The Microbiome and Colorectal Cancer: Current Clinical Trials

Background: Colorectal cancer (CRC) is a leading cause of mortality in Western countries. It is the third most prevalent lethal cancer in the United States for both genders. Despite an overall decline, CRC is on the rise in young and middle-aged adults. Compared with people born in 1950, those born in 1990 have double the risk of colon cancer and are four times more likely to develop rectal cancer.[1] Long-term research points to genetic, environmental, and dietary factors as influential in the development, progression, and recurrence of CRC. More recent evidence suggests a correlation between intestinal microbiota composition and CRC, though no pattern of cause and effect has yet been identified.[2]

Researchers are exploring nutritional and other interventions to determine whether altering the gut microbiome can influence colorectal cancer. Following are several clinical trials in this discipline that are currently recruiting or will be recruiting in the near future.

SURVIVORS

Beans to Enrich the Gut Microbiome vs Obesity’s Negative Effects (BE GONE) Trial

ClinicalTrials.gov Identifier: NCT02843425 (Recruiting)

University of Texas MD Anderson Cancer Center, Houston, TX

Enrolling survivors with a previous history of colorectal cancer and MD Anderson patients who have had a precancerous colorectal polyp, and who have a current adult body mass index (BMI) of 25 or higher. This investigational study aims to determine whether eating canned, precooked beans can help improve the levels of healthy bacteria in the digestive system and reduce the effects of obesity on cancer risk.

Food and Microbiome Longitudinal Investigation (FAMiLI)

ClinicalTrials.gov Identifier: NCT03293758 (Recruiting)

New York University School of Medicine, New York, NY

Enrolling patients with a diagnosis of colon cancer. The study cohort is designed to improve understanding of the role of the human microbiome in health and disease.

Gut Microbiome in Fecal Samples from Patients with Metastatic Cancer Undergoing Chemotherapy or Immunotherapy

ClinicalTrials.gov Identifier: NCT02960282 (Recruiting)

University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA

Enrolling patients with metastatic disease. This trial focuses on studying the gut microbiome via fecal samples from patients with metastatic disease and who are undergoing chemotherapy or immunotherapy. Researchers seek to understand whether the make-up of the gut microbiome has a positive or negative influence on a patient’s response to these therapies.

Metabiomics Colon Cancer Clinical Research Study

ClinicalTrials.gov Identifier: NCT02151123 (Not yet recruiting)

University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO

Enrolling patients diagnosed with CRC. This clinical research aims to investigate the association of the gut microbiome with colonic neoplasia. Several types of gut microbiome samples will be collected from patients undergoing colectomy for colonic adenocarcinoma; these samples will be tested by the Metabiomics Colon Polyp and Colorectal Cancer Assay, and the percentage of false-negative results determined.

Metagenomic Evaluation of the Gut Microbiome in Patients with Lynch Syndrome and Other Hereditary Colonic Polyposis Syndromes

ClinicalTrials.gov Identifier: NCT02371135 (Recruiting)

Memorial Sloan Kettering Cancer Center, New York, NY

Enrolling patients with Lynch syndrome or other hereditary colonic polyposis syndromes. The study’s purpose is to understand the role that bacteria that normally live in the colon may play in colorectal cancer risk, in addition to the hereditary risk and potential dietary impact. Investigators will collect stool specimens, additional colon biopsy specimens, and questionnaire responses on diet and lifestyle.

Pilot Trial of Resistant Starch in Stage II–III Colorectal Cancer Survivors

ClinicalTrials.gov Identifier: NCT03781778 (Not Yet Recruiting)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Seattle, Washington

Enrolling patients diagnosed with stage II–III colorectal adenocarcinoma. This phase II pilot trial aims to understand the effect of resistant starch consumption on the gut microbiome and on biomarkers potentially related to colorectal cancer progression. A comparison will be made against consumption of foods made with corn starch.

HEALTHY VOLUNTEERS

Diet Modulation of Bacterial Sulfur and Bile Acid Metabolism and Colon Cancer Risk

ClinicalTrials.gov Identifier: NCT03550885 (Recruiting)

Rush University Medical Center|University of Illinois at Chicago, Chicago, IL

Enrolling adult African American women with a BMI 30 to < 50, 45–75 years of age, with elevated c-reactive protein and at increased risk for CRC. The study’s goal is to determine the extent to which a relationship between diet (independent variable) and mucosal markers of CRC risk can be explained by the abundance of sulfidogenic bacteria and hydrogen sulfide (H2S) concentrations &/or deoxycholic acid (DCA) and DCA-producing bacteria clostridium scindens (mediator variables).

Fiber to Reduce Colon Cancer I Alaska Native People

ClinicalTrials.gov Identifier: NCT03028831 (Recruiting)

Alaskan Native Tribal Health Consortium, Anchorage, AK

University of Pittsburgh, Pittsburgh, PA

Enrolling Alaska Native people (ANs), ages 40–65 years, with a BMI between 18–35. This double-blind, placebo-controlled study aims to determine whether, despite a high consumption of anti-inflammatory and antineoplastic n-3 fish oils, ANs are at increased risk of colon cancer because of colonic butyrate deficiency resulting from a remarkably low consumption of fiber-containing foods. Results will be used as the scientific basis for a definitive large-scale high-fiber supplementation study (to achieve > 50 g total fiber/d) to suppress adenomatous polyp recurrence following colonoscopy.

Omega-3 Fatty Acid for the Immune Modulation of Colon Cancer (OMICC)

ClinicalTrials.gov Identifier: NCT03661047 (Recruiting)

Harvard School of Public Health|Massachusetts General Hospital, Boston, MA

Enrolling those with confirmed or suspicion of adenocarcinoma, ages 18–75 years. This prospective, double-blind, placebo-controlled, stratified, randomized clinical trial will assess effects of daily 4-gram marine omega-3 polyunsaturated fatty acid (MO3PUFA), through treatment with AMR101 (VASCEPA, icosapent ethyl) on the tumor immune microenvironment and gut microbiome.

Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

References:

1. Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin. 2014;64:104–17.

2. Coleman OI, Nunes T. Role of the microbiota in colorectal cancer: updates on microbial associations and therapeutic implications. Biores Open Access. 2016;5:279-88.