Safety and Efficacy Study of 90Y-hPAM4 at Different Doses

radiolabeled anti-MUC1 humanized antibody) administered intravenously as a single dose to patients with locally advanced and/or metastatic pancreatic cancer. The primary objective is to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of 90Y-hPAM4 in this population. Secondary objectives include the assessment of tumor targeting, biodistribution, organ dosimetry and pharmacokinetics (PK) of 90Y-hPAM4 as determined by pre-therapy administration of 111In-hPAM4, the assessment of the antigenicity of 90Y-hPAM4, as determined by development of human anti-humanized antibodies (HAHA), and to obtain preliminary information on the efficacy of single dose 90Y-hPAM4 in this patient population.

Inclusion criteria

• Male or female patients, >18 years of age, who are able to understand and give written informed consent.
• Histologically or cytologically confirmed, Stage III or IV pancreatic adenocarcinoma.
• Patients with Stage III (locally advanced) disease must have documented progression after failing primary therapy
• Patients with Stage IV (metastatic) disease must not have received more than one chemotherapy regimen.
• Measurable disease by CT, with at least on lesion >1.5 cm in one dimension.
• Karnofsky performance status > 70 % (Appendix A).
• Expected survival > three months.
• At least 4 weeks beyond chemotherapy, radiotherapy, major surgery, other experimental treatments, and recovered from all acute toxicities.
• At least 2 weeks beyond corticosteroids, except low doses (i.e., 20 mg/day of prednisone or equivalent) to treat nausea or other illness such as rheumatoid arthritis
• Adequate hematology without ongoing transfusional support (hemoglobin > 10 g/dL, ANC > 1,500 per mm3, platelets > 150,000 per mm3)
• Adequate renal and hepatic function (creatinine and bilirubin ≤ 1.5 X IULN, AST and ALT ≤ 2.0 X IULN)
• Otherwise, all toxicity at study entry <Grade 1 by NCI CTC v3.0.

Exclusion criteria

• Women who are pregnant or lactating.
• Women of childbearing potential and fertile men unwilling to use effective contraception during study until conclusion of 12-week post-treatment evaluation period.
• Known metastatic disease to the central nervous system.
• Presence of bulky disease (defined as any single mass >10 cm in its greatest dimension)
• Patients with >Grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction.
• Prior treatment with nitrosureas, actinomycin-D, radioimmunotherapy or other antibody-based therapies (murine, chimeric, humanized or human) Prior radiation dose >3,000 cGy to the liver, >2,000 cGy to lungs and kidneys or prior external beam irradiation to a field that includes more than 30% of the red marrow.
• Patients with non-melanoma skin cancer or carcinoma in situ of the cervix are not excluded, but patients with other prior malignancies must have had at least a 5- year disease free interval.
• Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive.
• Known history of active coronary artery disease, unstable angina, myocardial infarction, or congestive heart failure present within 6 months or cardiac arrhythmia requiring anti-arrhythmia therapy.
• Known history of active COPD, or other moderate-to-severe respiratory illness present within 6 months.
• Known autoimmune disease or presence of autoimmune phenomena (except rheumatoid arthritis requiring only low dose maintenance corticosteroids).
• Infection requiring intravenous antibiotic use within 1 week.
• Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation