Addition of Antibiotics to Upfront Treatment Regimen for Colorectal Cancer

Inclusion Criteria:

• Diagnosis of stage IV colorectal cancer

• Measurable disease by Response evaluation criteria in solid tumors (RECIST) 1.1criteria

• Planned first-line treatment with a 5FU-based doublet chemotherapy regimen for coloncancer, 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 achievehemoglobin ≥8 g/dL is acceptable.

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upperlimit 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 theCockcroft-Gault equation: (140 - age) × body weight/plasma creatinine × 72 (× 0.85if female)

• Radiographically measurable disease by RECIST 1.1

• Nonpregnant and not actively breastfeeding

• Sexually active patients of childbearing potential and their partners must agree touse medically acceptable form of contraception, per treating investigator,throughout the study Patients should continue to use medically acceptable methods ofcontraception after study treatment ends, following the guidance for their specificchemotherapy regimen.

Childbearing potential excludes:

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

Exclusion Criteria:

• ongoing full dose anticoagulation Note: Patients on full dose anticoagulation may beapproached to discuss study participation if lowering anticoagulation dose isfeasible per the discretion of the treating investigator. Patients will be requiredto 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 thesemedications 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 Note: Use of antibioticsintended for prophylaxis at the time of surgery is allowed

• Corrected QT interval (QTc) >480 on baseline ECG

• Clinically significant hematuria, hematemesis, or hemoptysis of >0.5 teaspoon (2.5mL) of red blood, or other history of significant bleeding (eg, pulmonaryhemorrhage) within 12 weeks before first dose of microbiome modulation therapy (significance determined by treating investigator)

• Diagnosed with a malabsorptive syndrome

• Inability to swallow tablets