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

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.

Study Overview

• Status: Completed
• Conditions: Cancer of the Prostate
• Intervention / Treatment: Biological: Dendritic cell application

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dendritic cell application	Biological: Dendritic cell application; S.C. injection of peptide pulsed autologous dendritic cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tolerability and toxicity and feasibility of this regimen		directly after vaccination (within 24 h)
response rate or PSA response in non measurable disease	The given time frame reflects the minimum of PSA values. From Patients receiving more than 6 DC vaccination every 4 weeks PSA was determined until the end of DC vaccination (longest was one and a half year).	Change from baseline in serum PSA at 6, 10 and 12 weeks
ex-vivo immunomodulation	Peripheral blood mononuclear cells (PBMC) isolation and in-vitro restimulation. Measurement of antigen specific immune responses.	before vaccination, after 6, 10, 12, and up to 85 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pain relief	Changes in pain intensity will be assessed by summarizing score items 9 and 19 of the European Organisation for Research and Treatment of Cancer (EORTC)quality of life questionnaire (QLQ-C30) quality. Additionally, analgesic consumption will be rated by a pain treatment score (PTS).	Change from baseline in pain relief at 2, 4, 6, 8, 10 and 12 weeks
Overall survival		From first date of treatment until dead

Collaborators and Investigators

• Sponsor: Cantonal Hospital of St. Gallen
• Investigators: Study Chair: Thomas Cerny, Prof. Dr., Department of Medical Oncology, Cantonal Hospital St. Gallen, Switzerland

Study record dates

Study Major Dates

• Study Start: November 1, 2002
• Primary Completion (ACTUAL): August 1, 2009
• Study Completion (ACTUAL): October 1, 2011

Study Registration Dates

• First Submitted: June 26, 2013
• First Submitted That Met QC Criteria: July 9, 2013
• First Posted (ESTIMATE): July 11, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): August 17, 2015
• Last Update Submitted That Met QC Criteria: August 14, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: prostate cancer; vaccination; dendritic cells
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: SG226_02