VERIFY: Vedolizumab for the Prevention of Immune Checkpoint Inhibitor Related Diarrhea or Colitis in Patients With Cancer

Phase 3Not Yet RecruitingNCT06337695

University of Calgary298 enrolled

Overview

The purpose of this study is to assess the prevention of immune checkpoint inhibitors (ICIs) related diarrhea/colitis using vedolizumab in participants with unresectable stage III or metastatic stage IV cancer, starting standard of care (SOC) immunotherapy

After being informed about the study and potential risks, all patients giving written informed consent will undergo up to a 2-week screening period to confirm their eligibility. Eligible patients will be randomized in a double-blind manner (participant and investigator) in a 1:1 ratio to Vedolizumab or placebo and given their first dose within 2 weeks of starting their SOC immunotherapy. Vedolizumab or placebo will be administered at Weeks 0, 2, 6, 14, and 22.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

298

Conditions

Cancer Cancer Metastatic

Interventions

VedolizumabBIOLOGICAL

300 mg IV at weeks 0, 3, 6, 14, and 22

PlaceboBIOLOGICAL

300 mg IV at weeks 0, 3, 6, 14, and 22

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Signed informed consent prior to initiation of any study specific activities or procedures * Diagnosed with unresectable advanced stage III or metastatic stage IV malignancy * Planned for initiation of SOC immunotherapy and development of prognostic biomarker evidence that predisposes to ICI diarrhea/colitis risk * Ability to and willingness to adhere to the randomized treatment interventions (vedolizumab or placebo), administered intravenously Exclusion Criteria: * Condition(s) for which vedolizumab is contraindicated (e.g., hypersensitivity reaction, known allergic reaction to vedolizumab or its components) * Current or prior use of vedolizumab or prior immunotherapy exposure for cancer * Presence of inflammatory bowel disease (Crohn's disease, ulcerative colitis), indeterminate colitis, or microscopic colitis * Presence of ileostomy, colostomy, or short bowel syndrome * Presence of known luminal gastrointestinal metastases at baseline * Presence of significant pre-existing autoimmune disease (at investigator's discretion) * Presence of severe infection(s) or opportunistic infection(s) * Active enteric infection with viral, bacterial, or parasitic pathogens * Presence of untreated latent or active tuberculosis, or untreated chronic hepatitis B virus * Baseline ECOG status grade ≥3 * Pregnancy or lactation * Treatment with another investigational product within 8 weeks of randomization * Requirement for baseline anti-diarrheal treatment(s) (including but not limited to loperamide, diphenoxylate-atropine, octreotide, tincture of opium), anticholinergic drug(s), or opioid-based analgesic(s) used specifically for diarrhea control within 14 days of randomization * Any condition or diagnosis, that could in the opinion of the Qualified Investigator or delegate interfere with the participant's ability to comply with study instructions, might confound the interpretation of the study results, or put the participant at risk

Outcomes

Primary Outcomes

Hazard Ratio of Patients achieving ICI-related diarrhea and colitis-free survival a 6-months

ICI-related diarrhea and colitis will be assessed using Common Terminology Criteria for Adverse Events (CTCAE), and a grade ≥2 will be considered an event.

Time frame: Start of immunotherapy therapy and for 6 months

Secondary Outcomes

Proportion of patients with histologically confirmed colitis-free survival at 6 months

Colitis-free survival will be defined as CTCAE grade ≥2 based on a biopsy taken at time of patient meeting the primary endpoint or at 6 months.

Time frame: 6 months

Proportion of patients with severe diarrhea or colitis at 6 months

Severe diarrhea or colitis will be defined as CTCAE grade ≥3

Time frame: 6 months

Hazard Ratio of patients with diarrhea or colitis after 6 months

Diarrhea or colitis will be defined as CTCAE grade ≥2

Time frame: 6-12 months

Total average dose of checkpoint inhibitor therapy received within 6 and 12 months

The total average dose of ICI therapy will be used

Time frame: 0 to 6 months; and 0 to 12 months

Proportion of participants who require temporary ICI discontinuation due to immune-related adverse events (irAEs)

Temporary discontinuation of ICI therapy will be defined as any delay of 1-week or more resulting from an immune-related adverse event (irAE), as identified and graded using the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

Time frame: 0 to 12 months

Data from ClinicalTrials.gov

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