A Study of Fractionated 90Y-hPAM4 Plus Gemcitabine in Pancreatic Cancer Patients Receiving at Least 2 Prior Therapies.

Study Overview
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Brief Summary
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90Y-hPAM4 is administered weekly for 3 weeks combined with 4 weekly doses of gemcitabine to assess. This is a dose escalation study of 90Y-hPAM4 to assess which dose is safe and effective as 3rd line treatment for patients with metastatic pancreatic cancer. Patients are then followed weekly for 12 weeks and afterwards for up to 1 year.

Official Title
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A Ph Ib Study of Fractionated 90Y-hPAM4 Plus Gemcitabine in Pancreatic Cancer Patients Receiving at Least 2 Prior Therapies.

Conditions
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Metastatic Pancreatic Adenocarcinoma, Pancreatic Cancer, Metastatic Pancreatic Cancer

Intervention / Treatment
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* Drug: 90Y-hPAM4
* Drug: 90Y-hPAM4
* Drug: 90Y-hPAM4 + gemcitabine


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 IV (metastatic) disease, including patients who underwent surgery but had incomplete resections Previously treated and received two prior treatment regimens for advanced disease Karnofsky performance status ≥ 60 % (Appendix A) Expected survival ≥ 3 months At least 4 weeks beyond major surgery, 2 weeks beyond chemotherapy, radiotherapy, other experimental treatments 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 > 9 g/dL, ANC > 1,500 per mm3, platelets > 100,000 per mm3) Adequate renal and hepatic function (creatinine and bilirubin ≤ 1.5 X IULN, AST and ALT ≤ 2.0 X IULN [5.0 X IULN if due to liver metastases]) Otherwise, all toxicity at study entry ≤ Grade 1 by NCI CTC v3.0 or recovered to baseline or discussed with and agreed to with Immunomedics' Medical Monitor. 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 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 3-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 (other than stable atrial fibrillation) 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 90Y-hPAM4<br>90Y-hPAM4 is administered weekly for 3 weeks | Drug: 90Y-hPAM4<br>* 90Y-hPAM4 will be administered weekly for 3 weeks in conjunction with gemcitabine which will be administered weekly x 4.<br>* Other names: Clivatuzumab Tetraxetan;Drug: 90Y-hPAM4<br> <br> * Other names: clivatuzumab tetraxetan;|
| Experimental: 90Y-hPAM4 + gemcitabine<br>90Y-hPAM4 is administered weekly for 3 weeks, while gemcitabine is administered weekly for 4 weeks. | Drug: 90Y-hPAM4<br>* 90Y-hPAM4 will be administered weekly for 3 weeks in conjunction with gemcitabine which will be administered weekly x 4.<br>* Other names: Clivatuzumab Tetraxetan;Drug: 90Y-hPAM4<br> <br> * Other names: clivatuzumab tetraxetan;Drug: 90Y-hPAM4 + gemcitabine<br> <br> * Other names: clivatuzumab tetraxetan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (change in hematology and chemistry laboratory values from baseline) | Acute safety will be assessed weekly for the 1st 12 weeks, and then for up to 1 year after completion of study drug treatment. Safety will be assessed by comparing baseline hematology and chemistry laboratory values with the values obtained weekly after treatment. Safety will also be assessed by the adverse events that are reported. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dosage determination | This study is also being done to determine an acceptable 90Y-hPAM4 dose in this patient population. It is anticipated that enrollment will occur over 2 years. | 2 years | 
| Efficacy | Efficacy will be assessed for at least 1 year after treatment with study drug. CT scans will be used to determine treatment response. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic pancreatic adenocarcinoma, pancreatic cancer, metastatic pancreatic cancer