Role of Gut Microbiome and Fecal Transplant on Medication-Induced GI Complications in Patients With Cancer

Launched by M.D. ANDERSON CANCER CENTER · Jan 25, 2019

Keywords

ClinConnect Summary

This clinical trial is examining how the gut microbiome, which is the collection of bacteria and other microorganisms in our digestive system, affects gastrointestinal (GI) problems caused by certain cancer medications. Specifically, it looks at whether fecal transplants can help improve issues like diarrhea and colitis (inflammation of the intestines) that some patients experience while undergoing treatment for melanoma or genitourinary cancers. By analyzing samples of stool, blood, and tissue from patients, researchers hope to better understand how these treatments work and how they affect the body.

To participate in this trial, patients need to be diagnosed with any stage of melanoma, non-small cell lung cancer, or other genitourinary cancers, and must have experienced GI complications from treatment with immune-checkpoint inhibitors (a type of cancer medication). Eligible participants must also be willing to provide informed consent and may be receiving standard treatments for their symptoms. Throughout the study, participants will be monitored closely and can withdraw at any time if they choose. This research aims to find new ways to help manage the side effects of cancer treatments and improve patients' overall comfort during their care.

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Eligibility criteria

• Inclusion Criteria:
• • 1. Diagnosis of any stage melanoma, Non-Small Cell Lung Cancer or genitourinary (GU) malignancies (Project 1).
• • 2. Diagnosis of any cancer type (Projects 2 and 3)
• • 3. Treatment with any ICPI agent
• • 4. Ability to understand and willingness to sign an informed consent form and rate surveys
• • 5. Life expectancy \> 4 months (Project 3)
• • 6. ICPI-related diarrhea and/or colitis of any grade with or without concurrent non- GI toxicity as the toxicity group (project 1)
• • 7. Patients with no organ toxicity as the control group (project 1)
• • 8. ICPI-related colitis and/or diarrhea of grade ≥ 2 as GI toxicity (initial episode or recurrence) receiving standard treatment of immunosuppressive agents (steroid, infliximab, vedolizumab, or ustekinumab) any time during the colitis disease course until sustained resolution of GI toxicity, or one- year time point after enrollment (Project 2)
• • 9. ICPI-related colitis and/or diarrhea of grade ≥ 2 as GI toxicity without involvement of non- GI toxicity within 45 days prior to FMT (Project 3)
• 10. ICPI-related colitis and/or diarrhea of grade ≥ 2 within 45 days prior to FMT with ANY of the following characteristics (project 3):
• • (i) refractory to treatment of steroid and two doses of non-steroidal immunosuppressants e.g. infliximab, vedolizumab or ustekinumab,
• • (ii) contraindication for immunosuppressive treatment,
• • (iii) recurrence after successful initial treatment,
• • (iv) recurrent symptoms once steroid is tapered down/off or diarrhea/colitis symptoms are steroid dependent, or
• • (v) patients with a history of refractory ICPI-related colitis and/or diarrhea to medical treatment, even if they have improved symptoms from supportive care within 45 days prior to FMT
• • 11. No concern for active concomitant GI infection for the ICPI diarrhea/colitis work up at the time of protocol therapy initiation as confirmed by stool tests or as per the treating physician based on clinical presentation (project 3)
• • 12. Patient who has been cleared for enrollment by Infectious Diseases consultant or treating physician if positive infection workup or screening tests (e.g. lifelong positive T-spot due to BCG inoculation, chronic colonization) prior to initiation of diarrhea/colitis treatment (project 3)
• Exclusion Criteria:
• • 1. Age younger than 18 years
• • 2. History of inflammatory bowel disease, and/or radiation enteritis or colitis with active disease status at the time of study treatment initiation
• • 3. Pregnant and breastfeeding women
• • 4. Women of child-bearing potential who have positive urine or serum pregnancy test or refuse to do pregnancy test unless last menstrual cycle was \> 1 year prior to consent and/ or clear documentation states that patient is peri- or post-menopausal or there was recent supporting objective evidence of 'no pregnancy' status (e.g. blood or imaging) within 30 days prior to date of study treatment
• • 5. Patients who develop concurrent non- GI toxicity at the time of FMT treatment (project 3)
• • 6. Patients with active bacterial or fungal infection (Project 3)
• • 7. Donors at risk for monkeypox infection and/ or exposure as determined by a questionnaire (Project 3)
• • Withdrawal Criteria
• • 1. Patients may withdraw from the trial at any time
• • 2. Patients who develop GI perforation or toxic colitis that require surgery from ICPI colitis
• • 3. In project 3, if the first 30% of cases fail the fecal transplant treatment, then project 3 will be terminated