Addition of Antibiotics to Upfront Treatment Regimen for Colorectal Cancer

Pilot Study Evaluating Microbiome Modulation Therapy (MBMT) With Ciprofloxacin, Metronidazole, and Aspirin in Addition to Standard of Care Chemotherapy in Patients Undergoing First-Line Therapy for Metastatic Colorectal Cancer

This is a 2-arm, noncomparative phase 2 trial designed to evaluate treatment outcomes with or without the addition of ciprofloxacin, metronidazole, and aspirin to first-line chemotherapy for patients with stage IV colorectal cancer (CRC).

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; CRC
• Intervention / Treatment: Drug: Standard of Care Chemotherapy + Metronidazole, ciprofloxacin, aspirin

Detailed Description

This is a pilot study to evaluate the efficacy and safety of chemotherapy with or without MBMT in patients with metastatic CRC. The primary objective is to evaluate the efficacy, as determined by the ORR, of fluorouracil (5FU) based treatment regimen with and without MBMT in patients with CRC.

• Study Type: Interventional
• Enrollment (Estimated): 97
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Massey IIT Research Operations; Phone Number: 804-628-6430; Email: masseyepd@vcu.edu

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University
      • Principal Investigator: Emily Kinsey, MD
      • Contact: Massey CTO GI Team; Phone Number: 804-628-6430; Email: masseygi@vcu.edu
    • Richmond, Virginia, United States, 23229
      • Not yet recruiting
      • Virginia Cancer Institute (VCI)
      • Principal Investigator: Purvi Shah, MD
      • Contact: Sue Moore, MSN, CNS; Phone Number: 1265 804-397-9640; Email: smoore@vacancer.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of stage IV colorectal cancer
• Measurable disease by Response evaluation criteria in solid tumors (RECIST) 1.1 criteria
• Planned first-line treatment with a 5FU-based doublet chemotherapy regimen for colon cancer, specifics of the regimen at the discretion of the treating physician Note: Patients who have received adjuvant therapy >6 months prior are eligible
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
• Absolute neutrophil count (ANC) ≥1,500 cells/μL
• Platelet count ≥100,000 cells/μL
• Hemoglobin ≥8 g/dL Note: The use of transfusion or other intervention to achieve hemoglobin ≥8 g/dL is acceptable.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) Note: Patients with documented liver metastases: AST and ALT ≤5 × ULN
• Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥40 mL/min using the Cockcroft-Gault equation: (140 - age) × body weight/plasma creatinine × 72 (× 0.85 if female)
• Radiographically measurable disease by RECIST 1.1
• Nonpregnant and not actively breastfeeding
• Sexually active patients of childbearing potential and their partners must agree to use medically acceptable form of contraception, per treating investigator, throughout the study Patients should continue to use medically acceptable methods of contraception after study treatment ends, following the guidance for their specific chemotherapy regimen.

Childbearing potential excludes:

Age > 50 years and naturally amenorrhoeic for > 1 year OR previous hysterectomy or bilateral salpingo-oophorectomy

• Patients on a pre-existing daily aspirin regimen may participate in the study without interrupting this regimen.
• Patients with a contraindication to aspirin may participate in the study. These patients will not be required to take aspirin as part of the study treatment.

Exclusion Criteria:

• Total colectomy
• Diagnosed with Cockayne Syndrome
• Using disulfiram, tizanidine, or theophylline and unable to stop taking these medications for the length of the microbiome modulation therapy
• On methotrexate doses of 15 mg/week or more
• History of allergic reaction to ciprofloxacin, metronidazole, or aspirin
• Fuss course of antibiotics in the 30 days before chemotherapy start Note: Full course is defined as ≥5 doses with an intent to treat a defined infection. Use of antibiotics intended for prophylaxis at the time of surgery is allowed
• Corrected QT interval (QTc) >480 on baseline ECG
• Diagnosed with a malabsorptive syndrome
• Inability to swallow tablets

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of care; First line chemotherapy as directed. Standard of care chemotherapy treatment options include but are not limited to the following: FOLFOX every 2 weeks; FOLFIRI every 2 weeks; FOLFOX + bevacizumab or panitumumab every 2 weeks; FOLFIRI + bevacizumab or panitumumab every 2 weeks; CAPEOX every 3 weeks; CAPEOX + bevacizumab or panitumumab every 3 weeks
Experimental: Metronidazole Ciprofloxacin and Aspirin Therapy; First line chemo therapy (standard of care) + Microbiome modulation therapy MBMT 500 mg metronidazole 3 times daily, 500 mg ciprofloxacin twice daily, and 81 mg aspirin once daily for 28 days	Drug: Standard of Care Chemotherapy + Metronidazole, ciprofloxacin, aspirin; Metronidazole, ciprofloxacin, aspirin is initiated Cycle 1 Day 1 of chemotherapy. May be initiated any time from 7 days before Cycle 1 Day 1 up to and including Cycle 1 Day 3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best response by analysis using Response Evaluation Criteria in Solid Tumors	Evaluate the objective response rate (ORR) of a fluorouracil (based) treatment regimen with or without the addition of MBMT in patients with colorectal cancer (CRC) by the number of participants that have a partial (PR) or complete response (CR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimate the overall survival (OS) of patients with colorectal cancer (CRC) treated with a 5FU-based treatment regimen with or without the addition of MBMT.	Evaluate the overall participant survival (OS) defined as the duration of time from diagnosis to date of death by any cause.	Up to 5 years
Estimate the progression free survival (PFS) of patients with CRC treated with a 5FU-based treatment regimen with or without the addition of the MBMT	Progression free survival (PFS) is defined as the duration of time from start of study 5FU-based treatment regimen to date of first progression or relapse.	Up to 5 years
Assess the tolerability of the study antibiotic regimen	Total number of antibiotic doses over 28 days	Day 28 +/- 7 days
Assess the tolerability of the study aspirin regimen for the duration of chemotherapy	Total number of aspirin doses over 28 days	Day 28 +/- 7 days
Evaluate the safety of MBMT in addition to a 5FU-based treatment regimen	The number of Adverse Events (AEs) captured using criteria in the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0)	Beginning of study procedures through day 28 Non-interventional arm), through day 90 (interventional arm)

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: American Cancer Society, Inc.
• Investigators: Principal Investigator: Emily Kinsey, MD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2025
• Primary Completion (Estimated): July 1, 2035
• Study Completion (Estimated): July 1, 2035

Study Registration Dates

• First Submitted: November 7, 2024
• First Submitted That Met QC Criteria: December 5, 2024
• First Posted (Actual): December 11, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Colorectal Cancer; CRC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Imidazoles; Phenols; Benzene Derivatives; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Nitroimidazoles; Nitro Compounds; Salicylates; Hydroxybenzoates; Aspirin; Metronidazole; Ciprofloxacin
• Other Study ID Numbers: MCC-23-20875; HM20031481 (Other Identifier: Virginia Commonwealth University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes