Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Dacarbazine

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Sorafenib: 2x400 mg daily PO (2 tablets (200 mg each) each AM and PM). DAY 1-56.

DTIC: 1-hour IV infusion 1000mg/m2 DAY 14 and 42.

Sorafenib (Nexavar), Dacarbazine (DTIC)

Reinhard Dummer, MD

Investigation of the metabolic activity of sorafenib and sorafenib plus dacarbazine on melanoma metastasis in patients with melanoma stage III or IV on the basis of PET/CT, LDH and S-100 evaluation. As we hypothezise a direct influence on the transcriptome by these drugs via antiproliferative or apoptotic signals, biopsies of melanoma skin metastases will be assessed with microarrays and direct changes will be revealed. If positive effects on the transcriptional profiles of metastases are revealed, patients with metastatic melanomas would benefit from these drugs resulting in tumor regressions.

Therefore, a total of 12 patients with skin- or superficial lymph node metastases with a diameter of at least 1 cm will be chosen for sorafenib therapy over 56 days per os twice daily with each 400 mg and, additionally, on day 14 and 42, intravenous dacarbazine infusion (volume depending on the body surface area (1000 mg/m2)). Before treatment with sorafenib, before treatment with dacarbazine, and after treatment, S100 and LDH will be measured in serum, PET/CT will be conducted and biopsy will be taken out of one skin metastasis on the same day.

A total of 12 patients with skin- or superficial lymph node metastases with a diameter of at least 1 cm will be chosen for sorafenib therapy over 56 days per os twice daily with each 400 mg and, additionally, on day 14 and 42, intravenous dacarbazine infusion (volume depending on the body surface area (1000 mg/m2)).

On screening day, the medical history as well as the physical examination with determining the vital signs and the analyzing the coagulation status in the venous blood are conducted. In women, a pregnancy test will be conducted. On screening day, as well as on day 10, 16, 35 and 60, venous blood is taken for examination of hematology (hemoglobin, hematocrit, red blood cell (RBC) count, platelets, white blood cell (WBC) count with differential (total neutrophils, lymphocytes, monocytes, eosinophils and basophils), biochemistry (sodium, potassium, urea, creatinine, phosphate, glucose, alanine aminotransferase (ALT), gGT, alkaline phosphatase, total bilirubin, albumin, total lipid status with LDL-cholesterol, HDL-cholesterol, triglyceride), S-100, LDH, and for asservation of 40 ml EDTA and 10 ml Serum. At every consultation (screening day, day 1, 10, 14, 16, 35, 42, 60), concomitant medication will be recorded, and vital signs will be determined. At every consultation except of screening day and day 1, adverse events will be reported. FDG-PET/CT is conducted on screening day, day 10, 16 and 60; afterward, one cutaneous metastasis which was included in previous PET/CT scan, is biopsied for investigating its gene processing profile (day 60 is optional).

Monocentric Pilot Study Investigating the Metabolic Activity of Melanoma in Vivo During Sorafenib and Dacarbazine

University of Zurich

Reinhard Dummer/Prof. Dr. med.

Vaccines

Immunomodulating Agents

HLA-A2.1 patients are vaccinated with dendritic cells loaded with MHC Class I restricted epitopes of tumor antigens gp100 and tyrosinase

HLA-A2.1 and HLA-DR4 patients are vaccinated with dendritic cells loaded with MHC Class I and II restricted epitopes of tumor antigens gp100 and tyrosinase

HLA-A2.1 and/or HLA-DR4 patients are vaccinated with dendritic cells transfected with mRNA encoding tumor antigens gp100 and tyrosinase

autologous dendritic cell vaccine

Prof. C.J.A. Punt, MD, PhD

Prof. G.J. Adema, PhD

Dendritic cells (DCs)are the most potent antigen-presenting cells of the immune system, as such they are able to direct the immune system specifically against cancer cells. Currently DCs are used in clinical vaccination studies and immunological and clinical responses have been observed. For inducing anti-tumor immunity, the DCs have to be loaded with tumor antigen (i.e. molecular structures that are presented by the tumor, that are recognized by the immune system). Currently most studies use tumor peptides (small protein fragments) for this purpose. This approach has several disadvantages: only patients with a certain HLA-type can be treated and the immune response that is induced by the vaccine is limited to the used peptides. These disadvantages do not exist when the DCs present antigen which is endogenously processed, for example after RNA transfection. For this reason we investigate the immunogenicity of DCs that are pulsed with peptides or transfected with mRNA encoding melanoma associated antigens in stage III and IV melanoma patients.

Peptide-pulsed vs. RNA-transfected Dendritic Cell Vaccines in Melanoma Patients

In Vivo Responses of DC Vaccines Presenting HLA Class I and II Restricted Tumor Epitopes Either by Peptide-pulsing or mRNA Transfection in Melanoma Patients

Dutch Cancer Society

Radboud University Medical Center

Peptide-pulsed dendritic cells

Prof. C.G. Figdor, PhD

Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. As such they are currently used in clinical vaccination protocols in cancer patients, and both immunological and clinical responses have been observed. For these therapies accurate delivery to target organs is essential. Correct delivery and subsequent migration of vaccinated DCs to regional lymph nodes is of paramount importance for effective stimulation of the immune system. Currently it is not known what the best route of administration is for DC vaccines.

Using magnetically labeled DCs, we investigate the potential of MRI cell tracking to monitor DC therapy. This is investigated in stage III/IV melanoma patients in whom a regional lymph node dissection is scheduled. Autologous monocyte-derived DCs are labeled with the clinically approved superparamagnetic iron oxide (SPIO) formulation Endorem and 111In-oxine and injected either in the skin or directly in lymph nodes under ultrasound guidance. Two days after vaccination patients are monitored with scintigraphy and MR imaging. Lymph nodes are then resected. Subsequently patients receive 3 more vaccination with DCs. During and after therapy immune responses against the used melanoma peptides are monitored.

Dendritic Cell Vaccination in Melanoma Patients Scheduled for Regional Lymph Node Dissection

Active Immunization of Patients With Stage III and IV Melanoma in Whom a Regional Lymph Node Dissection is Planned, With Peptide-Pulsed Dendritic Cells: Evaluation of in Vivo Immune and Clinical Response and Migration

C.J.A. Punt, MD, PhD

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Monocentric Pilot Study Investigating the Metabolic Activity of Melanoma in Vivo During Sorafenib and Dacarbazine	NCT00794235	Melanoma Stage ... No Prior Chemot...	Sorafenib (Nexa...	18 Years -	University of Zurich
Peptide-pulsed vs. RNA-transfected Dendritic Cell Vaccines in Melanoma Patients	NCT00243529	Melanoma Stage ...	autologous dend...	18 Years - 75 Years	Radboud University Medical Center
Monocentric Pilot Study Investigating the Metabolic Activity of Melanoma in Vivo During Sorafenib and Dacarbazine	NCT00794235	Melanoma Stage ... No Prior Chemot...	Sorafenib (Nexa...	18 Years -	University of Zurich
Dendritic Cell Vaccination in Melanoma Patients Scheduled for Regional Lymph Node Dissection	NCT00243594	Melanoma Stage ...	Peptide-pulsed ...	18 Years - 75 Years	Radboud University Medical Center
Peptide-pulsed vs. RNA-transfected Dendritic Cell Vaccines in Melanoma Patients	NCT00243529	Melanoma Stage ...	autologous dend...	18 Years - 75 Years	Radboud University Medical Center
Peptide-pulsed vs. RNA-transfected Dendritic Cell Vaccines in Melanoma Patients	NCT00243529	Melanoma Stage ...	autologous dend...	18 Years - 75 Years	Radboud University Medical Center

Spots Global Cancer Trial Database for melanoma stage iii or iv