Safety and Efficacy Study of Different Doses of 90Y-hPAM4 Combined With Gemcitabine in Pancreatic Cancer

A Phase Ib/II Study of Fractionated 90Y-hPAM4 Plus Gemcitabine in Patients With Previously Untreated Advanced Pancreatic Cancer.

This is a study to test whether different doses of 90Y-hPAM4 are safe to give in combination with gemcitabine in patients with previously untreated pancreatic cancer.

Patients receive a 4-week treatment cycle with once-weekly 30-minute gemcitabine infusions beginning one week prior to the first 90Y-hPAM4dose and continuing during the 3 consecutive weeks over which once weekly 90Y-hPAM4 doses are given. Depending on toxicity, patient cohorts will receive one of several possible 90Y and gemcitabine dose combinations. Post-treatment evaluations conducted until instituting another 90YhPAM4 treatment cycle, maintenance gemcitabine or for a maximum period of 12 weeks.

Inclusion Criteria:

• Male or female patients, >18 years of age, who are able to understand and give written informed consent.
• Histologically or cytologically confirmed pancreatic adenocarcinoma.
• Stage III (locally advanced, unresectable) or Stage IV (metastatic) disease, including patients who underwent surgery but had incomplete resections.
• Treatment naïve (no prior chemotherapy, radiotherapy or investigational agents for pancreatic cancer)
• Karnofsky performance status > 70 % (Appendix A).
• Expected survival > 3 months.
• At least 4 weeks beyond major surgery 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 > 11 g/dL, ANC > 2,000 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 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 or prevent completion of study procedures and follow-up examinations.