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

Overview

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.

Interventions

• Drug NBT-NM108
  Patients receive irinotecan-based chemotherapy per standard of care.

Primary outcome measures

• 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 [Time frame: Eight weeks]
• Tumor Response by RECIST v1.1 Criteria [Time frame: 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]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 10 centers

• Robert Wood Johnson University Hospital, Hamilton — Hamilton
• Monmouth Medical Center — Lakewood
• RWJBarnabas Health - Monmouth Medical Center Southern Campus — Lakewood
• Cooperman Barnabas Medical Center — Livingston
• Robert Wood Johnson University Hospital — New Brunswick
• Rutgers Cancer Institute of New Jersey — New Brunswick
• The Cancer Center — Newark
• Newark Beth Israel Medical Center — Newark
• … and 2 more centers

Identifiers

NCT: NCT05296681 · 072201 · Pro2022000222

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗