Transfected Dendritic Cell Based Therapy for Patients With Breast Cancer or Malignant Melanoma

Study Overview
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Brief Summary
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The primary aim of this study is to evaluate the toxicity of the vaccine and the combination of the vaccine and Cyclophosphamide, and to evaluate the immune response induced by the vaccine. The secondary aim is to investigate the clinical tumour response and duration of tumour and immune response.

Detailed Description
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Phase I trial. Single center study; patients will be referred to the study center from other institutions in Denmark. 14 patients will be included in this phase I trial DC vaccination regime consists of primary 6 biweekly intradermal injections with transfected dendritic cells, followed by monthly injections until progression; Cyclophosphamide is used as vaccine adjuvant. Defined procedures are employed for generation of autologous dendritic cells for clinical application in a classified laboratory. Unmobilized leukapheresis will be used for isolation of large-scale mononuclear cells, and dendritic cells will be generated from monocytes by cytokine stimulation and transfected with mRNA encoding for hTERT, survivin and p53 if the tumour express p53. Frozen preparations of dendritic cells will be prepared using automated cryopreservation. Each patient will receive a minimum of 1x106 dendritic cells per treatment supplemented with Cyclophosphamide 50 mg twice a day every second week. Toxicity including autoimmunity will be evaluated using the Common Toxicity Criteria (CTC).

Official Title
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Evaluation of Dendritic Cells Transfected With Survivin, hTERT and p53 mRNA as a Treatment for Patients With Metastatic Breast Cancer or Malignant Melanoma

Conditions
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Breast Cancer, Malignant Melanoma

Intervention / Treatment
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* Biological: DC vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological verified metastatic breast cancer or malignant melanoma, in progression ≥ 18 years the patient must be habil Performance status ≤ 1 on Zubrod-ECOG-WHO-scale Leukocytes and platelets must be ≥normal. Hg ≥ 6.0 creatinin must be normal Liverparametre <2.5 x normal. Bilirubin <30 Expected survival > 3 months Informed consent 11. At least one measurable lesion according to RECIST criteria. Exclusion Criteria: Indication for chemotherapy Other malignancies Brain metastases severe medical condition Acute/chronic infection with ex. HIV, hepatitis, tuberculose Severe allergy Autoimmune disease Other treatment with immune suppressing agents, other anticancer agents or experimental drugs Uncontrolled hypercalcemia.

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: DC vaccination and Cyclophosphamide<br> | Biological: DC vaccine<br>* DC vaccination, one vaccine biweekly<br>* Other names: Cyclophosphamide, Sendoxan®, Baxter;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to evaluate the toxicity of the vaccine in combination with Cyclophosphamide |  | biweekly | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to investigate the clinical tumor response and the duration |  | after 12 weeks | 
| to evaluate the duration of tumor and immunoresponse |  | 3, 6, 9 months | 
| to evaluate immune response |  | at 8 and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dendritic cell, cancervaccine, breast cancer, malignant melanoma, Cyclophosphamide