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Immune-Mediated ColitisPhase 2NCT04768504

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

A Phase 2 study testing Tofacitinib 10 mg in people with Immune-Mediated Colitis, run by Khashayar Esfahani at 1 site in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Immune-Mediated Colitis
What is being tested?
Tofacitinib 10 mg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteCanada
Study dates
22 Mar 2022to 17 Jan 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 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.
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  • 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:
  • Highly effective means of contraception include the following:
  • Hormonal methods of contraception including combined oral contraceptives, vaginal ring, injectables, patch, implants, and intrauterine systems (IUSs).
  • Nonhormonal intrauterine devices (IUDs).
  • Tubal ligation
  • Vasectomy of the sole partner of a female subject
  • Male condoms with spermicide
  • Effective means of contraception include the following:
  • Diaphragm with spermicide
  • Cervical cap with spermicide
  • Vaginal contraceptive sponge
  • Male condom without spermicide
  • Female condom (a male and female condom must not be used together)

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

1 site in 1 country.

Canada1 site

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

    Montreal, Quebec, H3T 1E2

Other trials in Canada

About this study

Official title: An Open-label Study of Tofacitinib for the Treatment of Refractory Immune-related Colitis from ChecKpoint Inhibitor Therapy (TRICK)

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.

Read the detailed description

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.
Being tested
Tofacitinib 10 mg
Keywords
Immune-related adverse events, Immune-related colitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tofacitinib 10 mgDrug

    Tofacitinib 10 mg PO BID for 30 days

Study groups in NCT04768504
Study groupRoleWhat they receive
Treatment ArmExperimentalTofacitinib 10 mg PO BID for 30 days
Receives: Drug: Tofacitinib 10 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical Remission of Diarrhea

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

    Measured: 8 weeks from first dose

Secondary outcomes (4)

  1. Safety of tofacitinib

    Defined as the occurrence of Grade 3 or higher adverse events

    Measured: from first dose to 30 days post last dose

  2. Endoscopic remission

    per Mayo score of less or equal than 2

    Measured: At 8 weeks

  3. Time to clinical remission

    time in days to resolution of diarrhea to grade 1 or less

    Measured: from baseline to 8 weeks post first dose

  4. Tumor response status

    number of patient with PD by RECIST/iRECIST criteria

    Measured: 8 weeks from first dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Feb 2021
  2. Study start22 Mar 2022
  3. Primary completion17 Jan 2024
  4. Study completion17 Jan 2024

Why it stopped: sponsor decision, due to low recruitment rate

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04768504
Sponsor's protocol ID
CR2108KE
Status last verified
Nov 2024
First submitted
20 Feb 2021
Last updated
25 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32521140

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tofacitinib 10 mg in people with Immune-Mediated Colitis, run by Khashayar Esfahani at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: sponsor decision, due to low recruitment rate). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Remission of Diarrhea (time frame: 8 weeks from first dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04768504, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2024.

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