Adaptive, Individualized Dose Escalation of Fluorouracil-Based Chemotherapy for Gastrointestinal Cancer: Pilot Study of the FOX Regimen
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Proportion of patients that receive dose intensified infusional 5-FU in Cycle 6 of the FOX regimen
Study Overview
Brief Summary
This is a single-arm clinical trial to evaluate the feasibility of a chemotherapy regimen using adaptive, individualized dose escalation of 5-FU chemotherapy for patients who have good tolerance of the initial dose. Study participants will also receive oxaliplatin chemotherapy together with 5-FU, at standard doses. The goal of the study is to examine the feasibility and effectiveness of this approach, using individualized dose escalation of 5-FU in patients who do not have serious side effects at lower doses.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥ 18 years
- •Diagnosis of metastatic or locally advanced/inoperable colorectal cancer or non-colorectal gastrointestinal cancer (including cancers of the stomach, esophagus, appendix, small bowel, and ampulla)
- •Clinically appropriate staging imaging of the chest, abdomen, and pelvis performed within 30 days prior to registration
- •ECOG Performance Status: 0-1
Exclusion Criteria
- •Any prior receipt of oxaliplatin or fluoropyrimidine chemotherapy (other than radiation-sensitizing fluoropyrimidine chemotherapy)
- •Prior receipt of systemic chemotherapy in the 6 months prior to Day 1 of Cycle 1 of FOX (other than radiation-sensitizing chemotherapy)
- •Known mismatch repair deficiency or microsatellite instability-high disease
- •Known dihydropyrimidine dehydrogenase (DPD) deficiency, as identified by clinically indicated screening
- •Any confirmed second malignancy that is likely to require systemic therapy during the course of the six-month study period, in the opinion of the enrolling investigator
- •Any of the following baseline laboratory abnormalities:
- •Absolute neutrophil count (ANC) < 2,500/mm3
- •Platelet count < 100,000/mm3
- •Hemoglobin < 9 g/dL
- •Creatinine > 1.5 x ULN
- •Total bilirubin > 1.5 x ULN
- •AST/ALT > 5 x ULN
- •Patients who are unable to provide informed consent
- •Patients who are pregnant or breastfeeding
- •Patients who are incarcerated, homeless, or have active substance use disorders
Arms & Interventions
Study Arm
All patients in this single-study arm will be exposed to the FOX regimen, an adaptively dose-escalated chemotherapy regimen. The FOX regimen is comprised of oxaliplatin 85 mg/m2 IV on Day 1; leucovorin calcium 350 mg IV on Day 1; and infusional 5-FU IV over 46 hours (Days 1 and 2) - starting at a dose of 2,400 mg/m2 and adaptively adjusted toward a maximum dose of 3,200 mg/m2 over Cycles 2-4 using a clinical algorithm.
Intervention: FOX dose-escalation algorithm (Other)
Outcomes
Primary Outcomes
Proportion of patients that receive dose intensified infusional 5-FU in Cycle 6 of the FOX regimen
Time Frame: Through day 1 of Cycle 6 of FOX regimen (cycle length is 14 days)
The proportion of patients who receive dose-intensified infusional 5-FU (dosed at greater than or equal to 2,800 mg/m2) in Cycle 6 of the FOX regimen.
Secondary Outcomes
- Dose intensity of 5-FU and oxaliplatin(Through day 1 of Cycle 6 of FOX regimen (cycle length is 14 days))
- Mean plasma uracil concentration(Single treatment visit 0-30 days before Day 1 of Cycle 1 of FOX regimen, (cycle length is 14 days))
- Response rate to chemotherapy(Through 6 months from Cycle 1 Day 1 of FOX regimen)
- 5-FU drug exposure(Single treatment visit on Day 3 of treament Cycle 5 or Cycle 6 of FOX regimen, (cycle length is 14 days))
- Progression-free survival(Through 12 months from Cycle 1 Day 1 of FOX regimen)
Investigators
Gabriel A. Brooks
Associate Professor of Medicine
Dartmouth-Hitchcock Medical Center