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

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Endometrial Neoplasms

Treatments: Drug: Carboplatin; Biological: durvalumab; Drug: olaparib placebo; Drug: durvalumab placebo; Drug: olaparib; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT04269200

D9311C00001 (Other Identifier)

2019-004112-60 (EudraCT Number)

ENGOT-EN10 (Other Identifier)

GOG-3041 (Other Identifier)

Details and patient eligibility

About

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 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

Enrollment: 805 patients

Sex: Female

Ages: 18 to 150 years old

Volunteers: No Healthy Volunteers

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 (measurable or non-measurable disease per RECIST 1.1) 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 systemic anti-cancer treatment is allowed only if it was administered in the adjuvant setting and there is at least 12 months from date of last dose of systemic anti-cancer treatment 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.
• Any prior exposure to immune-mediated therapy, including (but not limited to) other anti CTLA-4, anti-PD-1, anti-PD-L1, or anti-programmed-cell-death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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805 participants in 3 patient groups

Arm A (control)

Active Comparator group

Description:

Platinum-based chemotherapy and durvalumab placebo followed by maintenance durvalumab placebo and olaparib placebo (tablets).

Treatment:

Drug: Paclitaxel

Drug: durvalumab placebo

Drug: olaparib placebo

Drug: Carboplatin

Arm B (durvalumab+placebo)

Experimental group

Description:

Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib placebo

Treatment:

Drug: Paclitaxel

Drug: olaparib placebo

Biological: durvalumab

Drug: Carboplatin

Arm C (durvalumab+olaparib)

Experimental group

Description:

Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib.

Treatment:

Drug: Paclitaxel

Drug: olaparib

Biological: durvalumab

Drug: Carboplatin