Individualized Dose Escalation of 5-FU for Gastrointestinal Cancer

NCT05780684 | Recruiting DMC

• 2 other identifiers: STUDY0200187322BRO873
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer; Esophagus Cancer; Appendix Cancer; Small Bowel Cancer; Ampullary Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Response rate to chemotherapy

  Through 6 months from Cycle 1 Day 1 of FOX regimen

• Progression-free survival

  Through 12 months from Cycle 1 Day 1 of FOX regimen

• 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)

• 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)

Study Arms (1)

Study Arm

EXPERIMENTAL

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.

Other: FOX dose-escalation algorithm

Interventions

FOX dose-escalation algorithm OTHER

Chemotherapy dose-escalation algorithm based on the FOLFOX and FOLFOXIRI regimens

Study Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Esophageal Neoplasms; Appendiceal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Cecal Neoplasms; Cecal Diseases

Study Officials

• Gabriel A Brooks, M.D.

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Research Nurse

CONTACT

603-653-3637; cancer.research.nurse@hitchcock.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: March 10, 2023
• First Posted: March 22, 2023
• Study Start: July 14, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)