Addition of Antibiotics to Upfront Treatment Regimen for Colorectal Cancer

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.

• Standard of Care Chemotherapy + Metronidazole, ciprofloxacin, aspirin (Drug): 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

Primary outcomes

• Best response by analysis using Response Evaluation Criteria in Solid Tumors [Up to 5 years]: 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.

Secondary outcomes

• 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. [Up to 5 years]: Evaluate the overall participant survival (OS) defined as the duration of time from diagnosis to date of death by any cause.
• 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 [Up to 5 years]: 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.
• Assess the tolerability of the study antibiotic regimen [Day 28 +/- 7 days]: Total number of antibiotic doses over 28 days
• Assess the tolerability of the study aspirin regimen for the duration of chemotherapy [Day 28 +/- 7 days]: Total number of aspirin doses over 28 days
• Evaluate the safety of MBMT in addition to a 5FU-based treatment regimen [Beginning of study procedures through day 28 Non-interventional arm), through day 90 (interventional arm)]: 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)

Sex: All, ages: 18 Years to any

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

• Emily Kinsey, MD, Principal investigator, Virginia Commonwealth University