Does Cediranib With Paclitaxel, or Cediranib and Olaparib, Treat Advanced Endometrial Cancer Better Than Paclitaxel? — COPELIA  

Endometrial Neoplasms Clinical Trial

Official title: A 3-Arm Randomised Phase II Evaluation of Cediranib in Combination With Weekly Paclitaxel or Olaparib Versus Weekly Paclitaxel Chemotherapy for Advanced Endometrial Carcinoma or for Disease Relapse Within 18 Months of Adjuvant Carboplatin-paclitaxel Chemotherapy.

Status Active, not recruiting

Clinical Trial Summary

The COPELIA trial is evaluating two new tablet medications in endometrial cancer for the first time. It will include 129 women aged 16 years or older with advanced endometrial cancer whose cancer has worsened after their initial chemotherapy treatment. Participants will be allocated at random to one of three groups:

1. The first group (Arm 1) will receive a standard (routine) treatment for patients with endometrial cancer known as paclitaxel. This is a chemotherapy drug that is routinely used to treat patients with different cancers including ovarian, breast, lung and endometrial cancer. Paclitaxel works by stopping the growth of cancer cells.

2. The second group (Arm 2) will receive the standard paclitaxel treatment once a week in addition to a new drug called cediranib. Cediranib is a tablet medication and works by blocking new blood vessel formation. Cediranib has been tested in women with endometrial cancer before but not alongside chemotherapy treatment.

3. The third group (Arm 3) will receive two new tablet medications, cediranib and olaparib. Olaparib works by preventing cancer cells repairing DNA effectively. The use of olaparib and cediranib together has been shown to be effective in a common type of ovarian cancer but has not been evaluated as a treatment for endometrial cancer before.

The main objectives of the COPELIA trial are to work out:

1. Whether the two new treatments, cediranib-paclitaxel (Arm 2) and cediranib-olaparib (Arm 3) are more effective at controlling endometrial cancer than standard paclitaxel chemotherapy (Arm 1)

2. Whether the two new treatments cause more or fewer side-effects than standard chemotherapy

3. How each of these treatments impact on the daily life of women receiving the treatment by asking trial participants to regularly complete quality of life questionnaires

4. Whether we can learn how these treatments work in women with endometrial cancer by taking some additional blood tests for research.

Clinical Trial Description

COPELIA is a phase II, randomised, three-arm open-label trial which will recruit 129 women aged 16 years or older, with advanced endometrial cancer who require further treatment after their initial chemotherapy treatment. Potential participants will be recruited from the hospital setting.

Participants will be allocated to one of the following three trial arms on a 1:1:1 basis using centralised internet randomisation, stratified for prognostic factors:

Arm 1: (Control Arm): Paclitaxel 80 mg/m2 administered on days 1, 8 and 15 of a 28-day cycle for up to 6 cycles.

Arm 2: Cediranib 20 mg once daily for 28 days given with weekly paclitaxel 80 mg/m2 administered on days 1, 8 and 15 of a 28-day cycle for up to 6 cycles. Participants with stable disease, partial response or complete response at 6 months as determined by RECIST v1.1 will be eligible to continue treatment with single agent cediranib once daily until disease progression.

Arm 3: Cediranib 20 mg once daily with olaparib 300 mg twice daily, continuously on a 28 day cycle for up to 6 cycles. Participants with stable disease, partial response or complete response at 6 months as determined by RECIST v1.1 will be eligible to continue treatment with both olaparib and cediranib until disease progression.

Randomisation will be balanced for histological subtype and the number of chemotherapy regimens for metastatic disease.

Recruitment to the trial is expected to take 30 months. The total duration of the trial is expected to be 55 months. Participants will receive initial trial treatments for up to six months as long as they remain progression free. As mentioned above, participants in the experimental arms may continue treatment with cediranib/olaparib beyond the six months, and beyond the end of the trial, if they remain progression free. The trial will end once all participants have met at least one of the criteria: completed 12 months' follow-up (including treatment), withdrawn from follow-up, been lost to follow-up, experienced disease progression, or died. Participants consent for their medical notes to be reviewed at later dates if required to obtain data such as overall survival.

The trial has a multi-arm-multi-stage (MAMS) design. The appropriate sample size was calculated for this MAMS design, which allows one (or both) ineffective experimental arms to be dropped following a planned interim analysis after 60 participants have been assessed at three months. ;

Related Conditions & MeSH terms

• Carcinosarcoma
• Endometrial Neoplasms
• Mixed Tumor, Mullerian

• NCT number: NCT03570437
• Study type: Interventional
• Source: University of Manchester
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 17, 2018
• Completion date: June 30, 2023