Clinical trial NCT06337695: VERIFY: Vedolizumab for the Prevention of Immune Checkpoint Inhibitor Related Diarrhea or Colitis in Patients With Cancer
Official title: VERIFY: Vedolizumab for the Prevention of Immune Checkpoint Inhibitor Related Diarrhea or Colitis in Patients With Cancer: A Randomized, Double-Blinded, Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Cancer
Cancer Metastatic
Keywords: Immune Checkpoint Inhibitors
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2024-03-29
Enrollment: 298
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A Randomized, Double-Blinded, Placebo Controlled Trial
Primary purpose: PREVENTION

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Hazard Ratio of Patients achieving ICI-related diarrhea and colitis-free survival a 6-months
timeFrame: Start of immunotherapy therapy and for 6 months
Secondary outcomes:
measure: Proportion of patients with histologically confirmed colitis-free survival at 6 months
timeFrame: 6 months
measure: Proportion of patients with severe diarrhea or colitis at 6 months
timeFrame: 6 months
measure: Hazard Ratio of patients with diarrhea or colitis after 6 months
timeFrame: 6-12 months
measure: Total average dose of checkpoint inhibitor therapy received within 6 and 12 months
timeFrame: 0 to 6 months; and 0 to 12 months
measure: Proportion of participants who require temporary ICI discontinuation due to immune-related adverse events (irAEs)
timeFrame: 0 to 12 months
measure: Proportion of participants who require permanent ICI discontinuation due to irAEs
timeFrame: 0 to 12 months
measure: Proportion of patients requiring rescue corticosteroids for ICI related diarrhea/colitis
timeFrame: at 6-months and 12-months
measure: Total average prednisone equivalent dose of rescue corticosteroids required
timeFrame: at 6-months and 12-months
measure: Proportion of participants requiring all-cause hospitalization by Day +180 and Day +365
timeFrame: at day 180 and 365
measure: Proportion of participants requiring ICI-related diarrhea/colitis-specific hospitalization by Day +180 and Day +365
timeFrame: at day 180; at day 365
measure: Mean change in the EuroQol EQ-5D instrument at Day +180 and Day +365 compared to baseline
timeFrame: baseline to day 180; baseline to day 365
measure: Overall survival (measured as death) at +180 and Day +365 compared to baseline
timeFrame: Day +180 and Day +365
measure: Progression-free survival at 6- and 12-months, defined using the Response Evaluation Criteria in Solid Tumors (RECIST), v1.176
timeFrame: At Day +180 and Day +365
measure: Proportion of participants experiencing any adverse events (AEs)
timeFrame: At Day +180 and Day +365
measure: Proportion of participants experiencing serious AEs
timeFrame: At Day +180 and Day +365
measure: Proportion of participants experiencing other irAEs
timeFrame: At Day +180 and Day +365
Other outcomes:
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