Microbiotic Product to Promote Microbiome Health and Improve Chemotherapy Delivery

Stage IV Colon Cancer AJCC v8 Clinical Trial

Official title:

A Randomized Trial of Microbiotic Product (NBT-NM108) to Promote Microbiome Health and Improve Chemotherapy Delivery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05296681
• Other study ID #: 072201
• Secondary ID: Pro2022000222
• Status: Recruiting
• Phase: Phase 2
• Start date: May 3, 2022
• Est. completion date: July 1, 2025

Study information

• Verified date: March 2024
• Source: Rutgers, The State University of New Jersey
• Contact: Howard S Hochster, MD
• Phone: 732-235-2465
• Email: howard.hochster[@]rutgers.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: July 1, 2025
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colonic Neoplasms
• 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

Intervention

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

Locations

Country	Name	City	State
United States	Robert Wood Johnson University Hospital, Hamilton	Hamilton	New Jersey
United States	Monmouth Medical Center	Lakewood	New Jersey
United States	RWJBarnabas Health - Monmouth Medical Center Southern Campus	Lakewood	New Jersey
United States	Cooperman Barnabas Medical Center	Livingston	New Jersey
United States	Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	The Cancer Center	Newark	New Jersey
United States	Robert Wood Johnson University Hospital, Somerset	Somerville	New Jersey
United States	Community Medical Center	Toms River	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Howard S. Hochster, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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. Dose reduction should occur for CTCAE grade 3 or higher toxicity given maximum antidiarrheal support with Imodium and/or Lomotil.	Eight weeks
Primary	Tumor Response by RECIST v1.1 Criteria	Response and progression will be evaluated in this study using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used for tumor measurements	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