Study Chairman:  Robert A. Wolff, MD
Study Sponsor:  Brown University Oncology Group

TREATMENT SCHEDULE:

Gemcitabine: One dose over 30 minutes every week for 7 weeks, with a one-week break. Patients with stable or responding disease based on the week-8 CT scan will continue on treatment. Thereafter, gemcitabine will be given one doseevery week for 3 weeks, with a one-week break.

Herceptin: One dose over 90 mins, week 1, then one dose per week IV over 30-90 minutes for 7 weeks. Patients with stable or responding disease based on the week 8 CT scan will continue on weekly Herceptin treatments.

STUDY RATIONALE: (excerpted from the protocol abstract)

The HER-2/neu oncogene is overexpressed in approximately 40% of pancreatic adenocarcinomas. Her-2/neu overexpression may transform cells by constitutive activation of signal transduction pathways. Furthermore, by stimulating cell proliferation, HER-2/neu overexpression may promote tumor cell growth and metastasis. Gene amplification and increased gene transcription have been implicated in HER-2/neu overexpression in pancreatic cancer.

Antibodies directed at p185 (the HER-2/neu protein) can inhibit the growth of tumors and of trnasformed cells that express high levels of this receptor. Clinical trials have shown that the human anti-p185HER2 monoclonal antibody, Herceptin, has substantial activity in metastatic adenocarcinomas of the breast that overexpress HER-2/neu. We therefore propose to evaluate the addition of Herceptin to gemcitabine in metastatic pancreatic carcinomas that overexpress HER-2/neu.

Slamon et al performed a randomized phase III trial to evaluate the addition of Herceptin to first-line chemotherapy for metastatic breast cancer. Response rate to paclitaxel and Herceptin was 57% as compared to 25% from paclitaxel alone. Cardiac toxicity was also increased in patients who received paclitaxel and Herceptin (4%) as compared to paclitaxel alone (0%).

ELIGIBILITY CRITERIA

Inclusion

Patients are required to have biopsy-confirmed metastatic pancreatic cancer that overexpresses HER-2/neu determined by DAKO immunohistochemical staining. This may require a core biopsy at M. D. Anderson.

Patients must have cancer that is measurable on a CT or MRI. Ascites is not measurable.

Must be more than 2 weeks since previous chemotherapy or radiation.

Must be more than 18 years of age with adequate blood counts and liver function tests.

Must be capable of giving informed consent.

Exclusion

Patients whose biopsies show that the tumor does NOT overexpress the HER2/neu gene will not continue on the protocol.

Patients with unstable angina, or history of heart attack or congestive heart failure are not eligible.

Pregnant or lactating women are not eligible.

Patients who have received prior treatment with gemcitabine, herceptin, or any type of anthracycline are not eligible.