Vaccine Therapy in Treating Patients With Non-Metastatic Prostate Cancer
RATIONALE: Vaccines made from tumor cells or dendritic cells may help the body build an effective immune response to kill tumor cells. It is not yet known which vaccine is more effective in treating patients with prostate cancer.
PURPOSE: This phase II trial is studying how well the combination of a proven effective allogenic whole prostate carcinoma cell (APCC) vaccine co-administered with ex vivo generated dendritic cells (DCs)(DC-APCC) extend the time to prostate cancer progression.
Biological: allogeneic tumor cell vaccine
Biological: therapeutic autologous dendritic cells
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial to Determine the Safety, Tolerability and Efficacy of an Allogeneic Whole Cell Vaccine Administered With Autologous Myeloid Dendritic Cells to Patients With Non-Metastatic Androgen Independent Prostate Carcinoma|
- Number of Participants Who Are Progression Free at One Year [ Time Frame: One year ] [ Designated as safety issue: No ]Progression free was defined as being free of radiographically detectable disease/metastases at one year after registration and having a prostate-specific antigen (PSA) level <200.0 ng/mL.
- Number of Participants With Severe Adverse Events [ Time Frame: Every cycle during treatment (up to 14 cycles) ] [ Designated as safety issue: Yes ]Severe adverse events were defined as grade 3 or higher, regardless of attribution to study drugs. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.
- Time to Prostate-cancer Specific Mortality [ Time Frame: Registration to Prostate-cancer specific mortality (Up to 3 years) ] [ Designated as safety issue: No ]
- Time to Prostate-specific Antigen (PSA) Progression [ Time Frame: Registration to PSA progression (Up to 3 years) ] [ Designated as safety issue: No ]
In patients whose PSA has not decreased, progressive disease is a 25% increase over the baseline (on-study) and an increase in the absolute-value PSA level by at least 5 ng/mL, which is confirmed by a second value. In patients whose PSA has decreased but has not reached response criteria, progressive disease would be considered to have occurred when PSA increases 25% over the nadir, provided that the increase is a minimum of 5 ng/mL and is confirmed.
The start of the time to PSA progression is the day treatment is initiated. If at least a 50% decline in PSA has been achieved, the end date is the time the PSA has increased 50% above the nadir at a minimum of 5 ng/mL (this is the same as the parameter for PSA response). For patients without a PSA decrease of this magnitude (or no decrease in PSA), the end point for progression will be calculated at the time a 25% increase in PSA has been achieved (see above). All end dates require a confirmatory PSA.
- Duration of PSA-based Response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
PSA-based response was defined as a PSA decline of at least 50%, which must be confirmed by a second PSA value in 4 or more weeks later.
The duration of PSA-based response are measured from the first time point at which the PSA has declined by at least 50% (which must eventually be confirmed by a second value) until PSA has increased back to 50% of the original on-study value.
- Change From Baseline in Quality of Life (QOL) as Measured by the EORTC QLQ-C30 Questionnaire [ Time Frame: Baseline and cycle 1 ] [ Designated as safety issue: No ]
European Orgnisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 for cancer patients composed of 5 functional scales, 3 symptom scales, a global health status QOL scale, and six single items. Scores for each scale/item were calculated according to the questionnaire's scoring algorithm and range in 0 to 100, with high score represents high healthy level of functioning, high QOL or high level of symptomatology/problems. Change: Scores at cycle 1 minus scores at baseline.
Change from baseline in QOL will also be evaluated at cycle 6, 10, 15 and every 6 months during observation phase.
- Progression Free Survival (PFS) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]PFS based on radiographic criteria was defined as the time from registration to the time of radiographic progression. A confirmed progression was defined as one for which radiological evidence of a new lesion is found following CT and/or bone scans.
|Study Start Date:||January 2009|
|Study Completion Date:||March 2010|
|Primary Completion Date:||December 2009 (Final data collection date for primary outcome measure)|
Patients undergo standard leukapheresis to harvest peripheral blood mononuclear cells for dendritic cell vaccine preparation. Patients receive the APCC vaccine and autologous dendritic cells derived from CD14-positive myeloid peripheral blood cells ID on days 0, 14, and 28 and then every 28 days for up to 14 courses in the absence of disease progression or unacceptable toxicity.
Biological: allogeneic tumor cell vaccine
Given intradermallyBiological: therapeutic autologous dendritic cells
- Determine the proportion of patients with androgen-independent prostate cancer who are progression-free at one year after treatment with DC-APCC.
- Evaluate treatment toxicity.
- Evaluate time to prostate-cancer specific mortality.
- Evaluate progression-free survival.
- Evaluate time to PSA progression, and duration of PSA-based response.
- Evaluate quality of life of patients treated with this regimen.
OUTLINE: Patients undergo standard leukapheresis to harvest peripheral blood mononuclear cells for dendritic cell vaccine preparation and will receive the APCC vaccine and autologous dendritic cells derived from CD14-positive myeloid peripheral blood cells ID in every 2 weeks for the first 2 treatments (cycle 1 and 2), and then every 4 weeks therafter for up to 14 administrations in the absence of disease progression or unacceptable toxicity. The first four patients will be observed for four weeks following the third DC-APCC vaccination to assess toxicity, the enrollment of patients will continue if toxicity related events not present.
Patients undergo blood sample collection periodically for translational studies. Samples are measured for a number of immune parameters by quantifying T-cell and dentritic cell populations by analysis of surface marker molecules by flow cytometry, T-cell proliferation assay, non-specific cytokine release, lysate-specific cytokine release, and cytokine expression measured by cytometric bead array and qPCR.
Patients complete quality-of-life questionnaires periodically.
After completion of study treatment, patients are followed periodically for up to 3 years.
PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00814892
|United States, Minnesota|
|Mayo Clinic Cancer Center|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Manish Kohli, MD||Mayo Clinic|