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

Overview

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.

Full Title of Study: “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)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: June 5, 2023

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

Interventions

  • 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

Arms, Groups and Cohorts

  • Active Comparator: Arm A (control)
    • Platinum-based chemotherapy and durvalumab placebo followed by maintenance durvalumab placebo and olaparib placebo (tablets).
  • Experimental: Arm B (durvalumab+placebo)
    • Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib placebo
  • Experimental: Arm C (durvalumab+olaparib)
    • Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib.

Clinical Trial Outcome Measures

Primary Measures

  • 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 Measures

  • 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

Participating in This Clinical Trial

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.

Gender Eligibility: Female

Female subjects only

Minimum Age: 18 Years

Maximum Age: 150 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • AstraZeneca
  • Collaborator
    • The Gynecologic Oncology Group (GOG) Foundation Inc
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Shannon N. Westin, MD, MPH, FACOG, Principal Investigator, The University of Texas MD Anderson Cancer Center
  • Overall Contact(s)
    • AstraZeneca Clinical Study Information Center, 1-877-240-9479, information.center@astrazeneca.com

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