Clinical trial NCT00060528
Conditions: Prostatic Neoplasms
Keywords: Immunotherapy Cytokines Immune Assays Prostate Cancer
Sponsor: National Cancer Institute (NCI)
Start date: 2003-05-22; Completion date: 2009-06-08
Enrollment: 32 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Background:

" Adenocarcinoma of the prostate is the most common cancer diagnosis in American males and follows lung cancer as the leading cause of cancer death.

" Vaccine strategies represent a novel therapeutic approach in the treatment for prostate cancer. One potential target for a prostate cancer vaccine is prostatic specific antigen (PSA), due to its restricted expression on prostate cancer and normal prostatic epithelial cells.

Objectives:

" The primary objective is to determine the impact of granulocyte-macrophage colony stimulating factor (GM-CSF) and recombinant fowlpox granulocyte-macrophage colony stimulating factor (rF-GM-CSF) on the immunologic response in patients treated with these vaccines.

" Secondary - to determine the change in prostatic specific antigen (PSA)-specific T cells in patients treated with these vaccines using enzyme linked immunosorbent spot (ELISPOT) assay analysis.

" To document any objective anti-tumor responses that may occur.

Eligibility:

" Patients must have androgen insensitive metastatic prostate cancer.

" All patients will have received and progressed on hormonal therapy.

" Must have objective evidence of metastasis or relapsing local disease. Therefore, must have a rising PSA and at least one of the following: positive bone scan, palpable disease, or positive imaging studies.

" Must have a life expectancy of more than 6 months and Eastern Cooperative Oncology Group (ECOG) status of 0 to 2.

"Patients must be human leukocyte antigen serotype within HLA-A A serotype group (HLA-A2+).

" Granulocyte count greater than or equal to 1,500/mm\^3, Platelet greater than or equal to 100,000/mm\^3, hemoglobin (Hgb) greater than or equal to 10Gm/dL, Lymphocyte count greater than or equal to 500/mm\^3 ;Bilirubin less than 1.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5x upper limit of normal (ULN),Creatinine Clearance greater than or equal to 60

" No significant cardiac disease, no significant pulmonary disease, no serious inter-current medical illness.

Design:

" Cohorts three, four and five will provide safety data combining cohort two with rGM-CSF as well as two doses of rFGM-CSF respectively.

"This study will be conducted as a small, randomized pilot study to compare the immunologic effects of the above vaccine strategy alone, with recombinant granulocyte-macrophage colony stimulating factor (GM-CSF), or with either of 2 doses of fowlpox-GM-CSF.

"This study will consist of 4 randomized arms of 8 patients each, all of whom are HLA-A2+.

The maximum accrual to the trial should be 62.

Detailed description:
Background:

* Adenocarcinoma of the prostate is the most common cancer diagnosis in American males and follows lung cancer as the leading cause of cancer death.
* Vaccine strategies represent a novel therapeutic approach in the treatment for prostate cancer. One potential target for a prostate cancer vaccine is prostatic specific antigen (PSA), due to its restricted expression on prostate cancer and normal prostatic epithelial cells.

Objectives:

* The primary objective is to determine the impact of granulocyte-macrophage colony stimulating factor (GM-CSF) and recombinant fowlpox granulocyte-macrophage colony stimulating factor (rF-GM-CSF) on the immunologic response in patients treated with these vaccines.
* Secondary - to determine the change in prostatic specific antigen (PSA)-specific T cells in patients treated with these vaccines using enzyme linked immunosorbent spot (ELISPOT) assay analysis.
* To document any objective anti-tumor responses that may occur.

Eligibility:

* Patients must have androgen insensitive metastatic prostate cancer.
* All patients will have received and progressed on hormonal therapy.
* Must have objective evidence of metastasis or relapsing local disease. Therefore, must have a rising PSA and at least one of the following: positive bone scan, palpable disease, or positive imaging studies.
* Must have a life expectancy of more than 6 months and the Eastern Cooperative Oncology Group (ECOG) status of 0 to 2.
* Patients must be HLA-A2+.
* Granulocyte count greater than or equal to 1,500/mm\^3, Platelet greater than or equal to 100,000/mm\^3, hemoglobin (Hgb) greater than or equal to 10Gm/dL, Lymphocyte count greater than or equal to 500/mm\^3; Bilirubin less than 1.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5x upper limit of normal (ULN),Creatinine Clearance greater than or equal to 60
* No significant cardiac disease, no significant pulmonary disease, no serious inter-current medical illness.

Design:

* Cohorts three, four and five will provide safety data combining cohort two with rGM-CSF as well as two doses of rFGM-CSF respectively.
* This study will be conducted as a small, randomized pilot study to compare the immunologic effects of the above vaccine strategy alone, with recombinant GM-CSF, or with either of 2 doses of fowlpox-GM-CSF.
* This study will consist of 4 randomized arms of 8 patients each, all of whom are HLA-A2+.

Arms: arm 1: No granulocyte macrophage colony stimulating factor (GM-CSF) was given arm 2: Recombinant human GM-CSF (Sargramostim) was administered at 100mcg/day on days 1-4 following each vaccine. Given subcutaneously (s.c.) at site of vaccine. arm 3: recombinant fowlpox GM-CSF was given on day one at 10\^7 in last two arms. Given subcutaneously (s.c.) at site of vaccine. arm 4: recombinant fowlpox GM-CSF was given on day one at 10\^8 in last two arms. Given subcutaneously (s.c.) at site of vaccine.
Interventions: intervention 1: Recombinant Fowlpox-GM-CSF intervention 2: Recombinant Fowlpox-PSA (L155)-TRICOM (PROSTVAC-F/TRICOM) intervention 3: Recombinant Vaccinia-PSA (L155)-TRICOM (PROSTVAC-V/TRICOM) intervention 4: Recombinant Human GM-CSF
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol documents: