Clinical trial NCT00978913: Transfected Dendritic Cell Based Therapy for Patients With Breast Cancer or Malignant Melanoma
Official title: Evaluation of Dendritic Cells Transfected With Survivin, hTERT and p53 mRNA as a Treatment for Patients With Metastatic Breast Cancer or Malignant Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Malignant Melanoma
Keywords: dendritic cell
cancervaccine
breast cancer
malignant melanoma
Cyclophosphamide
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
First posted: 2009-09-17
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: Inclusion Criteria:

1. Histological verified metastatic breast cancer or malignant melanoma, in progression
2. ≥ 18 years
3. the patient must be habil
4. Performance status ≤ 1 on Zubrod-ECOG-WHO-scale
5. Leukocytes and platelets must be ≥normal. Hg ≥ 6.0
6. creatinin must be normal
7. Liverparametre \<2.5 x normal. Bilirubin \<30
8. Expected survival \> 3 months
9. Informed consent

11. At least one measurable lesion according to RECIST criteria.

Exclusion Criteria:

1. Indication for chemotherapy
2. Other malignancies
3. Brain metastases
4. severe medical condition
5. Acute/chronic infection with ex. HIV, hepatitis, tuberculose
6. Severe allergy
7. Autoimmune disease
8. Other treatment with immune suppressing agents, other anticancer agents or experimental drugs
9. Uncontrolled hypercalcemia.

Primary outcomes:
measure: to evaluate the toxicity of the vaccine in combination with Cyclophosphamide
timeFrame: biweekly
Secondary outcomes:
measure: to investigate the clinical tumor response and the duration
timeFrame: after 12 weeks
measure: to evaluate the duration of tumor and immunoresponse
timeFrame: 3, 6, 9 months
measure: to evaluate immune response
timeFrame: at 8 and 12 weeks
Other outcomes:
Locations:
city: Herlev
country: Denmark
facility: Department of Oncology, Herlev University Hospital
Study officials:
affiliation: Department of Oncology, Herlev University Hospital, Herlev Ringvej 75,2730 Herlev
name: Inge Marie Svane, prof.MD
role: STUDY_DIRECTOR
References: