Esophagogastric Cancer
Conditions
Brief summary
In this study the investigators aim to: 1) confirm the objective response rate (ORR) observed in the investigators initial study for patients with the TSER\*2/\*2 genotype 2) determine whether PEMOX regimen is more worthy of future development for this patient genotype selected population than FOLFOX based on the data indicating that pemetrexed may be a better TS targeted agent than 5-FU. Patients who are homozygous for the TSER\*2 allele (TSER\*2/\*2) will be able to continue in the study and will be randomized. Patients with other TSER genotypes will not be included and will be considered screen fails. The first 8 patients with the TSER\*2/\*2 genotype will be randomized 1:1 to receive treatment with either PEMOX or FOLFOX (4 in each group). Analysis of the objective response rate (ORR) in each treatment arm will occur after the first 8 patients are enrolled. Using the proposed Bayesian design, subsequent patients will be preferentially assigned to the better performing treatment arm based on continuous real-time reassessments of ORR results.
Interventions
DRUGPemetrexed
DRUGOxaliplatin
DRUGLeucovorin
DRUGFluorouracil
GENETICGermline genotyping analyses for TSER
Sponsors
Gateway for Cancer Research
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Pre-Registration Inclusion Criteria * Histologically or cytologically confirmed unresectable or metastatic esophagogastric adenocarcinoma. * Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>10 mm with CT scan, as \>20 mm by chest x-ray, or \>10 mm with calipers by clinical exam. PET/CT scan is acceptable as a substitute for a CT scan if the CT portion of the PET/CT is of identical diagnostic quality to a diagnostic CT scan. * At least 18 years of age. * ECOG performance status \< 2 * Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable). Registration Inclusion Criteria * TSER genotype \*2/\*2 * ECOG performance status \< 2 * Normal bone marrow and organ function as defined below: * Absolute neutrophil count ≥ 1,500 cells/mm3 * Platelets ≥ 100,000 cells/mm3 * Total bilirubin \< 1.5 x IULN * AST(SGOT)/ALT(SGPT) \< 3.0 x IULN * Creatinine within normal institutional limits OR Creatinine clearance ≥ 45 mL/min/1.73 m2 for patients with creatinine levels above institutional normal * Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
Exclusion criteria
Pre-Registration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Baseline, end of every 4th cycle, and end of treatment (estimated average of 6 months) | ORR=complete response + partial response by RECIST criteria Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Every 3 months for up to 4 years from the date of study registration or until death, whichever occurs first | OS = The length of time from the start of treatment to time of death. |
| Quality of life | Baseline and Day 1 of each cycle through Cycle 5 Day 1 (approximately Day 70) | Quality of life will be assessed by the EORTC QLQ-C30 and the EORTC QLQ-STO22 |
Outcome results
None listed