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Durvalumab With or Without Olaparib as Maintenance Therapy After First-Line Treatment of Advanced and Recurrent Endometrial Cancer (DUO-E)

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ClinicalTrials.gov Identifier: NCT04269200
Recruitment Status : Recruiting
First Posted : February 13, 2020
Last Update Posted : March 25, 2021
Sponsor:
Collaborators:
The Gynecologic Oncology Group (GOG) Foundation Inc
The European Network for Gynaecological Oncological Trial groups (ENGOT)
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE February 10, 2020
First Posted Date  ICMJE February 13, 2020
Last Update Posted Date March 25, 2021
Actual Study Start Date  ICMJE May 21, 2020
Estimated Primary Completion Date September 26, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 12, 2020)
Progression Free Survival (PFS) [ Time Frame: upto to 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 Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2020)
  • Overall Survival (OS) [ Time Frame: Up to 6 years ]
    Defined as the time from randomisation to death due to any cause
  • Second Progression (PFS2) [ Time Frame: Up to 6 years ]
    Defined as time from randomisation to the earliest of the progression event subsequent to first subsequent therapy or death
  • Objective Response Rate (ORR) [ Time Frame: Up to 4 years ]
    Objective response rate is defined as the proportion of patients with measurable disease at baseline who have confirmed complete response (CR) or partial response (PR) as determined by the Investigator at local site.
  • Duration of response (DoR) [ Time Frame: Up to 4 years ]
    Defined as the time from the date of first documented confirmed response (CR/PR) until the first progression or death in the absence of disease progression
  • Time to first subsequent therapy (TFST) [ Time Frame: Up to 6 years ]
    Time elapsed from randomisation to first subsequent therapy or death
  • Time to second subsequent therapy (TSST) [ Time Frame: Up to 6 years ]
    Time elapsed from randomisation to second subsequent therapy or death
  • Time to discontinuation or death (TDT) [ Time Frame: Up to 6 years ]
    Time elapsed from randomisation to study treatment discontinuation or death
  • The pharmacokinetics (PK) of durvalumab will be determined after steady state doses [ Time Frame: Up to 4 years ]
    Determination of durvalumab concentration in serum
  • Safety and tolerability of drugs by assessment of AEs/SAEs [ Time Frame: Up to 6 years ]
    Graded according to the National Cancer Institute (NCI CTCAE)
  • The immunogenicity of durvalumab as determined by concentration of Anti-drug antibodies (ADA) to durvalumab [ Time Frame: Up to 4 years ]
    Determination concentration of Anti-drug antibodies (ADA) to durvalumab in serum
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Durvalumab With or Without Olaparib as Maintenance Therapy After First-Line Treatment of Advanced and Recurrent Endometrial Cancer
Official Title  ICMJE A Randomised, Multicentre, Double-blind, Placebo-controlled, Phase III Study of First-line Carboplatin and Paclitaxel in Combination With Durvalumab, Followed by Maintenance Durvalumab With or Without Olaparib in Patients With Newly Diagnosed Advanced or Recurrent Endometrial Cancer (DUO-E)
Brief Summary A study to assess the efficacy and safety of durvalumab in combination with platinum-based chemotherapy (paclitaxel + carboplatin) followed by maintenance durvalumab with or without olaparib for patients with newly diagnosed advanced or recurrent endometrial cancer.
Detailed Description

This Phase III study will assess the efficacy and safety of durvalumab in combination with platinum-based chemotherapy (paclitaxel + carboplatin) followed by maintenance durvalumab with or without olaparib for patients with newly diagnosed advanced or recurrent endometrial cancer.

Target patient population: Adult female patients with histologically confirmed diagnosis of epithelial endometrial carcinoma (excluding sarcomas): newly diagnosed Stage III, newly diagnosed Stage IV, or recurrent endometrial cancer

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
double-blind, placebo-controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Endometrial Neoplasms
Intervention  ICMJE
  • Drug: olaparib
    Olaparib tablets
  • Biological: durvalumab
    Durvalumab by intravenous infusion
  • Drug: durvalumab placebo
    Matching placebo for intravenous infusion
  • Drug: olaparib placebo
    Placebo tablets to match olaparib
  • Drug: Carboplatin
    Standard of care chemotherapy
  • Drug: Paclitaxel
    Standard of care chemotherapy
Study Arms  ICMJE
  • Active Comparator: Arm A (control)
    Platinum-based chemotherapy and durvalumab placebo followed by maintenance durvalumab placebo and olaparib placebo (tablets).
    Interventions:
    • Drug: durvalumab placebo
    • Drug: olaparib placebo
    • Drug: Carboplatin
    • Drug: Paclitaxel
  • Experimental: Arm B (durvalumab+placebo)
    Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib placebo
    Interventions:
    • Biological: durvalumab
    • Drug: olaparib placebo
    • Drug: Carboplatin
    • Drug: Paclitaxel
  • Experimental: Arm C (durvalumab+olaparib)
    Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib.
    Interventions:
    • Drug: olaparib
    • Biological: durvalumab
    • Drug: Carboplatin
    • Drug: 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: February 12, 2020)
699
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 5, 2025
Estimated Primary Completion Date September 26, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥18 years at the time of screening and female.
  • Histologically confirmed diagnosis of epithelial endometrial carcinoma. All histologies, including carcinosarcomas, will be allowed. Sarcomas will not be allowed.
  • Patient must have endometrial cancer in one of the following categories:

    1. Newly diagnosed Stage III disease (measurable disease per RECIST 1.1 following surgery or diagnostic biopsy),
    2. Newly diagnosed Stage IV disease (with or without disease following surgery or diagnostic biopsy)
    3. Recurrence of disease where the potential for cure by surgery alone or in combination is poor.
  • Naïve to first line systemic anti-cancer treatment. For patients with recurrent disease only, prior chemotherapy is allowed only if it was administered in the adjuvant setting and there is at least 12 months from date of last dose of chemotherapy administered to date of subsequent relapse
  • FPPE tumor sample must be available for MMR evaluation.
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study treatment.

Exclusion Criteria:

  • History of leptomeningeal carcinomatosis.
  • Brain metastases or spinal cord compression.
  • Prior treatment with PARP inhibitors.
  • Prior immune checkpoint inhibitors or prior treatment with an agent directed to a

stimulatory or co-inhibitor T-cell receptor other than anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Female subjects only
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 Australia,   Belgium,   Brazil,   Canada,   China,   Colombia,   Estonia,   Germany,   Greece,   Hong Kong,   Hungary,   India,   Israel,   Japan,   Korea, Republic of,   Lithuania,   Mexico,   Poland,   Russian Federation,   Singapore,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04269200
Other Study ID Numbers  ICMJE D9311C00001
2019-004112-60 ( EudraCT Number )
GOG-3041 ( Other Identifier: Gynecologic Oncology Group(GOG) Foundation Inc )
ENGOT-EN10 ( Other Identifier: The European Network for Gynaecological Oncological Trial groups )
D9311C00001 ( Other Identifier: AZ DCode )
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
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 deidentified 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
  • The Gynecologic Oncology Group (GOG) Foundation Inc
  • The European Network for Gynaecological Oncological Trial groups (ENGOT)
Investigators  ICMJE
Principal Investigator: Shannon N. Westin, MD, MPH, FACOG The University of Texas MD Anderson Cancer Center
PRS Account AstraZeneca
Verification Date March 2021

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