Study of Erlotinib and Chemotherapy for Unresectable or Metastatic Cancer of the Esophagus and Gastric Cardia
Condition: Unresectable Adenocarcinoma of the Esophagus; Metastatic Adenocarcinoma of the Esophagus; Unresectable Adenocarcinoma of Gastric Cardia; Metastatic Adenocarcinoma of Gastric Cardia
MeSH terms: Adenocarcinoma; Esophageal Neoplasms
Intervention: FOLFOX; 5-FU; Erlotinib
Intervention description: Once every two weeks all patients will receive Oxaliplatin 85 mg/m2 IV, Leucovorin 400 mg/m2 IV and 5-FU 400 mg/m2 IV infusions; 5-FU 2400 mg/m2 IV will be given via pump for 46-48 hours at home.; All patients will also be given Erlotinib, 100 mg orally daily for the first 4 weeks. Those patients who have not experienced toxicities will increase the dose level to 150 mg daily. Patients who have toxicities will remain at the 100 mg dose level or lower if necessary.
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin; Erlotinib Hydrochloride; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Unresectable; Metastatic; Esophagus; Gastric Cardia

Summary:

      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.
    

Eligibility criteria:

        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