Phase 1b/II Trial of Pembrolizumab Plus IMRT in Stage III/IV Carcinoma of Anus
Status:
Recruiting
Trial end date:
2022-11-30
Target enrollment:
Participant gender:
Summary
The CORINTH trial is for patients with more advanced (stage 3 and 4) anal cancer. The numbers
of patients with anal cancer is increasing and only 65% patients with this later stage anal
cancer have not had a recurrence 3 years after treatment. Anal cancer responds well to
chemo-radiation (CRT) and this would be the treatment used for standard clinical care. The
chemotherapy in CORINTH will be the same as standard of care (Mitomycin and 5FU or
capecitabine) and the radiotherapy (RT) will be delivered using a technique where the dose
intensity of RT can be modulated for different areas of the tumor (Intensity Modulated RT -
IMRT). Translational samples (tissue blocks and blood) will be collected at baseline with
further blood and tissue samples during and after treatment.
Pembrolizumab, a relatively new drug, is a monoclonal antibody that enhances the body's
immune response to cancer cells by acting on a receptor on the surface of T-cells called
Programmed Death -1 (PD-1). The CORINTH study aims to see whether pembrolizumab, can be added
safely to standard CRT. We will explore how safe the combination is and how well tolerated it
is for patients with stage 3 and 4 anal cancer. If it is tolerable more patients will be
treated to see if there is a similar or better clinical response.
The trial is designed in 3 groups of patients. All patients will receive eight infusions of
pembrolizumab at three weekly intervals. Each infusion lasts approximately 1 hour. The first
group will not get pembrolizumab until they have already had 4 weeks of CRT (Day 29). As long
as this is not found to cause too many extra side effects, the next group will have infusions
at the beginning of the third week of CRT. The final group (cohort 3) will start their
pembrolizumab with the first day of CRT i.e. Day 1.
Initially each group will have 6 patients. Provided each group of patients finds the
treatment tolerable and it is safe, more patients will be recruited into the group that
receives the pembrolizumab earliest during their CRT. This will add further credence to the
safety and tolerability of the combination and may provide a signal of how effective this
treatment might be in improving outcomes for patients with more advanced anal cancer.