VERIFY: Vedolizumab for the Prevention of Immune Checkpoint Inhibitor Related Diarrhea or Colitis in Patients With Cancer: A Randomized, Double-Blinded, Placebo Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Hazard Ratio of Patients achieving ICI-related diarrhea and colitis-free survival a 6-months
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
All participants and site personnel will be blinded to treatment assignment. Randomization procedures intended at preserving blinding include concealed random allocation sequence generation and blocked randomization.
The site research pharmacist will be unblinded to treatment assignment, in order to prepare the vedolizumab or placebo infusion. Masking of the infusion will be conducted by the site pharmacist, so that the patient and other site personnel remain blinded.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent prior to initiation of any study specific activities or procedures
- •Adult patient ≥18 years old
- •Diagnosed with unresectable advanced stage III or metastatic stage IV malignant melanoma, lung, or renal cancer
- •Planned for initiation of SOC treatment with any immunotherapy and develop an elevated fecal calprotectin > 100 μg/g within 4 weeks of first ICI dose
- •Ability to and willingness to adhere to the randomized treatment interventions (vedolizumab or placebo), administered intravenously
- •Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test at the time of screening. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes.
- •As per the Health Canada product monograph, WOCBP are strongly recommended to use adequate contraception to prevent pregnancy and to continue its use for at least 6 months after the last study visit.
- •Note: abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard.
排除标准
- •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
- •Presence of inflammatory bowel disease (Crohn's disease, ulcerative colitis), indeterminate colitis, segmental colitis associated with diverticulosis 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. If there is a clinical suspicion of either, it is at the discretion of the Investigator to order the appropriate work-up.
- •Baseline ECOG status grade ≥3
- •Pregnancy or lactation (no exclusion for pregnant partner)
- •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
结局指标
主要结局
Hazard Ratio of Patients achieving ICI-related diarrhea and colitis-free survival a 6-months
时间窗: Start of immunotherapy therapy and for 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.
To establish the feasibility of the VERIFY protocol and determine progression to the full trial
时间窗: Up to 5 years
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
次要结局
- Proportion of participants who require temporary ICI discontinuation due to immune-related adverse events (irAEs)(0 to 12 months)
- Proportion of participants requiring ICI-related diarrhea/colitis-specific hospitalization by Day +180 and Day +365(at day 180; at day 365)
- Proportion of participants experiencing any adverse events (AEs)(At Day +180 and Day +365)
- Proportion of patients with severe diarrhea or colitis at 6 months(6 months)
- Hazard Ratio of patients with diarrhea or colitis after 6 months(6-12 months)
- Proportion of participants experiencing serious AEs(At Day +180 and Day +365)
- Proportion of participants experiencing other irAEs(At Day +180 and Day +365)
- Mean change in the EuroQol EQ-5D instrument at Day +180 and Day +365 compared to baseline(baseline to day 180; baseline to day 365)
- Proportion of patients with histologically confirmed colitis-free survival at 6 months(6 months)
- Proportion of patients requiring rescue corticosteroids for ICI related diarrhea/colitis(at 6-months and 12-months)
- Total average prednisone equivalent dose of rescue corticosteroids required(at 6-months and 12-months)
- Progression-free survival at 6- and 12-months, defined using the Response Evaluation Criteria in Solid Tumors (RECIST), v1.176(At Day +180 and Day +365)
- Total average dose of checkpoint inhibitor therapy received within 6 and 12 months(0 to 6 months; and 0 to 12 months)
- Proportion of participants who require permanent ICI discontinuation due to irAEs(0 to 12 months)
- Proportion of participants requiring all-cause hospitalization by Day +180 and Day +365(at day 180 and 365)
- Overall survival (measured as death) at +180 and Day +365 compared to baseline(Day +180 and Day +365)
- To evaluate feasibility of recruitment(Up to 5 years)
- To evaluate feasibility of adhering to the protocol(Up to 5 years)
- To evaluate feasibility of obtaining high quality outcome data(Up to 5 years)
- To evaluate the incidence of diarrhea and colitis in the placebo group(Up to 1 year)
- To evaluate the efficacy of concomitant vedolizumab and ICI therapy(Up to 1 year)