Clinical trial NCT06728072: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colorectal Cancer
CRC
Keywords: Colorectal Cancer
CRC
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: American Cancer Society, Inc.
First posted: 2024-12-11
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

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 Note: Use of antibiotics intended 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 (2.5 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

Primary outcomes:
measure: Best response by analysis using Response Evaluation Criteria in Solid Tumors
timeFrame: Up to 5 years
Secondary outcomes:
measure: 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.
timeFrame: Up to 5 years
measure: 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
timeFrame: Up to 5 years
measure: Assess the tolerability of the study antibiotic regimen
timeFrame: Day 28 +/- 7 days
measure: Assess the tolerability of the study aspirin regimen for the duration of chemotherapy
timeFrame: Day 28 +/- 7 days
measure: Evaluate the safety of MBMT in addition to a 5FU-based treatment regimen
timeFrame: Beginning of study procedures through day 28 Non-interventional arm), through day 90 (interventional arm)
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Emily Kinsey, MD
role: PRINCIPAL_INVESTIGATOR
References: