Phase II Study of Active Immunotherapy With Mature, Human Telomerase Reverse Transcriptase Messenger RNA -Transfected, Autologous Dendritic Cells (DC) Administered In A Prime-Boost Format to Subjects With Metastatic Prostate Cancer
18 Years
N/A
Male
Metastatic Prostate Cancer
Trial Information
Phase II Study of Active Immunotherapy With Mature, Human Telomerase Reverse Transcriptase Messenger RNA -Transfected, Autologous Dendritic Cells (DC) Administered In A Prime-Boost Format to Subjects With Metastatic Prostate Cancer
Primary objectives of trial include to evaluate the safety and biologic efficacy of hTERT
mRNA transfected dendritic cells (DC), applied in a prime-boost format, to stimulate
hTERT-specific CD4+ and CD8+ T-cell responses in subjects with metastatic prostate cancer.
Secondary objectives include estimating objective clinical response, the duration of such
responses, progression-free survival and overall survival among all subjects. The hTERT
mRNA-transfected DC vaccine platform has previously been studied in several phase I/II
trials and has demonstrated safety and bioactivity in subjects with metastatic prostate and
renal cell carcinomas. The objective of this trial is to enhance the observed bioactivity of
the vaccine by using a prime-boost strategy. This is an open label, uncontrolled safety and
efficacy study. Subjects with metastatic prostate cancer will be eligible for this study and
will receive 1x107 cells administered ID at study week 1,2,3,4,5, and 6 (Prime). Thereafter,
subjects will be randomized with equal probability to receive either 5x106 cells
administered ID at study week 10 followed by monthly immunizations (Treatment arm A) or
1x107 cells administered ID at study week 10 followed by monthly immunizations (Treatment
arm B). The safety, biologic and clinical efficacy of each regimen will be analyzed. The
study will be solely conducted at the University of Florida in Gainesville, FL. Subjects
will be recruited through the oncology clinics of the Departments of Urology and Radiation
Oncology. The vaccine will be manufactured in a dedicated GMP-compliant cell production
facility located on the 4th floor of the Cancer Genetics Research Institute. Immunological
testing will be performed in the Immunological Monitoring Core laboratory of the Department
of Urology using standardized assay systems. Subjects with histologically or clinically
confirmed metastatic prostate cancer (stages pT1-4, N0-3, M+) are eligible for this study.
Subjects treated with medical hormone ablative therapy (LHRH analogues or estrogens) should
continue to receive LHRH analogues only. In subjects receiving nonsteroidal medical hormonal
treatment (i.e. flutamide or bicalutamide) and who are experiencing a rising PSA, a 4 week
period of observation will be required following the discontinuation of the nonsteroidal
antiandrogen prior to study entry. Subjects will be excluded from study if they have
received chemotherapy or other forms of immunotherapy in the 4 weeks prior to study entry.
They must not have a history of autoimmune disease, serious intercurrent chronic or acute
illness, pulmonary disease, active hepatitis, serologic evidence for HIV, or be receiving
corticosteroid or immunosuppressive therapy. All subjects must be older than 18 years. This
is a randomized phase II clinical trial, in which up to 36 subjects will be randomized with
equal probability to one of the two treatment arms. The objective of this trial is to decide
which of the two treatment regimens should be selected for further testing. Hence, the
primary objective of this trial is to select the arm with the highest biologic response and
the first ranked arm will be selected for further study in a larger efficacy trial.
Inclusion Criteria:
Subjects must have histologically or clinically confirmed adenocarcinoma of the prostate
with either:
- metastatic prostate adenocarcinoma, Stage (T1-4, N+, M0) or (T1-4, N0-3, M+) OR
- two documented rising PSA levels while maintained on LHRH analogues.
- Subjects who are receiving nonsteroidal antiandrogen therapy must discontinue
therapy for 4 weeks prior to study entry.
- Karnofsky Performance Status (KPS) greater than or equal to 80%
- Age ≥ 18 years
- Adequate hematologic function with:
- WBC ≥ 3000 mm3
- hemoglobin ≥ 9 mg/dl
- platelets ≥ 100,000/mm3
• Adequate renal and hepatic function with:
- serum creatinine < 2.5 mg/dl
- bilirubin < 2.0 mg/dl
• Adequate coagulation parameters with:
- Prothrombin Time < 1.5 x control
- Partial thromboplastin time < 1.5 x control • Ability to understand and provide
signed inform consent that fulfills Institutional Review Board guidelines.
Exclusion Criteria:
- Subjects who have received radiation therapy within 4 weeks of pretreatment
evaluation. (There must be at least 12 weeks if prior therapy included 89-Strontium
between any prior therapy and study entry.)
- Subjects who have received chemotherapy or biologic regimens within 4 weeks of
pretreatment evaluation.
- Subjects who have received immunotherapy within 4 weeks of pretreatment evaluation.
- Subjects who have not recovered from radiation, chemotherapy, or immunotherapy
toxicities.
- Subjects with either previously irradiated or new CNS (central nervous system)
metastases. (Pre-enrollment head CT is not required.)
- Subjects with a history of autoimmune disease such as, but not restricted to,
inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis,
scleroderma, or multiple sclerosis.
- Subjects with serious intercurrent chronic or acute illness such as pulmonary (asthma
or COPD) or cardiac (NYHA class III or IV) or hepatic disease or other illness
considered by the P.I. to constitute an unwarranted high risk for investigational
drug treatment.
- Medical or psychological impediment to probable compliance with the protocol.
- Concurrent second malignancy other than non-melanoma skin cancer, or controlled
superficial bladder cancer. In the event of prior malignancies treated surgically,
the subject must be considered NED (no evidence of disease) for a minimum of 3 years
prior to enrollment.
- Presence of an active acute or chronic infection, including symptomatic urinary tract
infection, HIV (as determined by ELISA and confirmed by Western Blot) or viral
hepatitis (as determined by HBsAg and Hepatitis C serology).
- Subjects on steroid therapy (or other immunosuppressive agents such as azathioprine
or cyclosporine A) are excluded on the basis of potential immune suppression.
Subjects must have had 4 weeks of discontinuation of any steroid therapy prior to
enrollment.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
The primary objective of this trial is to evaluate the safety of a boosting regimen using immunizations with two distinct doses of hTERT mRNA DC.
Outcome Description:
All subjects will receive 1x107 cells administered ID at study weeks 1, 2, 3, 4, 5, and 6. Subjects will subsequently be randomized with equal probability to receive hTERT mRNA DC at study weeks 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 at one of the following doses: 5x106 cells per infusion administered ID (Treatment arm A). 1x107 cells per infusion administered ID (Treatment arm B).
Outcome Time Frame:
50 Weeks
Safety Issue:
Yes
Authority:
United States: Food and Drug Administration
Study ID:
LAMP hTERT DC Vaccine
NCT ID:
NCT01153113
Start Date:
January 2008
Completion Date:
December 2010
Related Keywords:
- Metastatic Prostate Cancer
- adenocarcinoma of the prostate
- metastatic prostate adenocarcinoma, Stage (T1-4, N+, M0) or (T1-4, N0-3, M+)
- rising PSA levels while maintained on LHRH analogues
- Prostatic Neoplasms
Name | Location |
|---|
