Clinical trial NCT03819296: Role of Gut Microbiome and Fecal Transplant on Medication-Induced GI Complications in Patients With Cancer
Official title: Role of Microbiome in the Realm of Immune-Checkpoint Inhibitor Induced GI Complications In Cancer Population
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2019-01-28
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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.

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

Primary outcomes:
measure: Difference in stool microbiome pattern
timeFrame: Up to 1 year
measure: Incidence of adverse events (AE) of fecal microbiota transplantation (FMT) (Project 3)
timeFrame: Up to 1 year
Secondary outcomes:
measure: Immune profile factors associated with onset of ICPI-related colitis in blood and colon tissue
timeFrame: Up to 1 year
measure: Genetic factors associated with onset of ICPI-related colitis in blood and colon tissue
timeFrame: Up to 1 year
measure: Endoscopic and histologic features of ICPI-related colitis before and after medical treatment
timeFrame: Baseline up to 1 year
measure: Changes of ICPI-related symptoms
timeFrame: Up to 1 year
measure: Changes of quality of life (QoL)
timeFrame: Up to 1 year
measure: Cytokine features that are associated with good response to FMT
timeFrame: Up to 1 year
measure: Genetic factors associated with onset of ICPI-related colitis in blood and colon tissue
timeFrame: Up to 1 year
measure: Changes of endoscopic and histologic features of ICPI-related colitis before and after fecal microbiota transplantation
timeFrame: Baseline up to 1 year
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Yinghong Wang
role: PRINCIPAL_INVESTIGATOR
References: