Tofacitinib for the Treatment of Refractory Immune-related Colitis From Checkpoint Inhibitor Therapy- TRICK Study

Study Purpose

This is a single-arm pilot study evaluating the efficacy and safety of tofacitinib in cancer patients with immune-related colitis from immune checkpoint inhibitor (ICI) therapy.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria. 1. 18 years of age or older. 2. Able to provide informed consent. 3. Exposure to an immune checkpoint inhibitor (CTLA-4, PD-1, PDL-1) as part of a cancer treatment regimen within 6 months of the onset of colitis symptoms. The ICI may be used as a single agent, or in combination with other ICIs, or with chemotherapy. 4. Current diagnosis of immune-related colitis characterized by grade ≥ 2 diarrhea as per CTCAE v5.0. 5. Patients should have failed corticosteroids (at least 1mg/kg equivalent of prednisone for a minimum of 72 hours), and at least one dose of a biologic agent (i.e. either a TNFα inhibitor or an anti-integrin). Failure is defined as having ongoing grade ≥ 2 diarrhea per CTCAE v5.0. 6. Adequate hematological function, defined by: 1. hemoglobin ≥ 90 g/L. 2. absolute neutrophil count ≥ 1.0 x 109/L. 3. lymphocyte count ≥ 0.5 x 109/L. 4. platelets ≥ 75 x 109/L. 5. PT, PTT, INR ≤ 1.5 x upper limit of normal (ULN). 7. Adequate liver function, as assessed by the Child Pugh classification score (appendix 1). Patients with scores A and B are eligible for enrollment. Patients with severe hepatic impairment (Child Pugh C) are excluded from the study. 8. Adequate renal function as defined by an estimated clearance ≥ 40 mL/min, calculated per the Cockroft-Gault formula (appendix 2). 9. Women of childbearing potential (WOCBP) are eligible if they agree to use adequate contraception while on study. Exclusion criteria. Patients should meet none of the following exclusion criteria to be eligible for this study: 1. Diagnosis of a thromboembolic event (deep vein thrombosis, pulmonary embolism, embolic stroke, myocardial infarction, or peripheral arterial insufficiency) within 3 months of enrollment. 2. Diagnosis of concomitant infectious colitis (e.g. C. Difficile or other bacterial source), unless the patient has finished an appropriate length of treatment with antibiotics as indicated for each diagnosis at the time of enrollment. 3. Any other grade ≥ 3 infection at the time of enrollment. 4. Prior therapy with a JAK inhibitor within 3 months preceding enrollment. 5. Active pregnancy or breastfeeding. 6. Patients on intravenous biologic agents for other baseline autoimmune conditions. 7. Patients having other concomitant uncontrolled irAEs at the time of enrollment which would require systemic corticosteroids or biologic immunomodulatory agents.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04768504
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Khashayar Esfahani
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Khashayar Esfahani, MD
Principal Investigator Affiliation Jewish General Hospital
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Not yet recruiting
Countries
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Immune-Mediated Colitis
Additional Details

Primary objective and endpoint. • Efficacy of tofacitinib in inducing clinical remission of immune related colitis, as measured by the proportion of patients who experience diarrhea resolution to grade ≤1 as per Common Terminology Criteria for Adverse Events [CTCAE] v5.0) without the requirement for additional immunosuppression (e.g., corticosteroids, biologics, or other immunosuppressors targeted for colitis) 8 weeks post-first dose of tofacitinib. Secondary objectives and endpoints:

  • - Safety of tofacitinib in cancer patients with immune-related colitis, as defined by the occurrence of adverse events grade ≥3.
  • - Efficacy of tofacitinib in cancer patients with immune colitis as defined by endoscopic remission of colitis (a total Mayo score of ≤2) at 8 weeks.
  • - Efficacy of tofacitinib to induce a clinical remission of immune-related colitis as measured by the time, in days, necessary to achieve a diarrhea of grade ≤ 1 (as per CTCAE v 5.0).
  • - Number of patients with tumor progression at 8 weeks per iRECIST and RECIST 1.1 criteria compared to baseline scans.
Exploratory objective. • The study will collect blood samples from participants seeking to characterize the inflammatory landscape of ICI-mediated colitis and biomarkers predictive of response to tofacitinib.

Arms & Interventions

Arms

Experimental: Treatment Arm

Tofacitinib 10 mg PO BID for 30 days

Interventions

Drug: - Tofacitinib 10 mg

Tofacitinib 10 mg PO BID for 30 days

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

Faheem Khiyani

faheem.khiyani.ccomtl@ssss.gouv.qc.ca

514-340-8222

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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