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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03737643
Recruitment Status : Recruiting
First Posted : November 9, 2018
Last Update Posted : January 11, 2021
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 January 11, 2021
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
 (submitted: July 15, 2020)
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)
Original Primary Outcome Measures  ICMJE
 (submitted: November 8, 2018)
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
 (submitted: July 15, 2020)
  • Overall Survival (OS) - in non-tBRCAm 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
 (submitted: November 8, 2018)
  • 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
 (submitted: July 15, 2020)
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
 (submitted: November 8, 2018)
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 15, 2020)
1254
Original Estimated Enrollment  ICMJE
 (submitted: November 8, 2018)
1056
Estimated Study Completion Date  ICMJE November 14, 2025
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 150 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   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
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE
  • European Network of Gynaecological Oncological Trial Groups (ENGOT)
  • GOG Foundation, Inc. (GOG Foundation)
  • Myriad Genetic Laboratories, Inc.
Investigators  ICMJE
Principal Investigator: Philipp Harter European Network of Gynaecological Oncological Trial Groups (ENGOT)
Principal Investigator: Carol Aghajanian GOG
PRS Account AstraZeneca
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP