A Phase 1 interventional study of Pembrolizumab in Anal Cancer Stage III A and Anal Cancer Stage III B, sponsored by Cardiff University. Active, not recruiting at 11 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-08-05.
Sponsored by Cardiff University · Phase 1, Interventional, and Treatment
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.
CORINTH is a multi center trial with a single arm. Patients will be recruited into 3 successive cohorts followed by an expansion of the final cohort. For each cohort the first dose of Pembrolizumab will be given at an earlier time point during the chemo-radiation (CRT).
Pembrolizumab will be given as an IV infusion every 21 days, and a total of 8 infusions per patient at 200mg per infusion. The first dose of pembrolizumab will be given at the following times:
COHORT 1: beginning at Week 5 day 1 of CRT schedule COHORT 2: beginning at Week 3 day 1 of CRT schedule COHORT 3: beginning at Week 1 day 1 of CRT schedule** Cohort 2 will be dependent on a Safety Review Committee (SRC) recommendation. If the SRC are concerned about toxicity in Cohort 1 but not sufficiently to stop the study, they are able to recommend that Cohort 2 can change to commence pembrolizumab at week 4. If the SRC are concerned about toxicity in Cohort 2 but not sufficiently to stop the study, they are able to recommend that Cohort 3 can change to commence pembrolizumab at week 2.
Potential participants will be under the care of a consultant who specializes in the treatment of anal cancer and the patient will have been identified as requiring CRT treatment for their anal cancer. They will be assessed for eligibility before being consented and allocated to the current cohort. # Patients will be monitored for Adverse Events which will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) 4.03. Treatment guidelines are given for any immune related or infusion related events. Adverse Event review will take place weekly during CRT and at every pembrolizumab visit as well as key time during follow up.
Patient reported outcomes will be assessed using the European Organisation for Research and Treatment of Cancer (EORTC) tool during CRT, pembrolizumab treatment and follow up. Patients will be followed up for 12 months.
266 studies on the registry are indexed under Anus Neoplasms; 71 are open to participants now.
This study's enrollment of 52 is below the median of 70 across 182 interventional studies indexed under Anus Neoplasms.
Browse Anus Neoplasms studies →Cardiff University is the lead sponsor of 43 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
In order to be eligible for participation in this trial, the subject must:
Demonstrate adequate organ function performed within 10 days of treatment initiation:
Exclusion Criteria:
The subject must be excluded from participating in the trial if the subject:
Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
Patients with locally advanced (stage IIIA/B, T3/T4, any N, M0) anal cancer will receive pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT.
Drug: Pembrolizumab
Pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T3/4 anal cancer.
Also known as: Radiotherapy, Chemotherapy (Mytomycin or Mitomycin and Capecitabine)
Safety and tolerability- 30 days post CRT
To assess safety of different schedules of exposure to pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T 3/4 anal cancer. Grade 3 to 5 treatment related adverse events (CTCAE - v.4.03) will be reported at 30 days post chemoradiotherapy.
Time frame: 30 days post chemoradiotherapy
Safety and tolerability- 6 weeks post CRT
To assess the safety of different schedules of exposure to pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T3/4 anal cancer. Grade 3 to 5 treatment related adverse events (CTCAE v.4.03) will be reported at 6 weeks post chemoradiotherapy.
Time frame: 6 weeks post chemoradiotherapy
Safety and tolerability - 12 weeks post CRT
To assess the safety of different schedules of exposure to pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T3/4 anal cancer. Grade 3 to 5 treatment related adverse events (CTCAE v.4.03) will be reported at 12 weeks post chemoradiotherapy.
Time frame: 12 weeks post chemoradiotherapy
Safety and tolerability - 6 months post CRT
To assess the safety of different schedules of exposure to pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T3/4 anal cancer. Grade 3 to 5 treatment related adverse events (CTCAE v.4.03) will be reported at 6 months post chemoradiotherapy.
Time frame: 6 months post chemoradiotherapy
Safety and tolerability- 9 months post CRT
To assess the safety and of different schedules of exposure to pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T3/4 anal cancer. Grade 3 to 5 treatment related adverse events (CTCAE Adverse Events v.4.03) will be reported at 9 months post chemo-radiotherapy.
Time frame: 9 months post chemoradiotherapy
Safety and tolerability- 12 months post CRT
To assess the safety of different schedules of exposure to pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T3/4 anal cancer. Grade 3 to 5 treatment related adverse events (CTCAE v.4.03) will be reported at 12 months post chemoradiotherapy.
Time frame: 12 months post chemoradiotherapy
Adherence to protocol treatment
Adherence to protocol treatment will be assessed by numbers of patients receiving per protocol treatment, dose delays, treatment reductions, treatment discontinuation and documenting the reasons for delays or discontinuation for each patient.
Time frame: Up to 6 months post chemoradiotherapy
Recruitment
Recruitment rate will be assessed by the number of days study is open for recruitment, the number of patients screened, the number of screened patients not recruited and why and the number (proportion) of patients recruited.
Time frame: 2 years
Retention
Retention will be assessed by the proportion of patients withdrawing from protocol treatment and number of patients lost to follow-up with documentation of reasons in each case.
Time frame: Up to 12 months post chemoradiotherapy
Study eligibility
Study eligibility will be assessed by the number of patients eligible and ineligible at screening and reasons for ineligibility.
Time frame: 2 years
Clinical response assessment - 3 months post CRT
Clinical response assessment will be measured by RECIST v 1.1 (MRI) for the overall response rate (ORR) at 3 months post chemoradiotherapy.
Time frame: 3 months post chemoradiotherapy
Clinical response assessment - 6 months post CRT
Clinical response assessment will be measured by RECIST v 1.1 (MRI) for the overall response rate (ORR) at 6 months post chemoradiotherapy.
Time frame: 6 months post chemoradiotherapy
Clinical response assessment - 12 months follow up
Clinical response assessment will be measured by RECIST v 1.1 (MRI) for the overall response rate (ORR) at 12 months follow up
Time frame: 12 months follow up
Imaging response - 3 months post CRT
Imaging response will be assessed by Tumor Regression Grade MRI by changes in Apparent Diffusion Coefficient (ADC) on DW sequences. Immune related modified RECIST assessments (MRI) at 3 months post chemoradiotherapy.
Time frame: 3 months post chemo-radiotherapy
Imaging response - 6 months post CRT
Imaging response will be assessed by Tumor Regression Grade MRI by changes in Apparent Diffusion Coefficient (ADC) on DW sequences. Immune related modified RECIST assessments (MRI) at 6 months post chemoradiotherapy.
Time frame: 6 months post chemoradiotherapy
Imaging response - 12 months follow up
Imaging response will be assessed by Tumor Regression Grade MRI by changes in Apparent Diffusion Coefficient (ADC) on DW sequences. Immune related modified RECIST assessments (MRI) at 12 months follow up.
Time frame: 12 months follow up
Patient reported outcome - up to 6 months post CRT
Patient-reported outcomes (PRO) will be measured by using the EORTC quality of life questionnaires during CRT and 6 months post-CRT.
Time frame: Up to 6 months post chemoradiotherapy
Patient reported outcome - 12 months follow up
Patient-reported outcomes (PRO) will be measured by using the EORTC quality of life questionnaires at 12 months follow up
Time frame: 12 months follow up
Plan to share: Undecided
No publications or documents are linked to this record.
This study is active, not recruiting, as verified in Jul 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Cardiff University