Clinical trial NCT05296681: Microbiotic Product to Promote Microbiome Health and Improve Chemotherapy Delivery
Official title: A Randomized Trial of Microbiotic Product (NBT-NM108) to Promote Microbiome Health and Improve Chemotherapy Delivery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Colon Carcinoma
Stage IV Colon Cancer AJCC v8
Stage IVA Colon Cancer AJCC v8
Stage IVB Colon Cancer AJCC v8
Stage IVC Colon Cancer AJCC v8
Keywords: chemotherapy-induced diarrhea
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
First posted: 2022-03-25
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be assigned to receive NBT-NM108 or no microbiome support in a 2:1 ratio
Primary purpose: TREATMENT

Brief summary: This phase II trial tests whether NBT-NM108 works in reducing chemotherapy-induced diarrhea in patients with colon cancer that has spread to other places in the body (metastatic). Irinotecan is one of the most used medicine for colon cancer, but it leads to diarrhea in most patients receiving it and among some of them, severe diarrhea can occur. NBT-NM108 is a high dietary fiber formula that is developed based on research findings that have shown that high fiber diets can help maintain healthy bacteria in the gut and improve gut function. Giving NBT-NM108 to patients with colon cancer receiving chemotherapy may help relieve or lessen diarrhea symptoms and lead to improved tolerance of the chemotherapy drug, irinotecan.

Detailed description: PRIMARY ENDPOINT:

Dose Intensity of Irinotecan administered (mg/m2/week)

SECONDARY ENDPOINTS:

1. Reduction in % Patients Needing Dose Modification for Diarrhea
2. Toxicity Grade of diarrhea
3. Response Rate
4. Time to Progression-free survival

EXPLORATORY ENDPOINTS:

1. 16S rRNA gene sequencing to reveal changes of the gut microbiota including institution of foundation guilds and restoration of healthy microbiome
2. Short chain fatty acids analysis (promotion of acetic and butyric acid production)
3. Markers for gut inflammation such as fecal lipocalin 2
4. Gut barrier function test to see if the restoration of healthier gut microbiota would improve gut barrier function.

Eligibility criteria: Inclusion Criteria

* Biopsy proven and metastatic colon cancer
* Candidate for Second-line or later line therapy with irinotecan-based chemotherapy regimen with starting dose of irinotecan at 180 mg/m2 q2w.

Participants who have had prior irinotecan will be eligible if they are off irinotecan for at least three months and stools have returned to baseline consistency.

* Performance Status (PS) 0-1
* Lab values as acceptable for trials: Absolute Neutrophil Count( ANC) \>1500/uL; Creatinine \< 1.5 x Upper Limit of Normal (ULN); Transaminases \< 5x ULN; Bilirubin \< 1.5 x ULN; Albumin \> 3.0 g/dL
* No known UGTA1A\* genotype

Exclusion Criteria

* Grade two diarrhea or greater (4-6 movements per day over baseline)
* Inability to take oral supplements
* Current antibiotic therapy
* Baseline grade 3-4 diarrhea Participants with grade two diarrhea should undergo stool evaluation with stool test for bacteria (Salmonella, Shigella, Campylobacter, Yersinia Mycobacterium), bacterial toxin (Clostridium difficile), ova and parasites (Giardia, Entamoeba, Isospora, Cyclospora, Cryptosporidium, Microsporidium), or viruses (Cytomegalovirus), associated with an ongoing active infection and diarrhea. They will be eligible if this evaluation shows no infection.
* History of the following infections and/or disease which could lead to diarrhea:
* History of prior positive gastrointestinal biopsy, gastrointestinal culture, or stool test for bacteria (Salmonella, Shigella, Campylobacter, Yersinia, Mycobacterium), bacterial toxin (Clostridium difficile), ova and parasites (Giardia, Entamoeba, Isospora, Cyclospora, Cryptosporidium, Microsporidium), or viruses (Cytomegalovirus), associated with an ongoing active infection and diarrhea unless fully treated with at least three months normal stool.
* History of ulcerative colitis, Crohn's disease, celiac sprue (gluten-enteropathy), chronic pancreatitis, malabsorption, or any other gastrointestinal disease associated with diarrhea.

Primary outcomes:
measure: The number of participants with treatment-related Adverse Events as Assessed by Cancer Therapy Evaluation Program Common Toxicity Criteria (CTCAE) Version 5.0 for toxicity and Adverse Event reporting
timeFrame: Eight weeks
measure: Tumor Response by RECIST v1.1 Criteria
timeFrame: Imaging for response assessment will be obtained before the initiation of conditioning (no more than 4 weeks prior to apheresis) and at the 6-week follow up time point
Secondary outcomes:
Other outcomes:
Locations:
city: Hamilton
country: United States
facility: Robert Wood Johnson University Hospital, Hamilton
state: New Jersey
city: Lakewood
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Lakewood
country: United States
facility: RWJBarnabas Health - Monmouth Medical Center Southern Campus
state: New Jersey
city: Livingston
country: United States
facility: Cooperman Barnabas Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Newark
country: United States
facility: The Cancer Center
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Somerville
country: United States
facility: Robert Wood Johnson University Hospital, Somerset
state: New Jersey
city: Toms River
country: United States
facility: Community Medical Center
state: New Jersey
Study officials:
affiliation: Rutgers University
name: Howard S Hochster, MD
role: PRINCIPAL_INVESTIGATOR
References: