Phase II Study With Immunotherapy With Dendritic Cells and Tumor Infiltrating Lymphocytes in Solid Tumors

Melanoma Clinical Trial

Official title:

Phase II Study With Immunotherapy With Dendritic Cells and Tumor Infiltrating Lymphocytes in Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00610389
• Other study ID #: CD-2007-01
• Status: Recruiting
• Phase: Phase 2
• First received: January 28, 2008
• Last updated: May 7, 2010
• Start date: February 2008
• Est. completion date: December 2010

Study information

• Verified date: May 2010
• Source: Clinica Universidad de Navarra, Universidad de Navarra
• Contact: Ignacio Melero, MD, PhD
• Phone: +34 948255400
• Email: imelero[@]unav.es
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

Background: cellular immunotherapy with dendritic cells (DC) loaded with tumor antigens has shown clinical activity, although in a small number of patients. Therefore, is is mandatory to improve the results of this strategy and to closely monitor immunologic response and cell migration in order to improve our understanding of mechanisms of action and to settle future fields of development..

Objectives: Primary: to confirm clinical activity of this strategy, determining tumor response (RECIST criteria). Secondary: to determine: (1) safety; (2) antitumoral immune response and (3) DC migration in the organism

Methodology: phase II trial in patients with advanced renal cell carcinoma and melanoma. We will perform repeated immunizations with DC loaded with the patient´s tumor.

Description:

Background: cellular immunotherapy with dendritic cells (DC) loaded with tumor antigens has shown clinical activity, although in a small number of patients. Therefore, is is mandatory to improve the results of this strategy and to closely monitor immunologic response and cell migration in order to improve our understanding of mechanisms of action and to settle future fields of development..

Objectives: Primary: to confirm clinical activity of this strategy, determining tumor response (RECIST criteria). Secondary: to determine: (1) safety; (2) antitumoral immune response (through study of delayed hypersensitivity; ELISPOT; activity of Natural Killer cells; and serum cytokine concentrations); and (3) DC migration in the organism, by labeling with 111-Indium oxinate

Methodology: phase II trial in patients with advanced renal cell carcinoma and melanoma. We will perform repeated immunizations with mature DC loaded with autologous tumor. We will introduce the following novel elements to enhance efficacy (1) Pre-treatment with cyclophosphamide to reduce regulatory / suppressor T cells; (2) maturation/activation of DC induced by TNF-alfa, IFN-alfa and double stranded RNA (GMP-manufactured poly I:C), aimed at replication of the phenomena observed during a viral infection (3) intranodal DC administration in inguinal lymph nodes (4) four daily doses (repeated every 24 hours) in two cycles one month apart (5) scintigraphic follow-up of a tracing dose of 111-In labelled DC and (6) ) systemic treatment with PEG-IFN alfa and GM-CSF to potentiate activity.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 27
• Est. completion date: December 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of metastatic melanoma, renal cell carcinoma, or hepatocarcinoma (Child´s stage A or B) not amenable of curative treatment. For patients with hepatocarcinoma, treatment after embolization is allowed

• Measurable disease

• ECOG 0, 1 or 2.

• Adequate renal, hepatic and bone marrow function

• Availability of tumor tissue, for maturing dendritic cells

Exclusion Criteria:

• Clinically relevant diseases or infections.

• concurrent participation in other clinical trial or administration or other antitumoral treatment

• Concurrent cancer, with the exceptions allowed by the PI.

• Pregnant or breast feeding women

• immunosuppressant treatment

• known CNS metastasis

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Carcinoma, Renal Cell
• Melanoma
• Renal Cell Carcinoma

Intervention

Biological:
• immunotherapy with dendritic cells
We will administer four daily doses (repeated every 24 hours)o dendritic cells in two cycles one month apart. We will administer systemic treatment with PEG-IFN alfa and GM-CSF to potentiate activity.

Locations

Country	Name	City	State
Spain	Oncology Department. Clinica Universitaria de Navarra	Pamplona	Navarra

Sponsors (1)

Lead Sponsor	Collaborator
Clinica Universidad de Navarra, Universidad de Navarra

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate		2 months	No
Secondary	Immunological response		2 months	No