Clinical Trials /

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

NCT04269200

Description:

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.

Related Conditions:
  • Endometrial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Durvalumab With or Without Olaparib as Maintenance Therapy After First-Line Treatment of Advanced and Recurrent Endometrial Cancer
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: D9311C00001
  • SECONDARY ID: 2019-004112-60
  • SECONDARY ID: GOG-3041
  • SECONDARY ID: ENGOT-EN10
  • SECONDARY ID: D9311C00001
  • NCT ID: NCT04269200

Conditions

  • Endometrial Neoplasms

Interventions

DrugSynonymsArms
olaparibArm C (durvalumab+olaparib)
durvalumabArm B (durvalumab+placebo)
durvalumab placeboArm A (control)
olaparib placeboArm A (control)
CarboplatinArm A (control)
PaclitaxelArm A (control)

Purpose

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
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (control)Active ComparatorPlatinum-based chemotherapy and durvalumab placebo followed by maintenance durvalumab placebo and olaparib placebo (tablets).
  • durvalumab placebo
  • olaparib placebo
  • Carboplatin
  • Paclitaxel
Arm B (durvalumab+placebo)ExperimentalPlatinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib placebo
  • durvalumab
  • olaparib placebo
  • Carboplatin
  • Paclitaxel
Arm C (durvalumab+olaparib)ExperimentalPlatinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib.
  • olaparib
  • durvalumab
  • Carboplatin
  • Paclitaxel

Eligibility 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.
      
Maximum Eligible Age:150 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:upto to 4 years
Safety Issue:
Description: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

Measure:Overall Survival (OS)
Time Frame:Up to 6 years
Safety Issue:
Description:Defined as the time from randomisation to death due to any cause
Measure:Second Progression (PFS2)
Time Frame:Up to 6 years
Safety Issue:
Description:Defined as time from randomisation to the earliest of the progression event subsequent to first subsequent therapy or death
Measure:Objective Response Rate (ORR)
Time Frame:Up to 4 years
Safety Issue:
Description: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.
Measure:Duration of response (DoR)
Time Frame:Up to 4 years
Safety Issue:
Description: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
Measure:Time to first subsequent therapy (TFST)
Time Frame:Up to 6 years
Safety Issue:
Description:Time elapsed from randomisation to first subsequent therapy or death
Measure:Time to second subsequent therapy (TSST)
Time Frame:Up to 6 years
Safety Issue:
Description:Time elapsed from randomisation to second subsequent therapy or death
Measure:Time to discontinuation or death (TDT)
Time Frame:Up to 6 years
Safety Issue:
Description:Time elapsed from randomisation to study treatment discontinuation or death
Measure:The pharmacokinetics (PK) of durvalumab will be determined after steady state doses
Time Frame:Up to 4 years
Safety Issue:
Description:Determination of durvalumab concentration in serum
Measure:Safety and tolerability of drugs by assessment of AEs/SAEs
Time Frame:Up to 6 years
Safety Issue:
Description:Graded according to the National Cancer Institute (NCI CTCAE)
Measure:The immunogenicity of durvalumab as determined by concentration of Anti-drug antibodies (ADA) to durvalumab
Time Frame:Up to 4 years
Safety Issue:
Description:Determination concentration of Anti-drug antibodies (ADA) to durvalumab in serum

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Cancer of Endometrium
  • Cancer of the Endometrium
  • Carcinoma of Endometrium
  • Endometrial Cancer
  • Endometrial Carcinoma
  • Endometrium Cancer
  • Neoplasms, Endometrial

Last Updated

June 10, 2020