Dendritic Cell Vaccination and Docetaxel for Patients With Prostate Cancer

Prostatic Neoplasms Clinical Trial

Official title:

Dendritic Cell Vaccination in Combination With Docetaxel for Patients With Cancer Prostate - a Randomized Phase II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01446731
• Other study ID #: UR1121
• Status: Completed
• Phase: Phase 2
• First received: October 2, 2011
• Last updated: August 15, 2016
• Start date: October 2011
• Est. completion date: August 2015

Study information

• Verified date: August 2016
• Source: Herlev Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This is a randomized phase II trial including 40 patients with castration resistant metastatic cancer prostate (CRMPC).

Patients will be randomized between treatment with a dendritic cell vaccine plus docetaxel and docetaxel alone.

The primary objective is to evaluate the vaccine specific immune response and patients will be evlauated with blood tests and DTH reactions during the treatment course.

Secondary objectives are to evaluate clinical response by objective response (RECIST-criteria, 18F-NaF-PET/CT scan), PSA response, pain response and finally we determine time to progression and overall survival.

Description:

Treatment in details:

Dendritic cell (DC) vaccination The DC vaccine consists of adherent monocytes collected by leukapheresis. Monocytes are stimulated with GM-CSF and IL-4, and IL-1β, TNFα, IL-6 and PGE2 are used for further maturation.

DCs are transfected with PSA, PAP, survivin and hTERT mRNA. DC vaccines will only be given to patients in ARM A

Docetaxel:

Docetaxel will be given as an i.v. infusion every third week, 75 mg/m2 according to standard treatment. Patients will be pretreated with prednisolon before infusion with Docetaxel. Continuous treatment with prednisolon will not be administered.

Treatment schedule:

The DC vaccination will be administered once a week in two out of three weeks for the first 12 weeks. After 12 weeks the DC vaccination will be given once every three weeks as long as Docetaxel is given. If the disease does not progress but the patient stop treatment with Docetaxel (because of side effects) the vaccine treatment can continue until disease progression.

Evaluation in details:

Immunological evaluation:

Blood tests:

100 ml blood will be drawn from the patient together with the first (baseline), the third and the fourth infusion of Docetaxel, and every third month thereafter.

DTH:

DTH with 3 i.d. injections consisting of media (neg. test), naked DCs and mRNA transfected DCs will be performed at baseline (together with 1st vaccine), together with the 5th vaccine and after three months of treatment (8th vaccine). 48 hours after the DTH at 5th vaccine a biopsy will be taken from the DTH area.

Clinical evaluation:

PSA:

Patients will be evaluated with PSA measurements during the treatment. All patients will receive at least 4 treatments with Docetaxel even if PSA is rising.

18F-NaF ("bone") PET/CT scan: All patients will have a bone-PET/CT scan at baseline. For patients with measurable lesions a PET/CT scan will be performed every three months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histological verified CRMPC in progression, defined by

1. RECIST-criteria and/or

2. PSA increase to more than baseline in two consecutive measurements

2. Treatment with Docetaxel is indicated

3. Age > 18 years old

4. ECOG performance status =2

5. Life expectancy > 3 months

6. Normal organ function

Exclusion Criteria:

1. Other malignant tumors

2. Severe heard or lung disorders

3. Infection with HIV, hepatitis, tuberculosis.

4. Severe allergy or previous anaphylactic reactions

5. Active autoimmune disease

6. Treatment with immunosuppressive drugs (including prednisolon, methotrexat)7. Co-treatment with other experimental treatments, other antineoplastic treatment.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

Biological:
• mRNA transfected dendritic cell
Autologues monocytes are matured into dendritic cells which are then transfected with mRNA from PSA, PAP, survivin and hTERT. 5x 10e6 DCs are given as intradermal injections in the groin Day 8 and Day 15 in a 3 week period repeated 4 times and thereafter Day 8 in a 3 week period until progression (no maximum duration).

Drug:
• Docetaxel
Docetaxel 75 mg/m2 is given as an intravenous injection Day 1 every three weeks in a maximum of 12 cycles (1 cycle = 3 weeks).

Locations

Country	Name	City	State
Denmark	Center for Cancer Immune Therapy, Dept. of Haematology/Oncology	Copenhagen	Herlev
Denmark	Department of Oncology, Herlev Hospital	Herlev

Sponsors (1)

Lead Sponsor	Collaborator
Inge Marie Svane

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunological response	The induction of vaccine specific immune responses will be assessed	2 years	No
Secondary	Clinical response	Clinical response will be assessed using PSA measurements, pain response and PET/CT scans (according to RECIST)	2 years	No
Secondary	Toxicity		2 years	Yes
Secondary	Time to progression		4 years	No
Secondary	Overall survival		4 years	No