Personalized Therapy for Esophagogastric Cancer Using Thymidylate Synthase Genetic Markers

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 Exclusion Criteria

- Prior therapy for this cancer.

- A history of other malignancy ≤ 5 years previous with the exception of basal cell or
squamous cell carcinoma of the skin which were treated with local resection only or
carcinoma in situ of the cervix.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Known HIV-positivity on combination antiretroviral therapy because of the potential
for pharmacokinetic interactions with pemetrexed and/or oxaliplatin. In addition,
these patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.

Registration Exclusion Criteria

- Currently receiving any other investigational agents.

- Known brain metastases. Patients with known brain metastases must be excluded from
this clinical trial because of their poor prognosis and because they often develop
progressive neurologic dysfunction that would confound the evaluation of neurologic
and other adverse events.

- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to pemetrexed, 5-FU, leucovorin or oxaliplatin, or other agents
used for premedication in the study.

- Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 14
days of study entry.