A Pilot Study Assessing Intra-Metastasis Administration of Autologous KLH-pulsed Dendritic Cells With Tumoral Radiation Therapy in Patients With Metastatic Pancreatic Carcinoma

Study Overview
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Brief Summary
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This study is being done to determine whether it is possible to use an investigational vaccine that consists of dendritic cells in patients with pancreas cancer. Dendritic cells are immune cells that are obtained from your blood that are important in the body's immune response to foreign substances. The vaccine would be injected directly into a tumor that has spread to the liver after a short course of radiation therapy has been given to that tumor. The study will try to determine if this treatment would be safe and effective in treating this cancer. This is a phase 1 pilot study of this treatment. Phase 1 trials test the best way to give a treatment where little is known about its possible risks or benefits. Phase 2 studies then test the possible benefits of a treatment and may show the specific situations where they are seen. Promising treatments are then tested in Phase 3 trials which compare the new treatment to standard treatment in a larger group of patients. Phase 4 trials are those conducted on a treatment after it has been approved for general use outside of research. A pilot study tests a treatment in a small number of patients to learn if and how the treatment could be tested in a larger group. Pilot studies can be performed at any phase but are commonly performed in the earliest phases of research on a treatment.

Conditions
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Metastatic Pancreatic Carcinoma

Intervention / Treatment
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* Radiation: tumoral irradiation
* Biological: Dendritic cell vaccination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologic diagnosis of pancreatic carcinoma Radiologic evidence of hepatic metastasis with at least one lesion > 2.0 cm that is amenable to ultrasound or CT guided intra-tumoral DC injection Age > 18 Life expectancy > 3 months Karnofsky Performance Status > 70% Patients must not have received any anti-neoplastic chemotherapy, immunotherapy or radiotherapy for the four weeks preceding entry onto the study (six weeks for nitrosoureas and mitomycin C). Adequate baseline hematopoietic function defined as WBC (white blood cell) > 3000/mm3, hemoglobin > 9g/dl, and platelet count > 100,000/mm3. Adequate baseline organ function defined as creatinine < 2.0, total bilirubin < 2.0 mg/dl Patients taking warfarin are not eligible. Adequate coagulation function defined as PT (prothrombin time) < 15, INR < 1.5 and PTT (partial thromboplastin time) < 35. Ability to give informed consent Exclusion Criteria: Previous anti-tumor vaccine therapy Prior hepatic irradiation Known brain metastases History of prior autoimmune diseases (e.g. SLE (systemic lupus erythematosus), rheumatoid arthritis, myasthenia gravis) Regular corticosteroid use within the past one year or any corticosteroid use in the four weeks preceding study entry Evidence of HIV infection, AIDS, Hepatitis B or Hepatitis C infection Active bacterial, fungal or viral infection Pregnancy or lactation; women of childbearing potential and men must agree to use effective contraception during the course of this clinical trial Uncontrolled or unstable medical conditions including angina, arrhythmias, bleeding, or thromboembolic conditions, Any medical or psychiatric illness that might compromise the patients ability to tolerate treatment

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Participants will receive tumoral irradiation and dendritic cell vaccination. | Radiation: tumoral irradiation<br>* On day 1 of the study treatment, patients will begin tumoral irradiation, which will be given daily for 4 days in 6Gy fractions (days 1 through 4)<br>Biological: Dendritic cell vaccination<br>* Three intra-tumoral injections of 1 ml cell suspensions of KLH (keyhole limpet hemocyanin)- pulsed DC (dendritic cells) will be delivered percutaneously under ultrasound into a selected hepatic metastasis in the outpatient setting.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants That Patients Complete Radiation Therapy, All Three Vaccinations, and Evaluation for Tumor Response Four Weeks After the Third Vaccination. | The primary objective of this study was to evaluate the safety and feasibility of this combined modality protocol in patients with metastatic pancreatic carcinoma. The treatment will be deemed feasible if 80% or more patients complete radiation therapy, all three vaccinations, and evaluation for tumor response four weeks after the third vaccination. | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients That Respond to Treatment | To evaluate the anti-tumor response as determined by RECIST criteria | 10 weeks |