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

Primary Purpose

Cancer of the Prostate

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Dendritic cell application

About this trial

This is an interventional treatment trial for Cancer of the Prostate focused on measuring prostate cancer, dendritic cells, vaccination

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept 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%

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dendritic cell application

Arm Description

Outcomes

Primary Outcome Measures

tolerability and toxicity and feasibility of this regimen

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).

ex-vivo immunomodulation

Peripheral blood mononuclear cells (PBMC) isolation and in-vitro restimulation. Measurement of antigen specific immune responses.

Secondary Outcome Measures

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).

Overall survival

Full Information

NCT ID

NCT01897207

First Posted

June 26, 2013

Last Updated

August 14, 2015

Sponsor

Cantonal Hospital of St. Gallen

1. Study Identification

Unique Protocol Identification Number

NCT01897207

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2015

Overall Recruitment Status

Completed

Study Start Date

November 2002 (undefined)

Primary Completion Date

August 2009 (Actual)

Study Completion Date

October 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Cantonal Hospital of St. Gallen

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cancer of the Prostate

Keywords

prostate cancer, dendritic cells, vaccination

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dendritic cell application

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

Dendritic cell application

Intervention Description

S.C. injection of peptide pulsed autologous dendritic cells

Primary Outcome Measure Information:

Title

tolerability and toxicity and feasibility of this regimen

Time Frame

directly after vaccination (within 24 h)

Title

response rate or PSA response in non measurable disease

Description

Time Frame

Change from baseline in serum PSA at 6, 10 and 12 weeks

Title

ex-vivo immunomodulation

Description

Peripheral blood mononuclear cells (PBMC) isolation and in-vitro restimulation. Measurement of antigen specific immune responses.

Time Frame

before vaccination, after 6, 10, 12, and up to 85 weeks

Secondary Outcome Measure Information:

Title

pain relief

Description

Time Frame

Change from baseline in pain relief at 2, 4, 6, 8, 10 and 12 weeks

Title

Overall survival

Time Frame

From first date of treatment until dead

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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%

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thomas Cerny, Prof. Dr.

Organizational Affiliation

Department of Medical Oncology, Cantonal Hospital St. Gallen, Switzerland

Official's Role

Study Chair

12. IPD Sharing Statement

Learn more about this trial

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

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