Prostatic Neoplasms
Conditions
Keywords
Prostate cancer
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.
Interventions
BIOLOGICALmRNA transfected dendritic cell
Autologous 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).
DRUGDocetaxel
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).
Sponsors
Inge Marie Svane
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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, methotrexate)7. Co-treatment with other experimental treatments, other antineoplastic treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Immunological Response | 2 years | The induction of vaccine specific immune responses will be assessed using interferon-gamma ELISPOT assay |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A DC vaccine (mRNA transfected dendritic cell) + Docetaxel
mRNA transfected dendritic cell: Autologous 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).
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). | 21 |
| Arm B Docetaxel alone
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). | 19 |
| Total | 40 |
Baseline characteristics
| Characteristic | Arm B | Total | Arm A |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 38 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 1 Participants |
| Age, Continuous | 70 years | 71 years | 71 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 40 Participants | 21 Participants |
| Region of Enrollment Denmark | 19 participants | 40 participants | 21 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 19 Participants | 40 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 21 | 19 / 19 |
| serious Total, serious adverse events | 3 / 21 | 1 / 19 |
Outcome results
Primary
Number of Patients With Immunological Response
The induction of vaccine specific immune responses will be assessed using interferon-gamma ELISPOT assay
Time frame: 2 years
Population: Biological material for testing was available for 18 patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A | Number of Patients With Immunological Response | 9 Participants |
Secondary
Number of Patients With Adverse Event Considered Related to the Dendritic Cell Vaccine
Graded according to common terminology criteria for adverse events (CTCAE) version 3.0.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A | Number of Patients With Adverse Event Considered Related to the Dendritic Cell Vaccine | 2 Participants |
Secondary
Number of Patients With PSA Response
PSA response will be evaluated by PSA measurements. A 50% decline in PSA is considered to be a response.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A | Number of Patients With PSA Response | 11 Participants |
| Arm B | Number of Patients With PSA Response | 8 Participants |
Secondary
Progression-free Survival
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.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Progression-free Survival | 5.7 months |
| Arm B | Progression-free Survival | 5.5 months |