Dendritic Cell Vaccination and Docetaxel for Patients With Prostate Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Biological: mRNA transfected dendritic cell; Drug: Docetaxel

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Herlev, Denmark, 2730
    • Department of Oncology, Herlev Hospital
  • Herlev
    • Copenhagen, Herlev, Denmark, 2730
      • Center for Cancer Immune Therapy, Dept. of Haematology/Oncology

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:

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; DC vaccine (mRNA transfected dendritic cell) + Docetaxel	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).; Other Names: taxotere
Active Comparator: Arm B; Docetaxel alone	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).; Other Names: taxotere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunological response	The induction of vaccine specific immune responses will be assessed	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		4 years
Toxicity		2 years
Time to progression		4 years
Clinical response	Clinical response will be assessed using PSA measurements, pain response and PET/CT scans (according to RECIST)	2 years

Collaborators and Investigators

• Sponsor: Inge Marie Svane
• Investigators: Principal Investigator: Per Kongsted, MD, CCIT / Department of Oncology, Herlev Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: October 2, 2011
• First Submitted That Met QC Criteria: October 2, 2011
• First Posted (Estimate): October 5, 2011

Study Record Updates

• Last Update Posted (Estimate): August 16, 2016
• Last Update Submitted That Met QC Criteria: August 15, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: UR1121

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO