Role of Gut Microbiome and Fecal Transplant on Medication-Induced GI Complications in Patients With Melanoma or Genitourinary Cancer
Keywords
Abstract
Description
PRIMARY OBJECTIVES:
I. To compare the difference in stool microbiome pattern between patients who develop immune-checkpoint inhibitor (ICPI)-related colitis and patients who don't develop ICPI-related colitis.
II. To compare the difference in stool microbiome pattern in patients who developed ICPI-related colitis before and after colitis medical treatment.
SECONDARY OBJECTIVES:
I. To identify and characterize immune profile and genetic factors associated with onset of ICPI-related colitis in blood and colon tissue.
II. To identify and characterize immune profile and genetic factors in blood and colon tissue that are associated with quick response of ICPI-related colitis to medical treatment.
III. To characterize the endoscopic and histologic features of ICPI-related colitis before and after medical treatment.
IV. To assess stool microbiome features that are associated with good response to fecal microbiota transplantation.
V. To assess the factors in genetic/immune profile obtained from blood and colon tissue that are associated with good response to fecal microbiota transplantation.
VI. To characterize the endoscopic and histologic features of ICPI-related colitis before and after fecal microbiota transplantation.
VII. To assess the adverse events related to fecal microbiota transplantation.
EXPLORATORY OBJECTIVES:
I. To identify and characterize immune profile and genetic factors associated with onset of ICPI-related colitis in inflamed colonic mucosa and its matched normal mucosa.
II. To characterize the immune profile and genetic factors from the colon tissue in these colitis patients among different histological subtypes.
III. To assess the pattern of stool microbiome that is associated with good tumor response to ICPI treatment.
IV. To assess the association between stool inflammatory markers (i.e. lactoferrin and calprotectin) and the severity of endoscopic/histologic inflammation.
V. To assess the sensitivity and specificity of stool inflammatory markers (i.e. lactoferrin and calprotectin) as an indicators of ICPI-relate colitis response to treatment.
VI. To assess the microbiome pattern that triggers the infections on immunosuppressant treatment for ICPI colitis.
OUTLINE:
PROJECT 1: Patients receive standard of care and undergo collection of stool and blood samples.
PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection of stool, blood, and tissue samples.
PROJECT 3: Patients undergo fecal microbiota transplant (FMT).
After completion of study, patients are followed up periodically.
Dates
| Last Verified: | 01/31/2020 |
| First Submitted: | 01/24/2019 |
| Estimated Enrollment Submitted: | 01/24/2019 |
| First Posted: | 01/27/2019 |
| Last Update Submitted: | 02/03/2020 |
| Last Update Posted: | 02/05/2020 |
| Actual Study Start Date: | 02/14/2020 |
| Estimated Primary Completion Date: | 06/30/2022 |
| Estimated Study Completion Date: | 06/30/2022 |
Condition or disease
Intervention/treatment
Other: Supportive Care (standard of care, sample collection, FMT)
Other: Supportive Care (standard of care, sample collection, FMT)
Procedure: Supportive Care (standard of care, sample collection, FMT)
Procedure: Supportive Care (standard of care, sample collection, FMT)
Biological: Supportive Care (standard of care, sample collection, FMT)
Other: Supportive Care (standard of care, sample collection, FMT)
Drug: Supportive Care (standard of care, sample collection, FMT)
Biological: Supportive Care (standard of care, sample collection, FMT)
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Supportive Care (standard of care, sample collection, FMT) PROJECT 1: Patients receive standard of care and undergo collection of stool and blood samples.
PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection of stool, blood, and tissue samples.
PROJECT 3: Patients undergo FMT. | Other: Supportive Care (standard of care, sample collection, FMT) Receive standard of care |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - Diagnosis of any stage melanoma or genitourinary (GU) malignancies. - Treatment with any ICPI agent. - Ability to understand and willingness to sign an informed consent form. - Life expectancy > 4 months. - PROJECT 1: ICPI-related diarrhea/colitis of any grade with or without concurrent non GI toxicity as the toxicity group. - PROJECT 1: Patients with no organ toxicity as the control group. - PROJECTS 2 AND 3: ICPI-related colitis of grade 2 or above as GI toxicity without involvement of non GI toxicity. - PROJECT 3: ICPI-related colitis with ANY of the following characteristics: (1) refractory to treatment of steroid and two doses of non-steroidal immunosuppressants e.g. infliximab and/or vedolizumab; (2) contraindication for immunosuppressive treatment; or (3) recurrence after successful initial treatment. Exclusion Criteria: - Age younger than 18 years - Positive GI infection at the onset of ICPI-related GI toxicity. - History of inflammatory bowel disease, and/or radiation enteritis or colitis. - Pregnant and breastfeeding women. - Women of child-bearing potential who have positive urine or serum pregnancy test or refuse to do pregnancy test. - PROJECT 2: Patients who have a contraindication for immunosuppressive treatment. - PROJECT 2: Patients who develop concurrent or only non GI toxicity. - PROJECT 3: Patients with active bacterial or fungal infection. |
Outcome
Primary Outcome Measures
1. Incidence of adverse events (AEs) [Up to 4 months]
2. Incidence of toxicities (Project 3) [Up to 1 year]
