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

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: NCT04269200
Recruitment Status : Recruiting
First Posted : February 13, 2020
Last Update Posted : November 23, 2020
Sponsor:
Collaborators:
The Gynecologic Oncology Group (GOG) Foundation Inc
The European Network for Gynaecological Oncological Trial groups (ENGOT)
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Endometrial Neoplasms Drug: olaparib Biological: durvalumab Drug: durvalumab placebo Drug: olaparib placebo Drug: Carboplatin Drug: Paclitaxel Phase 3

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 699 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: double-blind, placebo-controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : May 21, 2020
Estimated Primary Completion Date : September 26, 2023
Estimated Study Completion Date : March 5, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Arm A (control)
Platinum-based chemotherapy and durvalumab placebo followed by maintenance durvalumab placebo and olaparib placebo (tablets).
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

Experimental: Arm B (durvalumab+placebo)
Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib placebo
Biological: durvalumab
Durvalumab by intravenous infusion

Drug: olaparib placebo
Placebo tablets to match olaparib

Drug: Carboplatin
Standard of care chemotherapy

Drug: Paclitaxel
Standard of care chemotherapy

Experimental: Arm C (durvalumab+olaparib)
Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib.
Drug: olaparib
Olaparib tablets

Biological: durvalumab
Durvalumab by intravenous infusion

Drug: Carboplatin
Standard of care chemotherapy

Drug: Paclitaxel
Standard of care chemotherapy




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to 6 years ]
    Defined as the time from randomisation to death due to any cause

  2. 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

  3. 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.

  4. 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

  5. Time to first subsequent therapy (TFST) [ Time Frame: Up to 6 years ]
    Time elapsed from randomisation to first subsequent therapy or death

  6. Time to second subsequent therapy (TSST) [ Time Frame: Up to 6 years ]
    Time elapsed from randomisation to second subsequent therapy or death

  7. Time to discontinuation or death (TDT) [ Time Frame: Up to 6 years ]
    Time elapsed from randomisation to study treatment discontinuation or death

  8. The pharmacokinetics (PK) of durvalumab will be determined after steady state doses [ Time Frame: Up to 4 years ]
    Determination of durvalumab concentration in serum

  9. 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)

  10. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 150 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Female subjects only
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04269200


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
Show Show 189 study locations
Sponsors and Collaborators
AstraZeneca
The Gynecologic Oncology Group (GOG) Foundation Inc
The European Network for Gynaecological Oncological Trial groups (ENGOT)
Investigators
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Principal Investigator: Shannon N. Westin, MD, MPH, FACOG The University of Texas MD Anderson Cancer Center
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04269200    
Other Study ID Numbers: 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 )
First Posted: February 13, 2020    Key Record Dates
Last Update Posted: November 23, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
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
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Cancer of Endometrium
Cancer of the Endometrium
Carcinoma of Endometrium
Endometrial Cancer
Endometrial Carcinoma
Endometrium Cancer
Neoplasms, Endometrial
Additional relevant MeSH terms:
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Endometrial Neoplasms
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Paclitaxel
Carboplatin
Durvalumab
Olaparib
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immunologic Factors
Physiological Effects of Drugs
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors