Addition of Antibiotics to Upfront Treatment Regimen for Colorectal Cancer

Official title

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

Overview

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.

Interventions

• 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

Primary outcome measures

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

Secondary outcome measures (5)

• 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. [Time frame: 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 [Time frame: Up to 5 years]
• Assess the tolerability of the study antibiotic regimen [Time frame: Day 28 +/- 7 days]
• Assess the tolerability of the study aspirin regimen for the duration of chemotherapy [Time frame: Day 28 +/- 7 days]
• Evaluate the safety of MBMT in addition to a 5FU-based treatment regimen [Time frame: Beginning of study procedures through day 28 Non-interventional arm), through day 90 (interventional arm)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• Virginia Cancer Institute (VCI) — Richmond
• Virginia Commonwealth University — Richmond

Identifiers

NCT: NCT06728072 · MCC-23-20875 · HM20031481

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗