Individualized Dose Escalation of 5-FU for Gastrointestinal Cancer

Not Applicable

Recruiting

• Conditions: Esophagus Cancer; Appendix Cancer; Small Bowel Cancer; Colorectal Cancer; Ampullary Cancer
• Interventions: Other: FOX dose-escalation algorithm

• Registration Number: NCT05780684
• Lead Sponsor: Dartmouth-Hitchcock Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-03-10
• Study First Submitted QC: 2023-03-10
• Study First Posted: 2023-03-22
• Study Start: 2023-07-14
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-29
• Last Update Posted: 2024-07-31
• Primary Completion: 2025-11
• Study Completion: 2026-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Study Arm	FOX dose-escalation algorithm	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.

Primary Outcome Measures

Name	Time	Method
Proportion of patients that receive dose intensified infusional 5-FU in Cycle 6 of the FOX regimen	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 Outcome Measures

Name	Time	Method
Mean plasma uracil concentration	Single treatment visit 0-30 days before Day 1 of Cycle 1 of FOX regimen, (cycle length is 14 days)	Difference in mean plasma uracil concentration between patients who did and did not achieve sustained 5-FU dose escalation to ≥ 2,800 mg/m2 (primary endpoint)
Response rate to chemotherapy	Through 6 months from Cycle 1 Day 1 of FOX regimen	Response rate (stratified by colorectal cancer vs. gastroesophageal cancer) as defined using RECIST 1.1 imaging criteria
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)	5-FU drug exposure, measured as the area under the drug concentration curve (AUC). AUC will be calculated by multiplying the measured 5-FU concentration at steady state by the 5-FU infusion duration in hours.
Dose intensity of 5-FU and oxaliplatin	Through day 1 of Cycle 6 of FOX regimen (cycle length is 14 days)	Dose intensity of 5-FU and oxaliplatin over Cycles 1-6. Dose intensity will be calculated separately for each component of the FOLFOX regimen (5-FU infusion and oxaliplatin).
Progression-free survival	Through 12 months from Cycle 1 Day 1 of FOX regimen	Progression-free survival (PFS, stratified by colorectal cancer vs. gastroesophageal cancer, determined by retrospective review of medical records)

Trial Locations

Locations (1)

Dartmouth-Hitchcock Medical Center; 🇺🇸 Lebanon, New Hampshire, United States