Pralatrexate in Combination With Oxaliplatin in Advanced Esophagogastric Cancer: A Phase II Trial With Predictive Molecular Correlates

Inclusion Criteria:

- Histologically confirmed carcinoma of the esophagus, stomach or gastro-esophageal
junction that is metastatic, or locally advanced and inoperable for cure;
histological sub-types permitted included adenocarcinoma, squamous-cell carcinoma, or
undifferentiated carcinoma (small-cell carcinoma variant is not eligible)

- No previous systemic therapy for metastatic or recurrent disease; therapy
(chemotherapy, radiotherapy, or both) administered in the neo-adjuvant, adjuvant, or
definitive setting for previously localized disease is permitted, provided it was
completed more than 6 months prior to enrollment; palliative radiotherapy is
permitted provided it is completed >= 3 weeks prior to study therapy initiation

- ECOG performance status 0-2

- Life expectancy >= 12 weeks

- Hemoglobin >= 9 g/dl

- Absolute neutrophil count >= 1500/mm^3

- Platelet count >= 100,000/mm^3

- Serum creatinine =< institutional upper limit normal (ULN)

- Bilirubin =< 1.5 x ULN

- Transaminases =< 3 x ULN; for documented liver metastases (transaminases up to 5 x
ULN is permitted)

- No evidence of >= grade 2 peripheral neuropathy

- Patients with reproductive potential must be willing to use an adequate contraceptive
method (e.g., abstinence, intrauterine device, oral contraceptives, barrier device
with spermicide or surgical sterilization) during treatment and for three months
after completing treatment; a negative pregnancy test is required for women of
child-bearing potential

- Written, informed consent

Exclusion Criteria:

- Hypersensitivity to platinum compounds

- Uncontrolled inter-current illness including but not limited to active infection,
symptomatic congestive heart failure, unstable angina, uncontrolled cardiac
arrhythmia, or psychiatric illness that would limit compliance with study
requirements

- Presence of brain metastases

- Patients with third-space (pleural, peritoneal) fluid not controllable with usual
drainage methods are not eligible

- History of second primary malignancy within 3 years prior to enrollment, except for
in-situ cervix carcinoma or non-melanoma skin cancer

- Undergone an allogeneic stem cell transplant

- Nursing women are ineligible