Ampullary Cancer, Appendix Cancer, Colorectal Cancer, Esophagus Cancer, Small Bowel Cancer
Conditions
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.
Interventions
OTHERFOX dose-escalation algorithm
Chemotherapy dose-escalation algorithm based on the FOLFOX and FOLFOXIRI regimens
Sponsors
Dartmouth-Hitchcock Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
CONTACTResearch Nurse
PRINCIPAL_INVESTIGATORGabriel A Brooks, M.D.
Dartmouth-Hitchcock Medical Center
Outcome results
None listed