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.
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
Interventions
Drug | Synonyms | Arms |
---|
olaparib | | Arm C (durvalumab+olaparib) |
durvalumab | | Arm B (durvalumab+placebo) |
durvalumab placebo | | Arm A (control) |
olaparib placebo | | Arm A (control) |
Carboplatin | | Arm A (control) |
Paclitaxel | | Arm 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
Name | Type | Description | Interventions |
---|
Arm A (control) | Active Comparator | Platinum-based chemotherapy and durvalumab placebo followed by maintenance durvalumab placebo and olaparib placebo (tablets). | - durvalumab placebo
- olaparib placebo
- Carboplatin
- Paclitaxel
|
Arm B (durvalumab+placebo) | Experimental | Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib placebo | - durvalumab
- olaparib placebo
- Carboplatin
- Paclitaxel
|
Arm C (durvalumab+olaparib) | Experimental | Platinum-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
August 5, 2021