Dendritic Cell Vaccination and Docetaxel for Patients With Prostate Cancer

Phase 2

Completed

• Conditions: Prostatic Neoplasms
• Interventions: Biological: mRNA transfected dendritic cell; Drug: Docetaxel

• Registration Number: NCT01446731
• Lead Sponsor: Inge Marie Svane

Brief 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 evaluated 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.

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 Timeline

• Study Start: 2011-10
• Study First Submitted: 2011-10-02
• Study First Submitted QC: 2011-10-02
• Study First Posted: 2011-10-05
• Primary Completion: 2015-08
• Study Completion: 2015-08
• Results First Submitted: 2022-09-30
• Status Verified: 2024-01
• Results First Submitted QC: 2024-01-24
• Last Update Submitted: 2024-01-24
• Results First Posted: 2024-07-03
• Last Update Posted: 2024-07-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 43

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

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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, methotrexate)7. Co-treatment with other experimental treatments, other antineoplastic treatment.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	mRNA transfected dendritic cell	DC vaccine (mRNA transfected dendritic cell) + Docetaxel
Arm A	Docetaxel	DC vaccine (mRNA transfected dendritic cell) + Docetaxel
Arm B	Docetaxel	Docetaxel alone

Primary Outcome Measures

Name	Time	Method
Number of Patients With Immunological Response	2 years	The induction of vaccine specific immune responses will be assessed using interferon-gamma ELISPOT assay

Secondary Outcome Measures

Name	Time	Method
Number of Patients With PSA Response	2 years	PSA response will be evaluated by PSA measurements. A 50% decline in PSA is considered to be a response.
Number of Patients With Adverse Event Considered Related to the Dendritic Cell Vaccine	2 years	Graded according to common terminology criteria for adverse events (CTCAE) version 3.0.
Progression-free Survival	2 years	PFS was defined as the time from initiation of docetaxel to clinical, radiographic and/or PSA progression or death. PFS was described using the Kaplan-Meier method.

Trial Locations

Locations (2)

Department of Oncology, Herlev Hospital; 🇩🇰 Herlev, Denmark

Center for Cancer Immune Therapy, Dept. of Haematology/Oncology; 🇩🇰 Copenhagen, Herlev, Denmark