A Phase II Trial Utilizing Metronidazole to Optimize the Microbiome of Rectal Adenocarcinoma Undergoing Neoadjuvant Therapy
Overview
- Phase
- Phase 2
- Intervention
- Standard of Care Neoadjuvant Therapy
- Conditions
- Rectal Adenocarcinoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Safety and adverse events (AEs)
- Status
- Recruiting
- Last Updated
- 16 days ago
Overview
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.
Detailed Description
* Primary Objectives Quantify the ability of a standard course of metronidazole to decrease populations of anaerobic bacteria from within rectal cancers in participants receiving neoadjuvant therapy. * Secondary Objectives To observe and record augmented anti-tumor activity of metronidazole in combination with standard of care therapies. Although the clinical benefit of \[this/these\] drug(s) has not yet been established, the intent of offering this treatment is to provide a possible therapeutic benefit, and thus the patient will be carefully monitored for tumor response in addition to safety and tolerability. As part of the therapeutic efficacy of metronidazole in combination with standard of care therapies, overall survival and recurrence free survival will be assessed among participants enrolled in the study over the two years following study completion. Quantify differential rates of pathologic response of tumors treated with metronidazole in combination with standard neoadjuvant therapy compared against historic controls. Those participants undergoing watch and wait protocols will not have the pathologic response and will not be included in the pathologic response assessment. Exploratory analysis of immune and microbial infiltrates between participant matched pre and post treatment tissues (when available). This will include bacterial taxal populations along with populations of various immune cell populations.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Standard of Care Neoadjuvant Therapy
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.
Standard of Care Neoadjuvant Therapy + Metronidazole
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.
Intervention: Metronidazole
Outcomes
Primary Outcomes
Safety and adverse events (AEs)
Time Frame: Through study completion; an average of 1 year.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0