CEBOC

• Research type

  Research Study

• Full title

  Evaluation of the safety of CEdiranib in the prevention of Bowel perforation in platinum-resistant Ovarian Cancer

• IRAS ID

  216211

• Contact name

  Gordon Jayson

• Contact email

  Gordon.jayson@christie.nhs.uk

• Sponsor organisation

  University of Manchester

• Eudract number

  2016-004618-93

• Clinicaltrials.gov Identifier

  U1111-1200-5948, WHO UT number:

• Duration of Study in the UK

  2 years, 0 months, 1 days

• Research summary

  Research Summary:

  In the UK, ovarian cancer is the fourth most common cause of female cancer death and the commonest cause of gynaecological cancer death accounting for 4,000 lives a year in the UK. The principal cause of death in ovarian cancer is malignant bowel obstruction. Because the disease causes multi-site obstruction of the bowel, surgery is seldom possible and there is a critical need to develop new treatments to stop development of bowel obstruction as effectively and safely as possible. CEBOC is the first trial that has been developed specifically to address the management of malignant bowel obstruction.

  CEBOC aims to take advantage of the additive effects of combining a VEGF inhibitor, cediranib, with an effective chemotherapeutic regimen, weekly paclitaxel. Subsequently, the patient can continue cediranib with the addition of an additional drug, olaparib at the point of progression. Olaparib is a PARP inhibitor which prevents cancer cells repairing DNA effectively and leads to the cells dying. Olaparib is already licensed for treatment of ovarian cancer in women with changes in their BRCA gene. This trial will allow participants, irrespective of their BRCA gene status, to receive olaparib in combination with cediranib because trial data suggests that the two drugs may be more effective when taken together.

  CEBOC will recruit 30 women aged 16 years or older with ovarian cancer, which has placed the patient at risk of developing bowel obstruction.

  The main objective of the trial is to determine the safety of combining cediranib with paclitaxel. Safety will be assessed by monitoring the frequency of two serious adverse events, bowel perforation and fistula. The trial will also summarise the side-effects of the treatments and how well the treatment works in terms of controlling the disease and preventing bowel obstruction.

  Summary of Results:

  One of the major problems caused by ovarian cancer is bowel obstruction (blockage) and it is important to prevent this complication arising as it is difficult to reverse. In CEBOC, we recruited patients whose ovarian cancer had become resistant to platinum-containing chemotherapy. We had developed a questionnaire to detect patients who were about to develop bowel obstruction and these patients were invited to participate in the trial.
  We planned to treat the patients with weekly paclitaxel, a standard chemotherapy option in this situation. However, we knew that drugs, which block blood vessel formation increase the effectiveness of chemotherapy when given with chemotherapy, yet they can also cause bowel damage if given to patients with bowel obstruction caused by cancer. In CEBOC we therefore wanted to test the safety of adding a drug that blocks blood vessel formation, called cediranib, to weekly paclitaxel.
  We did not manage to treat the planned number of patients for the trial as the weekly paclitaxel was less effective than we had hoped. So, further studies are needed with this combination. However, in those patients who did receive weekly paclitaxel and cediranib, the combination was safe and patients did not incur bowel damage. The regimen also appeared to be active but because of the smaller numbers of patients in the study we would recommend further evaluation of this regimen. The summary of the trial can be found at https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fpubmed.ncbi.nlm.nih.gov%252F38724236%252F%2FNBTI%2F5QC7AQ%2FAQ%2Fd2cab243-759e-4c32-9e8c-d37d67bdcd31%2F1%2FZmipsiiuso&data=05%7C02%7Cliverpoolcentral.rec%40hra.nhs.uk%7C9fd8d2086f1347d2336608dd3fa38200%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638736693667925890%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=5bIigi2HyGR1F8oDLIcg5%2FBclZSyqY0B7VhvqNVk%2B0s%3D&reserved=0

• REC name

  North West - Liverpool Central Research Ethics Committee

• REC reference

  17/NW/0623

• Date of REC Opinion

  12 Dec 2017

• REC opinion

  Further Information Favourable Opinion