Trial Utilizing Metronidazole to Optimize the Microbiome of Rectal Adenocarcinoma Undergoing Neoadjuvant Therapy

NCT06569368 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2023-0880NCI-2025-07395
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if adding metronidazole to standard therapy can decrease populations of Fusobacterium nucleatum (F. nucleatum) and other anaerobes (small organisms that cause infections) in participants with rectal cancer receiving neoadjuvant therapy, compared to neoadjuvant therapy alone.

Conditions

Rectal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year.

Study Arms (2)

Standard of Care Neoadjuvant Therapy + Metronidazole

EXPERIMENTAL

Participants found to be eligible to take part in this study, will be randomly assigned (as in the flip of a coin) to receive standard therapy alone or standard therapy plus metronidazole. Participants are assigned to the metronidazole group, will also take 1 tablet of metronidazole by mouth every 8 hours for 2 weeks.

Drug: Metronidazole

Standard of Care Neoadjuvant Therapy

NO INTERVENTION

Participants found to be eligible to take part in this study, will be randomly assigned (as in the flip of a coin) to receive standard therapy alone or standard therapy plus metronidazole. Participants in both study groups will receive their standard of care treatment, as assigned by their treating doctor outside of the research study.

Interventions

Metronidazole DRUG

Given by PO

Standard of Care Neoadjuvant Therapy + Metronidazole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with locally advanced rectal cancers (T3, T4, or N+ disease) with decision to treat with total neoadjuvant therapy.
• No previous cycles of cytotoxic chemotherapy in management of the index tumor.
• Age ≥18 years. Because of dosing differences between pediatric and adult populations and the introduced variability with these regiments to the study's primary outcomes, participants \<18 years of age, children are excluded from this study.
• ECOG performance status ≤2 (Karnofsky ≥60%,)
• Participants must have adequate organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/mcL platelets ≥100,000/mcL total bilirubin ≤ institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN creatinine ≤ institutional ULN
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Participants with unresectable distant metastases are ineligible.
• Participants with unresectable primary tumors are ineligible.
• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
• Postmenopausal (no menses in greater than or equal to 12 consecutive months).
• History of hysterectomy or bilateral salpingo-oophorectomy.
• Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 1 year prior to entering the study.
• Participants who are receiving any other investigational agents.
• Participants with brain metastases or other unresectable metastases who would therefore not undergo standard of care proctectomy.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to metronidazole or other agents used in study.
• Prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives.
• Concurrent treatment with disulfiram.
• Cockayne syndrome.
• Participants with uncontrolled intercurrent illness (Indicate clearly what type or extent).
• Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because metronidazole is a B2 agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with metronidazole, breastfeeding should be discontinued if the mother is treated with metronidazole. These potential risks may also apply to other agents used in this study.
• Participants who received cytotoxic chemotherapy within the last year are excluded from this study given known associations between chemotherapy administration and alterations in the tumoral microbiome.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Metronidazole

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michael G White, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael G White, MD

CONTACT

(713) 355-0897; mgwhite@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2024
• First Posted: August 26, 2024
• Study Start: July 10, 2024
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)