Phase I/II Study of Vaccination With Antigen Loaded Dendritic Cells (DCs) in Hormone-Refractory Prostate Cancer

Cantonal Hospital of St. Gallen

Status and phase

Completed

Phase 2

Phase 1

Conditions

Cancer of the Prostate

Treatments

Biological: Dendritic cell application

Study type

Interventional

Funder types

Other

Identifiers

NCT01897207

SG226_02

Details and patient eligibility

About

The main aim of this trial is to assess the response rate, the feasibility and toxicity of the treatment with antigen loaded Dendritic Cell Vaccination in Prostate Cancer patients. Furthermore we want to investigate biological responses by measuring markers of in-vivo and ex-vivo immunomodulation.

Full description

Dendritic cell (DC)-based immunotherapy is a promising approach to augment tumor antigen-specific T cell responses in cancer patients. However, tumor escape with down-regulation or complete loss of target antigens may limit the susceptibility of tumor cells to the immune attack. Concomitant generation of T cell responses against several immunodominant antigens may circumvent this potential drawback. In this phase I/II clinical trial, the investigators determined the immunostimulatory capacity of autologous DC pulsed with multiple T cell epitopes derived from four different prostate-specific antigens in patients with advanced hormone-refractory prostate cancer. Autologous DC of HLA-A*0201-positive patients are loaded with antigenic peptides derived from prostate stem cell antigen, prostatic acid phosphatase, prostate-specific membrane antigen, and prostate-specific antigen. A strict quality control concerning the expression of surface markers and the migratory capacity of the DC secured optimal stimulatory capacity. DC were applied intradermally six times at biweekly intervals followed by monthly booster injections. Tolerability and PSA response will be investigated. Antigen-specific immune responses will be quantified.

Enrollment

15 patients

Sex

Male

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

histologically or cytologically proven prostatic carcinoma
proven hormonal resistance: tumor progression after orchiectomy or during treatment with hormonal agents. Patients treated with antiandrogens, such as flutamide (Flucinom) or bicalutamide (Casodex), should have been discontinued the drug 6 weeks prior to the trial entry followed by no tumor response within this 6 weeks
not amenable to curative therapy
patients with measurable and non-measurable disease may be included. Bone lesions only are considered to be non-measurable
two consecutive increases of prostate-specific antigen (PSA) should be documented over a previous reference value (N°1). The first increase in PSA (N°2) should occur a minimum of one week from the reference value and be confirmed (N°3). If this value is less than the previous value, the patient is still eligible if the next PSA(N°4) is found to be higher than the second PSA. Serum levels of prostate-specific antigen must be at least 10 microg/l
Previous radiotherapy is allowed if it has been stopped 4 weeks or more before the trial treatment and did not involve lesions used to evaluate activity of the trial drugs
one previous chemotherapy (including Estracyt) is allowed, but the chemotherapy should have been stopped at least 6 weeks before study entry
age >18 years
performance status 0,1,2 (ECOG, Appendix I)
no concurrent therapy with steroids
no uncontrolled infections
live expectancy more than 3 months
Human leukocyte antigen (HLA)-Type has to be HLA*A201
neutrophile count >1500/microl and thrombocytes >100 000/microl
creatinine <1.5 of upper normal level
adequate liver function with bilirubin <2 of upper normal level, alanine aminotransferase (ALAT) and aspartate transamionase (ASAT) < 3 x upper normal level
absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
before patient registration/randomization, informed consent must be given according to good clinical practice (GCP), and national/local regulations

Exclusion criteria

serious concomitant disease (cardiac, pulmonary and others)
brain metastasis
previous splenectomy or radiotherapy to the spleen
concurrent therapy with immunosuppressive drugs
chronic immunosuppression (includes transplantation or HIV-infection) HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) (test required) or any other severe uncontrolled infection other neoplastic diseases except: curatively treated basal cell or squamous cell carcinoma of the skin or relapse free for more than 5 years after curative treatment of a neoplasm
treatment with other investigational drugs during the last month
severe autoimmune disease
chemotherapy, radiotherapy or immunotherapy less than 6 weeks before study entry
Ejection fraction (measured by echocardiography) < 40%