Addition of Antibiotics to Upfront Treatment Regimen for Colorectal Cancer

Phase 2

Not yet recruiting

Interventions: Drug: Standard of Care Chemotherapy + Metronidazole, ciprofloxacin, aspirin

Brief Summary: 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).

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.

Recruitment & Eligibility

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

Exclusion Criteria

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 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)
Diagnosed with a malabsorptive syndrome
Inability to swallow tablets

Arm && Interventions

Group	Intervention	Description
Metronidazole Ciprofloxacin and Aspirin Therapy	Standard of Care Chemotherapy + Metronidazole, ciprofloxacin, aspirin	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Assess the tolerability of the study antibiotic regimen	Day 28 +/- 7 days	Total number of antibiotic doses over 28 days
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 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)

Locations (1): Virginia Commonwealth University
🇺🇸
Richmond, Virginia, United States