The purpose of this study is to assess the prevention of immune checkpoint inhibitors (ICI) related diarrhea/colitis using vedolizumab in participants with unresectable stage III or metastatic stage IV cancer, starting standard of care (SOC) immunotherapy
VERIFY is a multicenter, prospective, randomized, double-blinded, placebo-controlled, parallel group superiority trial, evaluating the efficacy and safety of vedolizumab, a monoclonal antibody targeting the α4β7 integrin receptor specific to gut-targeted T-lymphocytes, for the prevention of ICI-related diarrhea and colitis in participants with unresectable melanoma, lung, or renal cancer starting immunotherapy who are at high risk, defined by the development of an elevated fecal calprotectin \>100 μg/g within 4 weeks of the first ICI dose. Eligible participants will be randomized 1:1 to receive 6 months of vedolizumab or placebo, administered as prophylaxis therapy in addition to continuing ICI treatment (administered at weeks 0, 2, 6, 14, and 22). Participants will then be followed for 1 year.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
36
300 mg IV at weeks Baseline (Week 0) Weeks 2, 6, 14, and 22.
300 mg IV at Baseline (Week 0) Weeks 2, 6, 14, and 22.
Arthur J.E. Child Comprehensive Cancer Centre
Calgary, Alberta, Canada
RECRUITINGCross Cancer Institute
Edmonton, Alberta, Canada
NOT_YET_RECRUITINGTo establish the feasibility of the VERIFY protocol and determine progression to the full trial
Feasibility defined by achievement of all pre-specified progression criteria: * Recruitment \>75% target (\>0.53 participants per site per month achieving randomization) * Recruitment: fecal calprotectin after first dose of ICI therapy \>100 μg/g in at least 15% of screened participants * Protocol adherence: \>95% of randomized participants receiving allocated treatment, protocol adherence in \>90% * Outcome data quality: endoscopy and biopsies taken in \>90% of eligible participants, \<10% loss to follow-up * Feedback: no major concerns identified by patients or providers on acceptability survey * \>15% of placebo-treated participants developing the primary outcome (sufficient event rate for feasible prevention) * Rate of PFS and OS is not lower than historical estimates from a similar population
Time frame: Up to 5 years
To evaluate feasibility of recruitment
• Mean time to site initiation
Time frame: Up to 5 years
To evaluate feasibility of recruitment
• Number of screened participants
Time frame: Up to 5 years
To evaluate feasibility of recruitment
• Screen failure rate and qualitative assessment of reasons for screen failure
Time frame: Up to 5 years
To evaluate feasibility of recruitment
• Qualitative assessment of reasons for screen failure
Time frame: Up to 5 years
To evaluate feasibility of adhering to the protocol
Adherence feasibility metrics will include: * Proportion of participants receiving the allocated treatment within 2 weeks of randomization * Proportion of participants adhering to the follow-up schedule
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Time frame: Up to 5 years
To evaluate feasibility of adhering to the protocol
Adherence feasibility metrics will include: • Number and qualitative description of minor and major protocol deviations
Time frame: Up to 5 years
To evaluate feasibility of obtaining high quality outcome data
Outcome measure feasibility metrics will include: * Proportion of eligible participants undergoing lower endoscopy and biopsies to confirm histologic ICI-related colitis * Proportion of participants lost to follow-up and qualitative assessment of reasons for loss to follow-up
Time frame: Up to 5 years
To evaluate the incidence of diarrhea and colitis in the placebo group
Feasibility of prevention metrics will include: * Proportion of participants receiving placebo who develop CTCAE grade ≥2 diarrhea/colitis * Proportion of participants receiving placebo who develop CTCAE grade ≥3 diarrhea/colitis * Proportion of participants receiving placebo who develop CTCAE any grade diarrhea/colitis
Time frame: Up to 1 year
To evaluate the efficacy of concomitant vedolizumab and ICI therapy
To ensure that there is no interaction between vedolizumab and efficacy of ICI therapy, evaluation will include: • Progression free survival and overall survival in the vedolizumab group (compared to a historical control population)
Time frame: Up to 1 year