Clinical trial NCT05780684: Individualized Dose Escalation of 5-FU for Gastrointestinal Cancer
Official title: Adaptive, Individualized Dose Escalation of Fluorouracil-Based Chemotherapy for Gastrointestinal Cancer: Pilot Study of the FOX Regimen
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Colorectal Cancer
Esophagus Cancer
Appendix Cancer
Small Bowel Cancer
Ampullary Cancer
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
First posted: 2023-03-22
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients that receive dose intensified infusional 5-FU in Cycle 6 of the FOX regimen
timeFrame: Through day 1 of Cycle 6 of FOX regimen (cycle length is 14 days)
Secondary outcomes:
measure: Response rate to chemotherapy
timeFrame: Through 6 months from Cycle 1 Day 1 of FOX regimen
measure: Progression-free survival
timeFrame: Through 12 months from Cycle 1 Day 1 of FOX regimen
measure: Dose intensity of 5-FU and oxaliplatin
timeFrame: Through day 1 of Cycle 6 of FOX regimen (cycle length is 14 days)
measure: Mean plasma uracil concentration
timeFrame: Single treatment visit 0-30 days before Day 1 of Cycle 1 of FOX regimen, (cycle length is 14 days)
measure: 5-FU drug exposure
timeFrame: Single treatment visit on Day 3 of treament Cycle 5 or Cycle 6 of FOX regimen, (cycle length is 14 days)
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Gabriel A Brooks, M.D.
role: PRINCIPAL_INVESTIGATOR
References: