Sequential Vaccinations in Prostate Cancer Patients

Phase 1

Completed

Conditions: Prostatic Neoplasms

Interventions: Drug: Recombinant Fowlpox-PSA (L155)-TRICOM (PROSTVAC-F/TRICOM)
Drug: Recombinant Vaccinia-PSA (L155)-TRICOM (PROSTVAC-V/TRICOM)
Drug: Recombinant Fowlpox-GM-CSF
Drug: Recombinant Human GM-CSF

Registration Number: NCT00060528

Lead Sponsor: National Cancer Institute (NCI)

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+.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 32

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
no GM	Recombinant Fowlpox-PSA (L155)-TRICOM (PROSTVAC-F/TRICOM)	No granulocyte macrophage colony stimulating factor (GM-CSF) was given
Rec-hGM	Recombinant Vaccinia-PSA (L155)-TRICOM (PROSTVAC-V/TRICOM)	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.
Rec-hGM	Recombinant Human GM-CSF	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.
rF-GM (10^7pfu)	Recombinant Fowlpox-GM-CSF	recombinant fowlpox GM-CSF was given on day one at 10\^7 in last two arms. Given subcutaneously (s.c.) at site of vaccine.
rF-GM (10^7pfu)	Recombinant Fowlpox-PSA (L155)-TRICOM (PROSTVAC-F/TRICOM)	recombinant fowlpox GM-CSF was given on day one at 10\^7 in last two arms. Given subcutaneously (s.c.) at site of vaccine.
rF-GM (10^8)	Recombinant Fowlpox-GM-CSF	recombinant fowlpox GM-CSF was given on day one at 10\^8 in last two arms. Given subcutaneously (s.c.) at site of vaccine.
rF-GM (10^8)	Recombinant Fowlpox-PSA (L155)-TRICOM (PROSTVAC-F/TRICOM)	recombinant fowlpox GM-CSF was given on day one at 10\^8 in last two arms. Given subcutaneously (s.c.) at site of vaccine.
rF-GM (10^8)	Recombinant Human GM-CSF	recombinant fowlpox GM-CSF was given on day one at 10\^8 in last two arms. Given subcutaneously (s.c.) at site of vaccine.
rF-GM (10^7pfu)	Recombinant Human GM-CSF	recombinant fowlpox GM-CSF was given on day one at 10\^7 in last two arms. Given subcutaneously (s.c.) at site of vaccine.

Primary Outcome Measures

Name	Time	Method
Number of Participants With an Immune Response	48 months	Immune response is defined as an enhanced PSA specific T-cell immune response greater than or equal to twofold post-vaccination. Peripheral blood mononuclear cells (PBMCs) were collected by apheresis prior to treatment with vaccination and after approximately three months of therapy.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With an Objective Response	53 months	Objective response is determined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria defined as: measurable disease (at least one measurable lesion), measurable lesions (lesions that can be accurately measured in at least one dimension with longest diameter \>/= 20 mm using conventional techniques or \>/= 10 mm with spiral CT scan. Non-measurable lesions (all other lesions, including small lesions (longest diameter \< 20 mm with conventional techniques or \< 10 mm with spiral CT scan), i.e. bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusion...
Overall Survival	50 months	Overall survival is defined as the date of on-study to the date of death from any cause or last follow-up.
Percent of Participants With a Decrease (i.e. Greater Than or Equal to 30%) in PSA Levels	53 months	PSA level at the time treatment is initiated compared to the PSA level at Day 85 and monthly thereafter while the patient continues on trial)
The Number of Participants With Adverse Events	77.5 months	Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module.