Taxotere, Cisplatin and Irinotecan (CPT-11) for Esophagogastric Cancer

• To assess the duration of response and overall survival of patients with esophageal or gastric carcinoma to weekly Taxotere, Cisplatin, and Irinotecan. [ Time Frame: TBD ] [ Designated as safety issue: No ]
• To assess the toxicity of this combination in esophageal or gastric carcinoma. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

• To assess the duration of response and overall survival of patients with esophageal or gastric carcinoma to weekly Taxotere, Cisplatin, and Irinotecan.
• To assess the toxicity of this combination in esophageal or gastric carcinoma.

This is a phase II study of taxotere, cisplatin and irinotecan (CPT-11) used in combination to treat metastatic esophageal and gastric cancer in an effort to see what effects (good and bad) the combination may have on the patients cancer.

• Taxotere, cisplatin and irinotecan will be administered to the patient once weekly for 2 weeks followed by a one week rest period (1 cycle is 3 weeks).
• Patients will also receive corticosteroids, intravenous hydration and anti-emetic therapy prior to each treatment.
• A physical exam and bloodwork will be done each week of the treatment and every 2 cycles, reassessment of the tumor by the same imaging method to determine the baseline size will be conducted.
• Patients will remain on the study unless disease progression or intolerable toxicity occur.

• Esophageal Cancer
• Gastric Cancer
• GE Junction Cancer

• Drug: Taxotere
  Given once weekly for 2 weeks followed by a one week rest period (1 cycle is 3 weeks) Participants may continue on treatment unless there is disease progression or intolerable toxicities.
• Drug: Cisplatin
  Given once weekly for 2 weeks followed by a one week rest period (1 cycle is 3 weeks) Participants may continue on treatment unless there is disease progression or intolerable toxicities.
• Drug: Irinotecan
  Given once weekly for 2 weeks followed by a one week rest period (1 cycle is 3 weeks) Participants may continue on treatment unless there is disease progression or intolerable toxicities.

Inclusion Criteria:

• Histologically confirmed, incurable esophageal or gastric carcinoma (carcinoma = adenocarcinoma or squamous cell carcinoma)
• Measurable disease > 1cm (longest diameter) by spiral CT scan or > 2cm by other radiographic technique.
• Lesions must be measurable in at least one dimension.
• Bone lesions, ascites and effusions are not measurable.
• Irradiated lesions are not measurable yet lesions arising in previously irradiated fields are measurable.
• Age 18+ years.
• ECOG performance status 0 or 1.
• Life expectancy greater than 12 weeks.
• Adequate bone marrow function.
• Adequate renal function: creatinine equal to or less than 1.5 mg/dl.
• SGOT less than 2.5 x institutional upper limit of normal if alkaline phosphatase is within institutional upper limit of normal.
• Alkaline phosphatase less than 4.0 x upper limit of normal if SGOT is within institutional upper limit of normal.
• For patients with both SGOT and alkaline phosphatase elevations, SGOT must be less than 1.5 x institutional upper limit of normal and alkaline phosphatase must be less 2.5 x institutional upper limit of normal. For patients with liver metastases, however, SGOT may be < 3.0 x institutional upper limit of normal and alkaline phosphatase may be < 5.0 x institutional upper limit of normal as long as the total bilirubin is within the institutional upper limit of normal.

Exclusion Criteria:

• No prior chemotherapy (except as part of pre- or post-operative therapy, completed > 1 year prior to start date of this protocol).
• Patients who have received prior pelvic radiation therapy are ineligible. Other prior radiation therapy, however, is permitted, provided at least 4 weeks have elapsed since completion of this therapy and the initiation of this protocol.
• No myocardial infarction in the past six months.
• No major surgery in the past three weeks.
• No uncontrolled serious medical or psychiatric illness.
• No uncontrolled diarrhea.
• Patients with a peripheral neuropathy > grade 1 will be excluded.
• Women of childbearing potential must have a negative pregnancy test. Men and women of childbearing potential must use adequate contraception.
• No clinically apparent central nervous system metastases or carcinomatous meningitis.
• No other active malignancy other than non-melanoma skin cancer or in-situ cervical carcinoma. A resected cancer (other than in-situ carcinoma) must have demonstrated no evidence of recurrence for at least 3 years.
• Patients with history of severe hypersensitivity to irinotecan, cisplatin, taxotere or drugs formulated with polysorbate 80 must be excluded.

• Massachusetts General Hospital
• Beth Israel Deaconess Medical Center
• Brigham and Women's Hospital
• Aventis Pharmaceuticals