Individualized Dose Escalation of 5-FU for Gastrointestinal Cancer

Colorectal Cancer Clinical Trial

Official title:

Adaptive, Individualized Dose Escalation of Fluorouracil-Based Chemotherapy for Gastrointestinal Cancer: Pilot Study of the FOX Regimen

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05780684
• Other study ID #: STUDY02001873
• Secondary ID: 22BRO873
• Status: Recruiting
• Phase: N/A
• Start date: July 14, 2023
• Est. completion date: May 2026

Study information

• Verified date: July 2023
• Source: Dartmouth-Hitchcock Medical Center
• Contact: Casey O'Quinn, M.S.
• Phone: 603-653-9338
• Email: Casey.M.O'Quinn[@]hitchcock.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single-arm clinical trial that will evaluate the feasibility of a chemotherapy regimen 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: May 2026
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ampullary Cancer
• Appendiceal Neoplasms
• Appendix Cancer
• Colorectal Cancer
• Esophageal Neoplasms
• Esophagus Cancer
• Gastrointestinal Neoplasms
• Small Bowel Cancer

Intervention

Other:
• FOX dose-escalation algorithm
Chemotherapy dose-escalation algorithm based on the FOLFOX and FOLFOXIRI regimens

Locations

Country	Name	City	State
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
Dartmouth-Hitchcock Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients that receive dose intensified infusional 5-FU in Cycle 6 of the FOX regimen	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.	Through day 1 of Cycle 6 of FOX regimen (cycle length is 14 days)
Secondary	Response rate to chemotherapy	Response rate (stratified by colorectal cancer vs. gastroesophageal cancer) as defined using RECIST 1.1 imaging criteria	Through 6 months from Cycle 1 Day 1 of FOX regimen
Secondary	Progression-free survival	Progression-free survival (PFS, stratified by colorectal cancer vs. gastroesophageal cancer, determined by retrospective review of medical records)	Through 12 months from Cycle 1 Day 1 of FOX regimen
Secondary	Dose intensity of 5-FU and oxaliplatin	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).	Through day 1 of Cycle 6 of FOX regimen (cycle length is 14 days)
Secondary	Mean plasma uracil concentration	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)	Single treatment visit 0-30 days before Day 1 of Cycle 1 of FOX regimen, (cycle length is 14 days)
Secondary	5-FU drug exposure	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.	Single treatment visit on Day 3 of treament Cycle 5 or Cycle 6 of FOX regimen, (cycle length is 14 days)