Ciprofloxacin, Metronidazole, and Aspirin with Standard of Care Chemotherapy in Patients with Stage IV Colorectal Cancer Undergoing First-Line Therapy

Inclusion Criteria

• Age ≥ 18 years
• 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/uL
• Platelet count ≥ 100,000 cells/uL
• Hemoglobin ≥ 8 g/dL * Note: The use of transfusion or other intervention to achieve hemoglobin ≥ 8 g/dL is acceptable
• Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN * Note: Patients with documented liver metastases: AST and ALT ≤ 5 x ULN
• Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault equation
• Radiographically measurable disease by RECIST 1.1
• Non-pregnant 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

Exclusion Criteria

• Requires ongoing full dose anticoagulation * Note: Patients on full dose anticoagulation may be approached to discuss study participation if lowering anticoagulation dose is feasible per the discretion of the treating investigator. Patients will be required to lower the anticoagulation dose by half 48 hours before beginning study drugs
• 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
• Antibiotic use in the 30 days before chemotherapy start
• Corrected QT interval (QTc) > 480 on baseline electrocardiogram (ECG)
• Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 mL) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose of microbiome modulation therapy (significance determined by treating investigator)
• Inability to swallow tablets
• Diagnosed with a malabsorptive syndrome