Safety and Efficacy Study of 90Y-hPAM4 at Different Doses
- Conditions
- Pancreatic Cancer
- Interventions
- Biological: 90Y-hPAM4
- Registration Number
- NCT00597129
- Lead Sponsor
- Gilead Sciences
- Brief Summary
Safety study to determine highest dose of 90Y-hPAM4 can be safety administered
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 21
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Multi Dose levels 90Y-hPAM4 different doses of 90YhPAM4 will be given only once.
- Primary Outcome Measures
Name Time Method safety MTD over the first 12 weeks, then over 2 years
- Secondary Outcome Measures
Name Time Method efficacy over first 12 weeks, then over 2 years targeting, biodistribution, organ dosimetry first 2 weeks pharmacokinetics (PK), antigenicity, first 12 weeks
Trial Locations
- Locations (4)
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Goshen Cancer Center
🇺🇸Goshen, Indiana, United States
University of Medicine and Dentistry
🇺🇸Newark, New Jersey, United States
Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States