Individualized Dose Escalation of 5-FU for Gastrointestinal Cancer
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorDartmouth-Hitchcock Medical Center
About this trial
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
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Single group
Treatments tested in this trial
FOX dose-escalation algorithm
Other interventionChemotherapy dose-escalation algorithm based on the FOLFOX and FOLFOXIRI regimens
Treatment groups
36 Participants
are divided into 1 treatment groupGroup A: Study ArmExperimental treatment 1 intervention
Trial outcomes
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.
Time frame
Through day 1 of Cycle 6 of FOX regimen (cycle length is 14 days)Secondary outcomes
1
Response rate to chemotherapy
Response rate (stratified by colorectal cancer vs. gastroesophageal cancer) as defined using RECIST 1.1 imaging criteria
Time frame
Through 6 months from Cycle 1 Day 1 of FOX regimen2
Progression-free survival
Progression-free survival (PFS, stratified by colorectal cancer vs. gastroesophageal cancer, determined by retrospective review of medical records)
Time frame
Through 12 months from Cycle 1 Day 1 of FOX regimen3
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).
Time frame
Through day 1 of Cycle 6 of FOX regimen (cycle length is 14 days)4
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)
Time frame
Single treatment visit 0-30 days before Day 1 of Cycle 1 of FOX regimen, (cycle length is 14 days)Sponsors and contacts
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Source ClinicalTrials.gov