Individualized Dose Escalation of 5-FU for Gastrointestinal Cancer
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Study Arm 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
Chemotherapy dose-escalation algorithm based on the FOLFOX and FOLFOXIRI regimens
|
Outcome Measures
Primary Outcome Measures
- Proportion of patients that receive dose intensified infusional 5-FU in Cycle 6 of the FOX regimen [Through day 1 of Cycle 6 of FOX regimen (cycle length is 14 days)]
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.
Secondary Outcome Measures
- Response rate to chemotherapy [Through 6 months from Cycle 1 Day 1 of FOX regimen]
Response rate (stratified by colorectal cancer vs. gastroesophageal cancer) as defined using RECIST 1.1 imaging criteria
- Progression-free survival [Through 12 months from Cycle 1 Day 1 of FOX regimen]
Progression-free survival (PFS, stratified by colorectal cancer vs. gastroesophageal cancer, determined by retrospective review of medical records)
- Dose intensity of 5-FU and oxaliplatin [Through day 1 of Cycle 6 of FOX regimen (cycle length is 14 days)]
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).
- Mean plasma uracil concentration [Single treatment visit 0-30 days before Day 1 of Cycle 1 of FOX regimen, (cycle length is 14 days)]
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)
- 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)]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 18 years
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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)
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Clinically appropriate staging imaging of the chest, abdomen, and pelvis performed within 30 days prior to registration
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ECOG Performance Status: 0-1
Exclusion Criteria:
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Any prior receipt of oxaliplatin or fluoropyrimidine chemotherapy (other than radiation-sensitizing fluoropyrimidine chemotherapy)
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Prior receipt of systemic chemotherapy in the 6 months prior to Day 1 of Cycle 1 of FOX (other than radiation-sensitizing chemotherapy)
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Known mismatch repair deficiency or microsatellite instability-high disease
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Known dihydropyrimidine dehydrogenase (DPD) deficiency, as identified by clinically indicated screening
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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
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Any of the following baseline laboratory abnormalities:
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Absolute neutrophil count (ANC) < 2,500/mm3
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Platelet count < 100,000/mm3
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Hemoglobin < 9 g/dL
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Creatinine > 1.5 x ULN
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Total bilirubin > 1.5 x ULN
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AST/ALT > 5 x ULN
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Patients who are unable to provide informed consent
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Patients who are pregnant or breastfeeding
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Patients who are incarcerated, homeless, or have active substance use disorders
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Dartmouth-Hitchcock Medical Center
Investigators
- Principal Investigator: Gabriel A Brooks, M.D., Dartmouth-Hitchcock Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STUDY02001873
- 22BRO873