Melanoma Clinical Trial

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

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.

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Full 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.

III. To assess the safety and tolerability and efficacy of fecal microbiota transplantation (FMT).

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 document the changes of ICPI-related symptoms and the impact on functioning and quality of life (QoL) from fecal microbiota transplantation by patient-reported outcomes (PRO).

V. To assess stool microbiome and cytokine features that are associated with good response to fecal microbiota transplantation.

VI. To assess the factors in genetic/immune profile obtained from blood and colon tissue that are associated with good response to fecal microbiota transplantation.

VII. To characterize the endoscopic and histologic features of ICPI-related colitis before and after 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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

PROJECT 1 AND 2: Diagnosis of any stage melanoma, non-small cell lung cancer or genitourinary (GU) malignancies
PROJECT 3: Diagnosis of any cancer type
Treatment with any ICPI agent
Ability to understand and willingness to sign an informed consent form and rate on surveys
Life expectancy > 4 months
PROJECT 1: 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
PROJECTS 2 AND 3: ICPI-related colitis and/or diarrhea of peak grade 2 or above as GI toxicity without involvement of non-GI toxicity within 45 days prior to (i) initiation of observational study treatment and (ii) FMT

PROJECT 3: ICPI-related colitis and/or diarrhea of peak grade 2 or above within 45 days prior to FMT with ANY of the following characteristics:

refractory to treatment of steroid and two doses of non-steroidal immunosuppressants e.g. infliximab and/or vedolizumab
contraindication for immunosuppressive treatment
recurrence after successful initial treatment
recurrent symptoms once steroid is tapered down/off or diarrhea/colitis symptoms are steroid dependent, or
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
PROJECT 2 AND 3: 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 2 AND 3: 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 Bacillus Calmette-Guerin (BCG) inoculation, chronic colonization) prior to initiation of diarrhea/colitis treatment

Exclusion Criteria:

Positive GI infection at the onset of ICPI-related GI toxicity
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
PROJECT 2: Patients who have a contraindication for immunosuppressive treatment
PROJECT 3: Patients who develop concurrent or non-GI toxicity at the time of FMT treatment
PROJECT 2 and 3: Patients with active bacterial or fungal infection

Study is for people with:

Melanoma

Phase:

Phase 1

Estimated Enrollment:

800

Study ID:

NCT03819296

Recruitment Status:

Recruiting

Sponsor:

M.D. Anderson Cancer Center

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There is 1 Location for this study

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M D Anderson Cancer Center
Houston Texas, 77030, United States More Info
Yinghong Wang
Contact
713-563-4382
[email protected]
Yinghong Wang
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Melanoma

Phase:

Phase 1

Estimated Enrollment:

800

Study ID:

NCT03819296

Recruitment Status:

Recruiting

Sponsor:


M.D. Anderson Cancer Center

How clear is this clinincal trial information?

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