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

NCT ID: NCT00610389

Last Updated: 2010-05-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2010-12-31

Brief 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.

Detailed 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.

Conditions

Renal Cell Carcinoma; Melanoma; Carcinoma, Hepatocellular

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

immunotherapy with dendritic cells

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinica Universidad de Navarra, Universidad de Navarra

OTHER

Sponsor Role: lead

Responsible Party

Universidad de Navarra

Principal Investigators

Ignacio Melero, MdPhD

Role: PRINCIPAL_INVESTIGATOR

University of Navarra

Locations

Oncology Department. Clinica Universitaria de Navarra

Pamplona, Navarre, Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Ignacio Melero, MD, PhD

Role: CONTACT

imelero@unav.es

+34 948255400

Other Identifiers

CD-2007-01

Identifier Type: -

Identifier Source: org_study_id