safety and efficacy study of 90y-hpam4 at different doses

Conditions: Pancreatic Cancer

Summary: safety study to determine highest dose of 90y-hpam4 can be safety administered

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.

Eligibility criteria:
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

Keywords: pancreatic cancer cancer of the pancreas pancreas cancer