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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: IMMU-107 (hPAM4)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: multiple dose levels<br>1 of 3 different dose levels of 90Y-hPAM4 given once weekly for 3 weeks along with 4 weekly doses of gemcitabine. | Biological: IMMU-107 (hPAM4)<br>* 90Y-hPAM4 once weekly for 3 weeks gemcitabine once weekly for 4 weeks<br>* Other names: anti-mucin antibody;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety will be evaluated based upon physical examinations, hematology and chemistry laboratory testing as well as toxicity |  | over 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy and Clinical benefit measures such as quality of life, pain assessments, etc. |  | over 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, hPAM4, MUC1 antibody, cancer of the pancreas