COPELIA

The COPELIA trial is testing whether two new tablet medications delay progression of endometrial cancer more than chemotherapy alone.

Background

Over the last 20 years, there has been a 50% increase in the number of women in the UK developing endometrial cancer (cancer arising from the lining of the womb). For women with advanced disease, chemotherapy treatment is often recommended, but its benefits may be limited. New treatments are needed and so the COPELIA trial is testing whether two new tablet medications delay progression of endometrial cancer more than chemotherapy alone.

Recruitment

The COPELIA trial will recruit 129 adult women, with advanced endometrial cancer who require further treatment after initial chemotherapy.

Study design

Participants will be randomly allocated to one of three groups:

Group one will receive a routine chemotherapy treatment for patients with endometrial cancer known as paclitaxel. Paclitaxel works by stopping the growth of cancer cells. In this trial, paclitaxel is given via an hour-long infusion into a vein three times a month for six months.

Group two will receive paclitaxel treatment (as above) in addition to a new drug called cediranib. Cediranib is a tablet medication, taken once a day, that works by blocking new blood vessel formation. Cediranib has been tested in women with endometrial cancer, but not alongside chemotherapy treatment.

Group three will receive two new tablet medications, cediranib and olaparib. Cediranib is taken once a day and olaparib twice daily. Olaparib works by preventing cancer cells repairing DNA effectively. The use of olaparib and cediranib together has been shown to be effective in a type of ovarian cancer, but has not been tested as a treatment for endometrial cancer.

Patients will be recruited from cancer treatment centres.

Treatments will be for six months unless disease progresses. Patients may continue with cediranib and olaparib if they remain stable.

Results

The most common type of cancer of the womb is called endometrial cancer. This is a cancer that develops in the inside lining of the womb. Endometrial cancer causes bleeding, usually in women who have already completed their menopause. As a result, endometrial cancer is usually found at an early stage when it can be cured by surgery and sometimes chemotherapy and radiotherapy.

In a small proportion of patients, endometrial cancer can return and there are several different treatment options. In COPELIA, we compared the effectiveness and side effects of 3 different treatments in patients with recurrent endometrial cancer:

• Paclitaxel (also known as taxol), given for 3 out of 4 weeks.
• Weekly paclitaxel, given for 3 out of 4 weeks, with oral cediranib.
• Oral cediranib and oral olaparib.

Paclitaxel is a chemotherapy drug that has been used to treat endometrial cancer for many years. Cediranib is an oral drug that targets blood vessels inside cancers so that they are deprived of oxygen and nutrients; an anti-vascular drug. Olaparib is a drug that stops cells recovering from damage to DNA; a member of the PARP inhibitor family.

In COPELIA, 124 patients were randomly allocated to one of the three arms listed above. The main question was which treatment controlled the illness for at least 3 months. The results showed that the most effective treatment was the weekly paclitaxel and cediranib combination. It had a greater chance of shrinking the cancer than the other two treatments and kept the cancer under control in a larger number of patients than the other two arms. However, a greater number of patients, treated with paclitaxel and cediranib, had side effects from treatment. Significant side effects included diarrhoea, fatigue and raised blood pressure.

COPELIA has identified that weekly paclitaxel and cediranib is an effective treatment option in recurrent endometrial cancer. A larger randomised trial is needed to establish this combination as a standard of care.