Study of Erlotinib and Chemotherapy for Unresectable or Metastatic Cancer of the Esophagus and Gastric Cardia

A Phase II Study of Erlotinib and Modified FOLFOX-6 (5-Fluorouracil, Leucovorin and Oxaliplatin) in Previously Untreated Patients With Unresectable or Metastatic Adenocarcinoma of the Esophagus and Gastric Cardia

In this study, Erlotinib and 5-Fluorouracil (5-FU), Leucovorin and Oxaliplatin (a regimen known also as FOLFOX-6) will be the chemotherapy study drugs. The main purpose of this study is to test the safety and effectiveness of this combination of chemotherapy drugs and to see how they affect your cancer.

Another purpose of this study is to examine samples from your blood and tumor. This research will be done to better understand how subjects respond to treatment. Specifically, researchers will look at the way your genes and proteins respond to drugs like those used in this study.

Inclusion Criteria:

1. Metastatic or unresectable adenocarcinoma of the upper gastrointestinal tract that can be measured in at least one dimension according to RECIST criteria by CT or MRI

2. Gastric adenocarcinomas may be included if the primary tumor arises within 5 cm of the anatomic gastro-esophageal junction (distal esophagus) or from the gastric cardia as indicated by either endoscope or imaging.

3. Previously untreated with chemotherapeutic agents for unresectable or metastatic disease.

4. Adjuvant chemotherapy and/or radiotherapy are allowed as long as no oxaliplatin was used in the past 12 months.

5. ECOG performance status 0 or 1

6. Age > 18 years old.

7. Life expectancy greater than 6 months.

8. Peripheral neuropathy: must be < grade 1

9. Absolute neutrophil count > 1,500/mm3

10. Hemoglobin > 9.0 g/dl

11. Platelet count > 100,000/mm3

12. Hepatic Function:

    1. Total Bilirubin < or = to 1.5 x ULN
    2. AST and ALT must be < or = to 3.0 x ULN (< or = to 5.0 x ULN if there is liver metastasis).

13. Creatinine clearance of > 60 ml/min as calculated by the Cockcroft Gault formula. (Ccr = ((140-Age) X Wt (kg))/ (72 X SCr (mg/100ml) for males).

    (Ccr = ((140-Age) X Wt (kg))/ (72 X SCr (mg/100ml) x 0.85 for females)

14. Women of childbearing potential must have a negative pregnancy test by urine or serum testing.

15. Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 4 months after the last treatment.

16. Patients must have signed IRB approved informed consent

17. Patients must have the ability to comply with study and follow-up procedures.

Exclusion Criteria:

1. Patients with known hypersensitivity to any components of oxaliplatin, leucovorin, 5-fluorouracil (or other fluoropyrimidines) or erlotinib.
2. Women who are breast-feeding or pregnant.
3. Presence of > Grade 2 neuropathy
4. Patients with prior malignancy other than non-melanoma skin cancer or cervical carcinoma in situ within the past five years
5. Current or prior history of central nervous system or brain metastases
6. Any other medical conditions, which, in the opinion of the investigator, would preclude subjects to participate in the study.
7. Patients who have received chemotherapy, surgery or radiation therapy within 30 days prior to the first dose.
8. INR greater than 3.5 for patients on warfarin
9. Known HIV infection