS) - in all non-tBRCA patients [ Time Frame: Approximately 4 years ]
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)

Original Primary Outcome Measures ^ICMJE

Progression Free Survival (PFS) - in non-tBRCAm patients [ Time Frame: Approximately 6 years ]

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)

Change History

Current Secondary Outcome Measures ^ICMJE

Progression Free Survival (PFS) - in non-tBRCAm patients [ Time Frame: Approximately 4 years ]
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)
Overall Survival (OS) - in non-tBRCA HRD positive patients and in all non-tBRCA patients [ Time Frame: Approximately 7 years ]
Defined as the time from randomisation to death due to any cause
Second Progression (PFS2) - in non-tBRCAm patients [ Time Frame: Approximately 7 years ]
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)
Health-related quality of life - in non-tBRCAm patients [ Time Frame: Approximately 4 years ]
Change from baseline in the physical functioning subscale of the EORTC-QLQ-C30
Pathological Complete Response (pCR) - in non-tBRCAm patients [ Time Frame: Approximately 4 years ]
Defined as the proportion of patients with pCR in patients undergoing IDS
The pharmacokinetics (PK) and immunogenicity of durvalumab and olaparib as determined by peak concentration - in non-tBRCAm patients [ Time Frame: Approximately 4 years ]
Determination of durvalumab concentration in serum and olaparib concentration in plasma in a subset of patients
Objective Response Rate (ORR) - in non-tBRCAm patients [ Time Frame: Approximately 4 years ]
Defined as the number (%) of patients with at least one investigator-assessed visit response of CR or PR as per RECIST 1.1
Duration of response (DoR) - in non-tBRCAm patients [ Time Frame: Approximately 4 years ]
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
Time to first subsequent therapy (TFST) - in non-tBRCAm patients [ Time Frame: Approximately 7 years ]
Time elapsed from randomisation to first subsequent therapy or death
Time to second subsequent therapy (TSST) - in non-tBRCAm patients [ Time Frame: Approximately 7 years ]
Time elapsed from randomisation to second subsequent therapy or death
Time to discontinuation or death (TDT) - in non-tBRCAm patients [ Time Frame: Approximately 4 years ]
Time elapsed from randomisation to study treatment discontinuation or death
PFS - in tBRCAm patients [ Time Frame: Approximately 4 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
PFS2 - in tBRCAm patients [ Time Frame: Approximately 7 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
ORR - in tBRCAm patients [ Time Frame: Approximately 4 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
ORR pre-surgery in IDS group - in tBRCAm patients [ Time Frame: Approximately 4 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Duration of response (DoR) - in tBRCAm patients [ Time Frame: Approximately 4 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Time to first subsequent therapy (TFST) - in tBRCAm patients [ Time Frame: Approximately 7 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Time to second subsequent therapy (TSST) - in tBRCAm patients [ Time Frame: Approximately 7 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Time to discontinuation or death (TDT) - in tBRCAm patients [ Time Frame: Approximately 4 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Health-related quality of life - in tBRCAm patients [ Time Frame: Approximately 4 years ]
Change from baseline in the physical functioning subscale of the EORTC-QLQ-C30
Proportion of patients with pCR in patients undergoing IDS - in tBRCAm patients [ Time Frame: Approximately 4 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients

Original Secondary Outcome Measures ^ICMJE

Overall Survival (OS) - in non-tBRCAm patients [ Time Frame: Approximately 6 years ]
Defined as the time from randomisation to death due to any cause
Second Progression (PFS2) - in non-tBRCAm patients [ Time Frame: Approximately 6 years ]
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)
Health-related quality of life - in non-tBRCAm patients [ Time Frame: Approximately 3 years ]
Change from baseline in the physical functioning subscale of the EORTC-QLQ-C30
pathological Complete Response (pCR) - in non-tBRCAm patients [ Time Frame: Approximately 3 months after randomisation ]
Defined as the proportion of patients with pCR in patients undergoing IDS
The pharmacokinetics (PK) and immunogenicity of durvalumab and olaparib as determined by peak concentration - in non-tBRCAm patients [ Time Frame: Approximately 18 months ]
Determination of durvalumab concentration in serum and olaparib concentration in plasma in a subset of patients
Objective Response Rate (ORR) - in non-tBRCAm patients [ Time Frame: Approximately 6 years ]
Defined as the number (%) of patients with at least one investigator-assessed visit response of CR or PR as per RECIST 1.1
Duration of response (DoR) - in non-tBRCAm patients [ Time Frame: Approximately 6 years ]
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
Time to first subsequent therapy (TFST) - in non-tBRCAm patients [ Time Frame: Approximately 6 years ]
Time elapsed from randomisation to first subsequent therapy or death
Time to second subsequent therapy (TSST) - in non-tBRCAm patients [ Time Frame: Approximately 6 years ]
Time elapsed from randomisation to second subsequent therapy or death
Time to discontinuation or death (TDT) - in non-tBRCAm patients [ Time Frame: Approximately 30 months ]
Time elapsed from randomisation to study treatment discontinuation or death
PFS - in tBRCAm patients [ Time Frame: Approximately 6 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
PFS2 - in tBRCAm patients [ Time Frame: Approximately 6 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
ORR - in tBRCAm patients [ Time Frame: Approximately 6 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
ORR pre-surgery in IDS group - in tBRCAm patients [ Time Frame: Approximately 6 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
duration of response (DoR) - in tBRCAm patients [ Time Frame: Approximately 6 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Time to first subsequent therapy (TFST) - in tBRCAm patients [ Time Frame: Approximately 6 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Time to second subsequent therapy (TSST) - in tBRCAm patients [ Time Frame: Approximately 6 years ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Time to discontinuation or death (TDT) - in tBRCAm patients [ Time Frame: Approximately 30 months ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Health-related quality of life - in tBRCAm patients [ Time Frame: Approximately 3 years ]
Change from baseline in the physical functioning subscale of the EORTC-QLQ-C30
Proportion of patients with pCR in patients undergoing IDS - in tBRCAm patients [ Time Frame: Approximately 3 months after cohort allocation ]
To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients

Current Other Pre-specified Outcome Measures

Safety and tolerability of drugs by assessment of AEs/SAEs [ Time Frame: Approximately 4 years ]

Graded according to the National Cancer Institute (NCI CTCAE)

Original Other Pre-specified Outcome Measures

Safety and tolerability of drugs by assessment of AEs/SAEs [ Time Frame: Approximately 6 years ]

Graded according to the National Cancer Institute (NCI CTCAE)

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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).

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.

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
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

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition ^ICMJE

Advanced Ovarian Cancer

Intervention ^ICMJE

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: Placebo olaparib
Placebo tablets to match olaparib
Drug: Durvalumab placebo
Matching placebo for intravenous infusion
Drug: Carboplatin+Paclitaxel
Standard of care chemotherapy

Study Arms ^ICMJE

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).
Interventions:
- Drug: Bevacizumab
- Drug: Placebo olaparib
- Drug: Durvalumab placebo
- Drug: Carboplatin+Paclitaxel
Experimental: Arm 2
Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib placebo.
Interventions:
- Drug: Bevacizumab
- Drug: Durvalumab
- Drug: Placebo olaparib
- Drug: Carboplatin+Paclitaxel
Experimental: Arm 3
Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib.
Interventions:
- Drug: Bevacizumab
- Drug: Durvalumab
- Drug: Olaparib
- Drug: Carboplatin+Paclitaxel
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.
Interventions:
- Drug: Bevacizumab
- Drug: Durvalumab
- Drug: Olaparib
- Drug: Carboplatin+Paclitaxel

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Active, not recruiting

Actual Enrollment ^ICMJE

1404

Original Estimated Enrollment ^ICMJE

1056

Estimated Study Completion Date ^ICMJE

May 25, 2028

Estimated Primary Completion Date

June 23, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender ^ICMJE

Sexes Eligible for Study:	Female
Gender Based Eligibility:	Yes
Gender Eligibility Description:	All female patients newly diagnosed with advanced ovarian cancer

Ages ^ICMJE

18 Years to 130 Years (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

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

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT03737643

Other Study ID Numbers ^ICMJE

D081RC00001
2017-004632-11 ( EudraCT Number )

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No
Product Manufactured in and Exported from the U.S.:	Yes

IPD Sharing Statement ^ICMJE

Plan to Share IPD:	Yes
Plan Description:	Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting Materials:	Study Protocol
Supporting Materials:	Statistical Analysis Plan (SAP)
Time Frame:	AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria:	When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL:	https://astrazenecagroup-dt.pharmacm.com/DT/Home