Individualized Dose Escalation of 5-FU for Gastrointestinal Cancer

Dartmouth Health

Status: Enrolling

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

Treatments: Other: FOX dose-escalation algorithm

Study type: Interventional

Funder types: Other

Identifiers

NCT05780684

STUDY02001873

22BRO873 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 36 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

36 participants in 1 patient group

Study Arm

Experimental group

Description:

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.

Treatment:

Other: FOX dose-escalation algorithm