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

Study Overview
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Brief Summary
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Safety study to determine highest dose of 90Y-hPAM4 can be safety administered

Detailed Description
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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.

Official Title
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A Phase I, Dose-Escalating Study to Investigate the Safety, Tolerability, Pharmacokinetics and Dosimetry of a Single Dose of 90YHumanized PAM4 IgG in Patients With Locally Advanced/Metastatic Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: 90Y-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, 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

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: Multi Dose levels<br>different doses of 90YhPAM4 will be given only once. | Biological: 90Y-hPAM4<br>* Single dose of 90Y-hPAM4 will be given and all patients will be followed for 12 weeks.<br>* Other names: MUC-1 antibody;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety MTD |  | over the first 12 weeks, then over 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| targeting, biodistribution, organ dosimetry |  | first 2 weeks | 
| pharmacokinetics (PK), antigenicity, |  | first 12 weeks | 
| efficacy |  | over first 12 weeks, then over 2 years | 

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