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

• Status: Recruiting
• Trial end date: 2023-09-30
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Khashayar Esfahani
• Treatments: Tofacitinib

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.