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

NCT04768504 | Terminated Phase 2

• 1 other identifier: CR2108KE
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Immune-Mediated Colitis

Keywords

Immune-related adverse events; Immune-related colitis

Outcome Measures

Primary Outcomes (1)

• Clinical Remission of Diarrhea

  Resolution of diarrhea to grade 1 or less per Common Terminology Criteria for Adverse Events

  8 weeks from first dose

Secondary Outcomes (4)

• Safety of tofacitinib

  from first dose to 30 days post last dose

• Endoscopic remission

  At 8 weeks

• Time to clinical remission

  from baseline to 8 weeks post first dose

• Tumor response status

  8 weeks from first dose

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Tofacitinib 10 mg PO BID for 30 days

Drug: Tofacitinib 10 mg

Interventions

Tofacitinib 10 mg DRUG

Tofacitinib 10 mg PO BID for 30 days

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older.
• Able to provide informed consent.
• Diagnosis of a solid tumor treated with an immune checkpoint inhibitor (ICI), with the exception of colorectal cancer.
• Exposure to an ICI (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.
• Current diagnosis of immune-related colitis characterized by grade ≥ 2 diarrhea as per CTCAE v5.0.
• 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.
• Adequate hematological function, defined by:
• hemoglobin ≥ 90 g/L
• absolute neutrophil count ≥ 1.0 x 109/L
• lymphocyte count ≥ 0.5 x 109/L
• platelets ≥ 75 x 109/L
• PT, PTT, INR ≤ 1.5 x upper limit of normal (ULN).
• 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.
• Adequate renal function as defined by an estimated clearance ≥ 40 mL/min, calculated per the Cockroft-Gault formula (appendix 2).
• Women of childbearing potential (WOCBP) are eligible if they agree to use adequate contraception while on study. If in line with the patient's preference and usual lifestyle, complete abstinence from heterosexual intercourse is acceptable. WOCBP must otherwise agree to correctly and consistently use at least one "highly effective" in addition to one "effective" contraceptive methods:

You may not qualify if:

• Diagnosis of a thromboembolic event (deep vein thrombosis, pulmonary embolism, embolic stroke, myocardial infarction, or peripheral arterial insufficiency) within 3 months of enrollment.
• 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.
• Any other grade ≥ 3 infection at the time of enrollment.
• Prior therapy with a JAK inhibitor within 3 months preceding enrollment.
• Use of strong inducers of CYP3A4 within 7 days of starting treatment with tofacitinib (see appendix 3).
• Known allergy or hypersensitivity to tofacitinib, its excipients or any of the drugs used in this study (valacyclovir, heparin, trimethoprim and sulfonamides).
• Active pregnancy or breastfeeding.
• Patients on intravenous biologic agents for other baseline autoimmune conditions.
• Patients having other concomitant uncontrolled irAEs at the time of enrollment which would require systemic corticosteroids or biologic immunomodulatory agents.

Sponsors & Collaborators

• Khashayar Esfahani: lead

Study Sites (1)

Sir Mortimer B Davis Jewish General Hospital - CIUSSS Centre-Ouest

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (1)

• Esfahani K, Hudson M, Batist G. Tofacitinib for Refractory Immune-Related Colitis from PD-1 Therapy. N Engl J Med. 2020 Jun 11;382(24):2374-2375. doi: 10.1056/NEJMc2002527. No abstract available.

  PMID: 32521140 BACKGROUND

MeSH Terms

Interventions

tofacitinib

Study Officials

• Khashayar Esfahani, MD

  Jewish General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: February 20, 2021
• First Posted: February 24, 2021
• Study Start: March 22, 2022
• Primary Completion: January 17, 2024
• Study Completion: January 17, 2024
• Last Updated: November 25, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)