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

NCT03819296 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2018-0383NCI-2018-03437
• Study Type: interventional
• Target: 800
• Locations: 1 country
• Sites: 1

Brief Summary

This trial studies the role of the gut microbiome and effectiveness of a fecal transplant on medication-induced gastrointestinal (GI) complications in patients with melanoma or genitourinary cancer. The gut microbiome (the bacteria and microorganisms that live in the digestive system) may affect whether or not someone develops colitis (inflammation of the intestines) during cancer treatment with immune-checkpoint inhibitor drugs. Studying samples of stool, blood, and tissue from patients with melanoma or genitourinary cancer may help doctors learn more about the effects of treatment on cells, and help doctors understand how well patients respond to treatment. Treatment with fecal transplantation may help to improve diarrhea and colitis symptoms.

Conditions

Clinical Stage 0 Cutaneous Melanoma AJCC v8; Clinical Stage I Cutaneous Melanoma AJCC v8; Clinical Stage IA Cutaneous Melanoma AJCC v8; Clinical Stage IB Cutaneous Melanoma AJCC v8; Clinical Stage II Cutaneous Melanoma AJCC v8; Clinical Stage IIA Cutaneous Melanoma AJCC v8; Clinical Stage IIB Cutaneous Melanoma AJCC v8; Clinical Stage IIC Cutaneous Melanoma AJCC v8; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Colitis; Lung Non-Small Cell Carcinoma; Malignant Genitourinary System Neoplasm; Malignant Solid Neoplasm; Pathologic Stage 0 Cutaneous Melanoma AJCC v8; Pathologic Stage I Cutaneous Melanoma AJCC v8; Pathologic Stage IA Cutaneous Melanoma AJCC v8; Pathologic Stage IB Cutaneous Melanoma AJCC v8; Pathologic Stage II Cutaneous Melanoma AJCC v8; Pathologic Stage IIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIC Cutaneous Melanoma AJCC v8; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Stage 0 Lung Cancer AJCC v8; Stage I Lung Cancer AJCC v8; Stage IA1 Lung Cancer AJCC v8; Stage IA2 Lung Cancer AJCC v8; Stage IA3 Lung Cancer AJCC v8; Stage IB Lung Cancer AJCC v8; Stage II Lung Cancer AJCC v8; Stage IIA Lung Cancer AJCC v8; Stage IIB Lung Cancer AJCC v8; Stage III Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Difference in stool microbiome pattern

  The primary endpoint is alpha diversity of bacteria species (measured using inverse Simpson index). It is a measure of diversity which takes into account the number of species present, as well as the relative abundance of each species. As species richness and evenness increase, so diversity increases.

  Up to 1 year

• Incidence of adverse events (AE) of fecal microbiota transplantation (FMT) (Project 3)

  Adverse events will be recorded by Common Terminology Criteria for Adverse Events version 5 as well as FMT-specific events. All events will be recorded with grade and attribution to FMT. Adverse events that are related to fecal microbiota transplantation will be summarized using frequency and percentage by AE grade, type and attributions.

  Up to 1 year

Secondary Outcomes (8)

• Immune profile factors associated with onset of ICPI-related colitis in blood and colon tissue

  Up to 1 year

• Genetic factors associated with onset of ICPI-related colitis in blood and colon tissue

  Up to 1 year

• Endoscopic and histologic features of ICPI-related colitis before and after medical treatment

  Baseline up to 1 year

• Changes of ICPI-related symptoms

  Up to 1 year

• Changes of quality of life (QoL)

  Up to 1 year

Study Arms (1)

Supportive Care (standard of care, sample collection, FMT)

EXPERIMENTAL

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: Best Practice; Other: Biospecimen Collection; Procedure: Endoscopic Procedure; Procedure: Fecal Microbiota Transplantation; Biological: Infliximab; Other: Laboratory Biomarker Analysis; Drug: Prednisone; Biological: Vedolizumab

Interventions

Endoscopic Procedure PROCEDURE

Undergo endoscopy

Also known as: Endoscopic Examination, Endoscopy

Supportive Care (standard of care, sample collection, FMT)

Best Practice OTHER

Receive standard of care

Also known as: standard of care, standard therapy

Supportive Care (standard of care, sample collection, FMT)

Biospecimen Collection OTHER

Undergo collection of stool, blood, and tissue samples

Supportive Care (standard of care, sample collection, FMT)

Fecal Microbiota Transplantation PROCEDURE

Undergo FMT

Also known as: Fecal Material Transplantation, Fecal Transplantation, FMT, Poo Transplant, Poop Transplant, Stool Transplant

Supportive Care (standard of care, sample collection, FMT)

Infliximab BIOLOGICAL

Given intravenously (IV)

Also known as: Avakine, cA2, Remicade, Remsima

Supportive Care (standard of care, sample collection, FMT)

Laboratory Biomarker Analysis OTHER

Ancillary studies

Supportive Care (standard of care, sample collection, FMT)

Prednisone DRUG

Given orally

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone

Supportive Care (standard of care, sample collection, FMT)

Vedolizumab BIOLOGICAL

Given IV

Also known as: Entyvio, Immunoglobulin G1, anti-(human integrin LPAM-1 (lymphocyte Peyer''s patch adhesion molecule 1)) (human-Mus musculus heavy chain), disulfide with human-Mus musculus kappa-chain, dimer, LDP 02, LDP-02, LDP02, MLN0002, MLN02

Supportive Care (standard of care, sample collection, FMT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of any stage melanoma, Non-Small Cell Lung Cancer or genitourinary (GU) malignancies (Project 1).
• Diagnosis of any cancer type (Projects 2 and 3)
• Treatment with any ICPI agent
• Ability to understand and willingness to sign an informed consent form and rate surveys
• Life expectancy \> 4 months (Project 3)
• ICPI-related diarrhea and/or 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 (project 1)
• 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)
• 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)
• 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

You may not qualify if:

• Age younger than 18 years
• History of inflammatory bowel disease, and/or radiation enteritis or colitis with active disease status at the time of study treatment initiation
• Pregnant and breastfeeding women
• 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
• Patients who develop concurrent non- GI toxicity at the time of FMT treatment (project 3)
• Patients with active bacterial or fungal infection (Project 3)
• Donors at risk for monkeypox infection and/ or exposure as determined by a questionnaire (Project 3)
• Withdrawal Criteria
• Patients may withdraw from the trial at any time
• Patients who develop GI perforation or toxic colitis that require surgery from ICPI colitis
• In project 3, if the first 30% of cases fail the fecal transplant treatment, then project 3 will be terminated

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Colitis; Carcinoma, Non-Small-Cell Lung; Urogenital Neoplasms; Lung Neoplasms

Interventions

Practice Guidelines as Topic; Standard of Care; Endoscopy; Fecal Microbiota Transplantation; Infliximab; CT-P13; Prednisone; deltacortene; prednylidene; vedolizumab; Immunoglobulin G; Disulfides; LDP-02

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Guidelines as Topic; Quality Assurance, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality Indicators, Health Care; Diagnostic Techniques, Surgical; Diagnostic Techniques and Procedures; Diagnosis; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Biological Therapy; Therapeutics; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Yinghong Wang

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Krishna Rajalu, MD

CONTACT

713-563-6086; kvaratharajalu@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2019
• First Posted: January 28, 2019
• Study Start: February 21, 2021
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

US (1)