CO.23

Protocol Title

A phase III randomised study of BBI608 and best supportive care versus placebo and best supportive care in patients with pre-treated advanced colorectal carcinoma.

Conference Presentation Reference

1. Jonker DJ, Nott L, Yoshino T, Gill S, Shapiro J, Ohtsu A, Zalcberg J, Vickers MM, Wei A, Gao Y, Tebbutt N, Markman B, Esaki T, Koski S, Hitron M, Magoski NM, Simes J, Li C, Tu D, O’Callaghan CJ. A randomized phase III study of napabucasin [BBI608] vs placebo in patients with pretreated advanced colorectal cancer: the CCTG/AGITG CO.23 trial. European Society for Medical Oncology 41st Congress; 7–11 Oct 2016 2016; Copenhagen.
2. Jonker DJ, Nott LM, Yoshino T, Li C, Gill S, Shapiro JD, Ohtsu A, Zalcberg JR, Vickers MM, Simes J, Wei AC, Mittmann N, Magoski NM, Murray Y, Tsobanis E, Tu D, Kerstein D, O’Callaghan CJ. NCIC CTG and AGITG CO.23 trial: a phase III randomized study of BBI608 plus best supportive care versus placebo plus best supportive care in patients with pretreated advanced colorectal carcinoma. American Society of Clinical Oncology 50th Annual Meeting; 30 May–3 Jun 2014; Chicago.

Aim

The CO.23 study evaluates the effect on overall survival and progression free survival of a drug called BBI6008(a cancer stem cell inhibitor) along with best supportive care compared to placebo with best supportive care for the treatment of refractory advanced colorectal cancer.

Background

In Australia, colorectal cancer (large bowel) cancer is the second highest cause of cancer related death in the country. In 2017, estimated 16,682 new cases of colorectal cancer will be diagnosed.

Cancer stem cells are a sub-population of cancer cells that have self-renewal capability, are highly malignant and are considered to be fundamentally responsible for malignant growth, recurrence, drug-resistance and metastasis. In addition, cancer stem cells are highly resistant to chemotherapies and current targeted agents.

Previous studies have suggested that the development of cancer stem cell inhibitors represent a new strategy in colorectal cancer treatment. BBI608 is a small molecule that blocks self-renewal of, and induces cell death in cancer stem cells in colorectal cancer and other types of cancer.

The CO.23 trial investigated the effectiveness of the cancer stem cell inhibitor (BBI608) on overall survival in patients by treating patients with advanced colorectal cancer that have exhausted all other treatment options.

The CO.23 interim analysis data was reviewed by the Canadian Cancer Trials Group Data Safety Monitoring Committee which concluded that, as per protocol criteria, there was no evidence of efficacy with the experimental arm. The study was closed in May 2014. Follow-up continued for survival status, and a final analysis occurred in late 2015. Results of analysis were presented as an abstract at ESMO Oncology Conference in October 2016. There was no difference in overall survival or progression free survival or disease control rate between the two groups. Participants of the trial are no longer followed up for the purpose of this trial.

Clinical Trial Design

The CO.23 study is an international multi-centre, prospective, double-blind, randomized phase III trial. The trial will have eligible patients randomised into two groups. One group will receive BB160, a cancer stem cell inhibitor drug and best supportive care. The other patient group will receive placebo tablets in addition to best supportive care (defined as measures designed to ease symptoms and improve quality of life as much as possible).

Treatment in both groups will be taken as tablets twice per day in continuous 28-day cycles. Duration of the treatment will be determined by the investigator as long as patients do not experience any adverse effects.

There will be assessment of patient status every 2 to 4 weeks while on treatment and then every 8 weeks to evaluate how they are responding to treatment.

Principal Investigator

Dr Louise Nott
A/Prof Jeremy Shapiro

Funding

Canadian Cancer Trials Group (CCTG)