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

Cancer Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06337695
• Other study ID #: HREBA.CC-23-0271
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: July 1, 2024
• Est. completion date: December 1, 2026

Study information

• Verified date: October 2023
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 298
• Est. completion date: December 1, 2026
• Est. primary completion date: November 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer
• Cancer Metastatic
• Colitis
• Diarrhea

Intervention

Biological:
• Vedolizumab
300 mg IV at weeks 0, 3, 6, 14, and 22
• Placebo
300 mg IV at weeks 0, 3, 6, 14, and 22

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Calgary

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Start of immunotherapy therapy and for 6 months
Secondary	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.	6 months
Secondary	Proportion of patients with severe diarrhea or colitis at 6 months	Severe diarrhea or colitis will be defined as CTCAE grade =3	6 months
Secondary	Hazard Ratio of patients with diarrhea or colitis after 6 months	Diarrhea or colitis will be defined as CTCAE grade =2	6-12 months
Secondary	Total average dose of checkpoint inhibitor therapy received within 6 and 12 months	The total average dose of ICI therapy will be used	0 to 6 months; and 0 to 12 months
Secondary	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).	0 to 12 months
Secondary	Proportion of participants who require permanent ICI discontinuation due to irAEs	Permanent discontinuation of ICI therapy will be defined as stopping ICI therapy, and not restarting within the 1-year time window of the trial resulting from an immune-related adverse event (irAE), as identified and graded using the Common Terminology Criteria for Adverse Events (CTCAE v5.0).	0 to 12 months
Secondary	Proportion of patients requiring rescue corticosteroids for ICI related diarrhea/colitis	Any patient who receives rescue corticosteroids within the first 6 months or within the first 12 months will be considered an event.	at 6-months and 12-months
Secondary	Total average prednisone equivalent dose of rescue corticosteroids required	The prednisone equivalent dose will be calculated using the following conversions: Cortisone 5mg = Prednisone 1mg Hydrocortisone 4mg = Prednisone 1mg Prednisolone 1mg = Prednisone 1mg Methylprednisolone 0.8mg = Prednisone 1mg Dexamethasone 0.15mg = Prednisone 1mg	at 6-months and 12-months
Secondary	Proportion of participants requiring all-cause hospitalization by Day +180 and Day +365	Chart review will be used to identify hospitalizations.	at day 180 and 365
Secondary	Proportion of participants requiring ICI-related diarrhea/colitis-specific hospitalization by Day +180 and Day +365	Chart review will be used to identify hospitalization and determine the cause of hospitalization.	at day 180; at day 365
Secondary	Mean change in the EuroQol EQ-5D instrument at Day +180 and Day +365 compared to baseline	The EuroQol EQ-5D is a validated questionnaire for patients with inflammatory bowel disease.	baseline to day 180; baseline to day 365
Secondary	Overall survival (measured as death) at +180 and Day +365 compared to baseline	All-cause mortality will be used to compare the survival rate of the therapy and placebo arms. The rates will be calculated for 6 months (defined at day 180) and 1-year (day 365).	Day +180 and Day +365
Secondary	Progression-free survival at 6- and 12-months, defined using the Response Evaluation Criteria in Solid Tumors (RECIST), v1.176	Progression-free survival will be defined using the Response Evaluation Criteria in Solid Tumors (RECIST), v1.176	At Day +180 and Day +365
Secondary	Proportion of participants experiencing any adverse events (AEs)	Adverse events will be defined as described in good clinical practice.	At Day +180 and Day +365
Secondary	Proportion of participants experiencing serious AEs	Serious adverse events will be defined as described in good clinical practice.	At Day +180 and Day +365
Secondary	Proportion of participants experiencing other irAEs	Adverse events will be defined as described in good clinical practice. Those that are immune related will be used for this outcome.	At Day +180 and Day +365