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

Официальное название

VERIFY: Vedolizumab for the Prevention of Immune Checkpoint Inhibitor Related Diarrhea or Colitis in Patients With Cancer: A Randomized, Double-Blinded, Placebo Controlled Trial

Обзор

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

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Hazard Ratio of Patients achieving ICI-related diarrhea and colitis-free survival a 6-months [Срок оценки: Start of immunotherapy therapy and for 6 months]

Вторичные конечные точки (12)

• Proportion of patients with histologically confirmed colitis-free survival at 6 months [Срок оценки: 6 months]
• Proportion of patients with severe diarrhea or colitis at 6 months [Срок оценки: 6 months]
• Hazard Ratio of patients with diarrhea or colitis after 6 months [Срок оценки: 6-12 months]
• Total average dose of checkpoint inhibitor therapy received within 6 and 12 months [Срок оценки: 0 to 6 months; and 0 to 12 months]
• Proportion of participants who require temporary ICI discontinuation due to immune-related adverse events (irAEs) [Срок оценки: 0 to 12 months]
• Proportion of participants who require permanent ICI discontinuation due to irAEs [Срок оценки: 0 to 12 months]
• Proportion of patients requiring rescue corticosteroids for ICI related diarrhea/colitis [Срок оценки: at 6-months and 12-months]
• Total average prednisone equivalent dose of rescue corticosteroids required [Срок оценки: at 6-months and 12-months]
• Proportion of participants requiring all-cause hospitalization by Day +180 and Day +365 [Срок оценки: at day 180 and 365]
• Proportion of participants requiring ICI-related diarrhea/colitis-specific hospitalization by Day +180 and Day +365 [Срок оценки: at day 180; at day 365]
• Mean change in the EuroQol EQ-5D instrument at Day +180 and Day +365 compared to baseline [Срок оценки: baseline to day 180; baseline to day 365]
• Overall survival (measured as death) at +180 and Day +365 compared to baseline [Срок оценки: Day +180 and Day +365]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06337695 · HREBA.CC-23-0271

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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