Sequential Vaccinations in Prostate Cancer Patients

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00060528
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 4
• Actual Duration (Months): 72.6
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms	Drug: Recombinant Fowlpox-GM-CSF; Drug: Recombinant Fowlpox-PSA (L155)-TRICOM (PROSTVAC-F/TRICOM); Drug: Recombinant Vaccinia-PSA (L155)-TRICOM (PROSTVAC-V/TRICOM); Drug: Recombinant Human GM-CSF	Phase 1/Phase 2

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+.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Pilot Study of Sequential Vaccinations With rFowlpox-PSA (L155)-TRICOM (PROSTVAC-F/TRICOM) Alone, or in Combination With rVaccinia-PSA (L155)-TRICOM (PROSTVAC-V/TRICOM), and the Role of GM-CSF, in Men With Prostate Cancer
• Actual Study Start Date: May 22, 2003
• Actual Primary Completion Date: Mar 7, 2006
• Actual Study Completion Date: Jun 8, 2009

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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)

2. 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...

3. 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.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

Patients must have histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI), or National Naval Medical Center (NNMC) prior to starting this study.

If no pathologic specimen is available to the NCI or NNMC, patients may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.

Patients must have androgen insensitive metastatic prostate cancer.

Progression must be documented by at least one of the following parameters:

1. All patients must have received standard of care (hormonal) treatment before entering the trial.

2. All patients will have received and progressed on hormonal therapy for metastatic prostate carcinoma.

3. All subjects must have objective evidence of metastasis or relapsing local disease to be eligible for this Phase I trial; therefore, they must have a rising PSA and at least one of the following: positive bone scan, palpable disease, or positive imaging studies, as defined below.

1. Two consecutively rising prostatic specific antigen (PSA) levels, separated by at least 1 week, with at least one measurement that is 50% above the nadir reached after the last therapeutic maneuver (as long as the last measurement is 5 ng/ml or greater), and

1. At least one lesion consistent with metastatic cancer on Technetium (Tc)-99 whole body scintigraphy, and/or

2. Soft-tissue metastases as measured by appropriate modalities (i.e., imaging, palpation).

Patients must have a life expectancy of more than 6 months.

Patients must have a performance status of 0 to 2 according to the Eastern Cooperative Oncology Group (ECOG) criteria.

Patients must have recovered from any acute toxicity related to prior therapy, including surgery, and radiation (treatment must have been completed at least 4 weeks prior to being eligible for the study).

Patients who are responding to hormonal therapy are not eligible until evidence of disease progression.

Hematological eligibility parameters (within 16 days of starting therapy):

• Granulocyte count greater than or equal to 1,500/mm^3

• Platelet count greater than or equal to 100,000/mm^3

• Lymphocyte count greater than or equal to 500/mm^3

• Hemoglobin (Hgb) greater than or equal to 10 Gm/dL

Biochemical eligibility parameters (within 16 days of starting therapy):

1. A 24-hour urine collection for baseline to measure creatinine clearance (CrCl), protein and electrolytes.

CrCl greater than 60, proteinuria less than 1000 milligrams per 24 hours, less than or equal to Grade 1 (NCI-common toxicity criteria (CTC) version 2.0) proteinuria, Grade 0 hematuria, and no abnormal sediment.

Grade 0 creatinine.

Patients must have serum creatinine within normal limits.

Any abnormalities in the sediment or the presence of hematuria without a likely underlying cause should prompt the investigator to consider an evaluation by a nephrologist for evidence of underlying renal pathology. Patients may be eligible if the underlying cause of the abnormality is determined to be non-renal.

1. Hepatic function: Bilirubin less than 1.5 mg/dl,

aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 times upper limit of normal.

1. Patients must be test negative for human immunodeficiency virus (HIV), Hepatitis B and

Patients must not have other active malignancies within the past 2 years (with the exception of non-melanoma skin cancers or carcinoma in situ of the bladder) or life threatening illnesses.

Patients must be willing to travel to the National Institutes of Health (NIH) for follow-up visits.

Patients must be greater than or equal to 18 years of age.

All patients who have received prior vaccination with vaccinia virus (for smallpox immunization) must not have a history of allergy or untoward reaction to the vaccine. Since vaccinia immunoglobulin (VIG) is available from the Centers for Disease Control (CDC), prior vaccinia vaccination as a safety precaution is no longer required.

Patients must understand and sign informed consent that explains the neoplastic nature of their disease, the procedures to be followed, the experimental nature of the treatment, alternative treatments, potential risks and toxicities, and the voluntary nature of participation.

Patients must not have received the following chemotherapeutic agents for cancer within 3 years of enrolling on study: docetaxel, paclitaxel, doxorubicin, cisplatinum, carboplatinum, mitoxantrone, estramustine, cyclophosphamide, irinotecan, topotecan.

Patients must not have received prior PSA vaccine therapy.

Patients will tested for human leukocyte antigen serotype within HLA-A A serotype group (HLA-A2). This test may be drawn by the patient's referring physician at the time of referral (see Appendix C, HLA-typing consent). This consent will be mailed to the patient and discussed with patient. The signed consent will be signed with a witness, then mailed to the assigned research nurse at the NIH Clinical Center. These patients must have measurable disease on computed tomography (CT), magnetic resonance imaging (MRI), or bone scan.

The effects of the study agents used in this protocol on the developing human fetus are unknown. For this reason men must agree to use adequate contraception prior to study entry and for the duration of study participation.

INCLUSION CRITERIA:

Patients must have histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI), or National Naval Medical Center (NNMC) prior to starting this study. If no pathologic specimen is available to the NCI or NNMC, patients may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.

1. All patients will have received and progressed on hormonal therapy for metastatic prostate carcinoma.

2. All subjects must have objective evidence of metastasis or relapsing local disease to be eligible; therefore, they must have a rising PSA and at least one of the following: positive bone scan, palpable disease, or positive imaging studies, as defined below.

1. Two consecutively rising PSA levels, separated by at least 1 week, with at least one measurement that is 50% above the

nadir reached after the last therapeutic maneuver (as long as the last measurement is 5 ng/ml or greater), and

1. At least one lesion consistent with metastatic cancer on Technetium (Tc)-99 whole body scintigraphy, and/or

2. Soft-tissue metastases as measured by appropriate modalities (i.e., imaging, palpation).

Patients must have a life expectancy of more than 6 months.

Patients must have a performance status of 0 to 2 according to the ECOG criteria.

Patients must have recovered from any acute toxicity related to prior therapy, including surgery, and radiation (treatment must have been completed at least 4 weeks prior to being eligible for the study).

Hematological eligibility parameters (within 16 days of starting therapy):

• Granulocyte count greater than or equal to 1,500/mm^3

• Platelet count greater than or equal to 100,000/mm^3

• Lymphocyte count greater than or equal to 500/mm^3

• Hgb greater than or equal to 10 Gm/dL

Biochemical eligibility parameters (within 16 days of starting therapy):

1. A 24-hour urine collection for baseline to measure creatinine clearance (CrCl), protein and electrolytes.

CrCl greater than 60

proteinuria less than 1000 milligrams per 24 hours, less than or equal to Grade 1 (NCI-Common Toxicity Criteria (CTC) version 2.0) proteinuria, Grade 0 hematuria, and no abnormal sediment.

Grade 0 creatinine.

Patients must have serum creatinine within normal limits.

Any abnormalities in the sediment or the presence of hematuria without a likely underlying cause should prompt the investigator to consider an evaluation by a nephrologist for evidence of underlying renal pathology. Patients may be eligible if the underlying cause of the abnormality is determined to be non-renal.

1. Hepatic function: Bilirubin less than 1.5 mg/dl,

AST and ALT less than 2.5 times upper limit of normal.

1. Patients must test negative for HIV, Hepatitis B and C.

Patients must not have other active malignancies within the past 2 years (with the exception of non-melanoma skin cancers or carcinoma in situ of the bladder) or life threatening illnesses.

Patients must be willing to travel to the NIH for follow-up visits.

Patients must be greater than or equal to 18 years of age.

All patients who have received prior vaccination with vaccinia virus (for smallpox immunization) must not have a history of allergy or untoward reaction to the vaccine. Since vaccinia immunoglobulin (VIG) is available from the CDC, prior vaccinia vaccination as a safety precaution is no longer required.

Patients must understand and sign informed consent that explains the neoplastic nature of their disease, the procedures to be followed, the experimental nature of the treatment, alternative treatments, potential risks and toxicities, and the voluntary nature of participation.

Patients have not received the following chemotherapeutic agents for cancer within 3 years of enrolling on study: docetaxel, paclitaxel, doxorubicin, cisplatinum, carboplatinum, mitoxantrone, estramustine, cyclophosphamide, irinotecan, topotecan.

Patients have not received prior PSA vaccine therapy.

All patients will tested for HLA-A2. Patients must be HLA-A2+. This test may be drawn by the patient's referring physician at the time of referral (see Appendix C, HLA-typing consent). This consent will be mailed to the patient and discussed with patient. The signed consent will be signed with a witness, then mailed to the assigned research nurse at the National Institutes of Health (NIH) Clinical Center. These patients must have measurable disease on computed tomography (CT), magnetic resonance imaging (MRI), or bone scan.

The effects of the study agents used in this protocol on the developing human fetus are unknown. For this reason men must agree to use adequate contraception prior to study entry and for the duration of study participation.

EXCLUSION CRITERIA:

Prior splenectomy.

Concurrent steroid use, except topical steroids or inhaled steroid use.

The recombinant vaccinia vaccine should not be administered if the following apply to either recipients or, for at least 3 weeks after vaccination, their close household contacts:

persons with active or a history of eczema or other eczematoid skin disorders; those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne or other open rashes or wounds) until condition resolves; pregnant or nursing women; children under 5 years of age; and immunodeficient or immunosuppressed persons (by disease or therapy), including HIV infection.

Close household contacts are those who share housing or have close physical contact.

Patients with known allergy to eggs.

Other serious intercurrent illness.

Patients with brain metastases.

Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment) or New York Heart Association class II-IV congestive heart failure.

Patients on antiandrogen therapy must undergo antiandrogen withdrawal for at least 4 weeks and still show evidence of a rising PSA.

Following treatment with bicalutamide, patients must undergo withdrawal for at least 6 weeks and still show evidence of a rising PSA.

Prior treatments with vaccine expressing PSA are NOT eligible.

Patients with significant autoimmune disease that is active or potentially life threatening if activated.

Patients with clinically significant cardiomyopathy requiring treatment should be excluded from protocol eligibility at this time.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: James L Gulley, M.D., National Cancer Institute, National Institutes of Health

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Medline Plus
• Drug Information Portal
• U.S. FDA Resources

Publications

• Correale P, Walmsley K, Nieroda C, Zaremba S, Zhu M, Schlom J, Tsang KY. In vitro generation of human cytotoxic T lymphocytes specific for peptides derived from prostate-specific antigen. J Natl Cancer Inst. 1997 Feb 19;89(4):293-300.
• Gulley JL, Arlen PM, Madan RA, Tsang KY, Pazdur MP, Skarupa L, Jones JL, Poole DJ, Higgins JP, Hodge JW, Cereda V, Vergati M, Steinberg SM, Halabi S, Jones E, Chen C, Parnes H, Wright JJ, Dahut WL, Schlom J. Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer. Cancer Immunol Immunother. 2010 May;59(5):663-74. doi: 10.1007/s00262-009-0782-8. Epub 2009 Nov 5.
• Kim JW, Madan RA, Gulley JL. Initial PSA oscillations precede prolonged stable disease in a patient treated with a therapeutic cancer vaccine. Clin Genitourin Cancer. 2012 Mar;10(1):43-6. doi: 10.1016/j.clgc.2011.09.003. Epub 2011 Oct 21.
• Smith HA, Maricque BB, Eberhardt J, Petersen B, Gulley JL, Schlom J, McNeel DG. IgG responses to tissue-associated antigens as biomarkers of immunological treatment efficacy. J Biomed Biotechnol. 2011;2011:454861. doi: 10.1155/2011/454861. Epub 2010 Dec 19.
• Stein WD, Gulley JL, Schlom J, Madan RA, Dahut W, Figg WD, Ning YM, Arlen PM, Price D, Bates SE, Fojo T. Tumor regression and growth rates determined in five intramural NCI prostate cancer trials: the growth rate constant as an indicator of therapeutic efficacy. Clin Cancer Res. 2011 Feb 15;17(4):907-17. doi: 10.1158/1078-0432.CCR-10-1762. Epub 2010 Nov 24.
• Vergati M, Cereda V, Madan RA, Gulley JL, Huen NY, Rogers CJ, Hance KW, Arlen PM, Schlom J, Tsang KY. Analysis of circulating regulatory T cells in patients with metastatic prostate cancer pre- versus post-vaccination. Cancer Immunol Immunother. 2011 Feb;60(2):197-206. doi: 10.1007/s00262-010-0927-9. Epub 2010 Oct 26.
• Yokokawa J, Cereda V, Remondo C, Gulley JL, Arlen PM, Schlom J, Tsang KY. Enhanced functionality of CD4+CD25(high)FoxP3+ regulatory T cells in the peripheral blood of patients with prostate cancer. Clin Cancer Res. 2008 Feb 15;14(4):1032-40. doi: 10.1158/1078-0432.CCR-07-2056.

• Responsible Party: James Gulley, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT00060528
• Other Study ID Numbers: 030176; 03-C-0176; NCT00062153
• First Posted: May 7, 2003
• Last Update Posted: Oct 26, 2017
• Last Verified: Sep 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by James Gulley, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC): Immunotherapy; Cytokines; Immune Assays; Prostate Cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Metronidazole; Molgramostim; Sargramostim

Study Results

Participant Flow

Recruitment Details	32 patients were accrued to the phase II portion of the study

Arm/Group Title	no GM	Rec-hGM	rF-GM (10^7pfu)	rF-GM (10^8)
Arm/Group Description	Vaccine subcutaneously with no GM	Vaccine subcutaneously with Rec-hGM sucutaneously (daily x 4/vaccine)	Vaccine subcutaneously with rF-GM (10^7pfu) subcutaneously x1	Vaccine subcutaneously with rF-GM (10^8) subcutaneously x1
Period Title: Overall Study
STARTED	8	9	7	8
COMPLETED	8	9	7	8
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Prostate Cancer Patients
Arm/Group Description	Progressive Metastatic Castration Resistant Prostate Cancer
Overall Participants	32
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	16 50%
>=65 years	16 50%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.1 (8.85)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	32 100%
Region of Enrollment (Count of Participants)
United States	32 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With an Immune Response
Description	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.
Time Frame	48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	No GM	Rec-hGM	rF-GM (10^7pfu),	rF-GM (10^8)
Arm/Group Description	Vaccine subcutaneously with no GM	Vaccine subcutaneously with Rec-hGM sucutaneously (daily x 4/vaccine)	Vaccine subcutaneously with rF-GM (10^7pfu) subcutaneously x1	Vaccine subcutaneously with rF-GM (10^8) subcutaneously x1
Measure Participants	8	6	7	8
Count of Participants [Participants]	2 6.3%	4 NaN	4 NaN	3 NaN

2. Secondary Outcome

Title	Percent of Participants With a Decrease (i.e. Greater Than or Equal to 30%) in PSA Levels
Description	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)
Time Frame	53 months

Outcome Measure Data

Analysis Population Description

PSA was taken at multiple time points and proportion of patients (pts) who had a decrease in PSA of at least 30% was reported. This is standard reporting procedures for tumor markers (proportion of patients with a response);similar to RECIST reporting where there may be multiple scans obtained but one reports the proportion of pts with a response

Arm/Group Title	Phase 2
Arm/Group Description	Phase 2 patients are randomized between 4 arms:e.g. No GM, Rec-hGM, rF-GM (10^7pfu), rF-GM (10^8) with efficacy and immunological response as a primary endpoint.
Measure Participants	32
Number [Percentage of participants]	15.6 48.8%

3. Secondary Outcome

Title	Number of Participants With an Objective Response
Description	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...
Time Frame	53 months

Outcome Measure Data

Analysis Population Description

All 12 participants with measurable disease were evaluated.

Arm/Group Title	Phase 2
Arm/Group Description	Phase 2 patients are randomized between 4 arms: e.g. No GM, Rec-hGM, rF-GM (10^7pfu), rF-GM (10^8) with efficacy and immunological response as a primary endpoint.
Measure Participants	12
Count of Participants [Participants]	0 0%

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the date of on-study to the date of death from any cause or last follow-up.
Time Frame	50 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 2
Arm/Group Description	Phase 2 patients are randomized between 4 arms: e.g. No GM, Rec-hGM, rF-GM (10^7pfu), rF-GM (10^8)with efficacy and immunological response as a primary endpoint.
Measure Participants	32
Median (Full Range) [Months]	26.6

5. Secondary Outcome

Title	The Number of Participants With Adverse Events
Description	Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
Time Frame	77.5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 2
Arm/Group Description	Phase 2 patients are randomized between 4 arms: e.g. No GM, Rec-hGM, rF-GM (10^7pfu), rF-GM (10^8)with efficacy and immunological response as a primary endpoint.
Measure Participants	32
Count of Participants [Participants]	32 100%

Adverse Events

Time Frame	77.5 months
Arm/Group Title	no GM		Rec-hGM		rF-GM (10^7pfu)		rF-GM (10^8)
Arm/Group Description	Vaccine subcutaneously with no GM		Vaccine subcutaneously with Rec-hGM sucutaneously (daily x 4/vaccine)		Vaccine subcutaneously with rF-GM (10^7pfu) subcutaneously x1		Vaccine subcutaneously with rF-GM (10^8) subcutaneously x1
All Cause Mortality
	no GM		Rec-hGM		rF-GM (10^7pfu)		rF-GM (10^8)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/9 (0%)		0/7 (0%)		0/8 (0%)
Serious Adverse Events
	no GM		Rec-hGM		rF-GM (10^7pfu)		rF-GM (10^8)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		3/9 (33.3%)		2/7 (28.6%)		3/8 (37.5%)
Blood and lymphatic system disorders
Hemoglobin	0/8 (0%)	0	1/9 (11.1%)	1	0/7 (0%)	0	1/8 (12.5%)	1
Cardiac disorders
Supraventricular arrhythmias (supraventricular tachycardia (SVT)/atrial fibrillation/flutter)	1/8 (12.5%)	1	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Gastrointestinal disorders
Anorexia	0/8 (0%)	0	1/9 (11.1%)	1	1/7 (14.3%)	1	0/8 (0%)	0
Constipation	0/8 (0%)	0	1/9 (11.1%)	1	0/7 (0%)	0	0/8 (0%)	0
Dehydration	0/8 (0%)	0	1/9 (11.1%)	1	1/7 (14.3%)	1	0/8 (0%)	0
Diarrhea patients without colostomy	0/8 (0%)	0	1/9 (11.1%)	1	0/7 (0%)	0	0/8 (0%)	0
Nausea	0/8 (0%)	0	1/9 (11.1%)	1	0/7 (0%)	0	1/8 (12.5%)	1
General disorders
Constitutional Symptoms-Other (Specify_)	0/8 (0%)	0	1/9 (11.1%)	1	0/7 (0%)	0	0/8 (0%)	0
Musculoskeletal and connective tissue disorders
Bone pain	0/8 (0%)	0	2/9 (22.2%)	2	0/7 (0%)	0	0/8 (0%)	0
Myalgia (muscle pain)	0/8 (0%)	0	0/9 (0%)	0	1/7 (14.3%)	1	2/8 (25%)	3
Nervous system disorders
Mood alteration-depression	0/8 (0%)	0	1/9 (11.1%)	1	0/7 (0%)	0	0/8 (0%)	0
Other (Not Including Serious) Adverse Events
	no GM		Rec-hGM		rF-GM (10^7pfu)		rF-GM (10^8)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		9/9 (100%)		7/7 (100%)		8/8 (100%)
Blood and lymphatic system disorders
Lymphopenia	0/8 (0%)	0	2/9 (22.2%)	5	1/7 (14.3%)	1	1/8 (12.5%)	1
Leukocytes (total white blood cell (WBC))	1/8 (12.5%)	2	0/9 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1
Platelets	1/8 (12.5%)	1	1/9 (11.1%)	1	0/7 (0%)	0	1/8 (12.5%)	1
Partial thromboplastin time (PTT)	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1
Hematuria (in the absence of vaginal bleeding)	1/8 (12.5%)	2	0/9 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0
Hemoglobin	4/8 (50%)	7	4/9 (44.4%)	5	4/7 (57.1%)	5	7/8 (87.5%)	12
Cardiac disorders
Sinus tachycardia	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Vasovagal episode	1/8 (12.5%)	1	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Edema	2/8 (25%)	3	0/9 (0%)	0	2/7 (28.6%)	2	1/8 (12.5%)	1
Hypotension	1/8 (12.5%)	1	0/9 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1
Thrombosis/embolism	0/8 (0%)	0	0/9 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0
Ventricular arrhythmia (PVCs/bigeminy/trigeminy/ventricular tachycardia)	1/8 (12.5%)	1	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Hypertension	0/8 (0%)	0	1/9 (11.1%)	1	1/7 (14.3%)	1	0/8 (0%)	0
Congenital, familial and genetic disorders
Prothrombin time (PT)	1/8 (12.5%)	3	0/9 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0
Ear and labyrinth disorders
Inner ear/hearing	1/8 (12.5%)	1	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Earache (otalgia)	0/8 (0%)	0	1/9 (11.1%)	1	0/7 (0%)	0	0/8 (0%)	0
Epistaxis	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1
Gastrointestinal disorders
Vomiting	1/8 (12.5%)	1	1/9 (11.1%)	1	1/7 (14.3%)	2	1/8 (12.5%)	4
Diarrhea patients without colostomy	1/8 (12.5%)	2	1/9 (11.1%)	2	1/7 (14.3%)	3	1/8 (12.5%)	1
Nausea	2/8 (25%)	6	3/9 (33.3%)	5	3/7 (42.9%)	3	2/8 (25%)	2
Dysphagia, esophagitis, odonphagia (painful swallowing)	0/8 (0%)	0	0/9 (0%)	0	1/7 (14.3%)	1	1/8 (12.5%)	2
Mouth dryness	0/8 (0%)	0	0/9 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0
Dyspepsia/heartburn	0/8 (0%)	0	1/9 (11.1%)	1	1/7 (14.3%)	1	0/8 (0%)	0
Dehydration	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Anorexia	0/8 (0%)	0	1/9 (11.1%)	1	1/7 (14.3%)	2	1/8 (12.5%)	1
Diarrhea patients with a colostomy	0/8 (0%)	0	0/9 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0
General disorders
Fatigue (lethargy, malaise, asthenia)	4/8 (50%)	6	4/9 (44.4%)	9	2/7 (28.6%)	5	3/8 (37.5%)	3
Rigors, chills	1/8 (12.5%)	1	2/9 (22.2%)	5	2/7 (28.6%)	4	0/8 (0%)	0
Sweating (diaphoresis)	2/8 (25%)	2	1/9 (11.1%)	1	2/7 (28.6%)	2	2/8 (25%)	3
Weight loss	1/8 (12.5%)	1	0/9 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1
Sense of smell	0/8 (0%)	0	1/9 (11.1%)	1	0/7 (0%)	0	0/8 (0%)	0
Pain-Other (Specify_)	0/8 (0%)	0	1/9 (11.1%)	1	2/7 (28.6%)	4	0/8 (0%)	0
Syndromes-Other (Specify-flu like syndrome)	0/8 (0%)	0	0/9 (0%)	0	1/7 (14.3%)	2	0/8 (0%)	0
Fever (in the absence of neutropenia, where neutropenia is defined as AGC <1.0x10e9/L)	1/8 (12.5%)	1	3/9 (33.3%)	3	1/7 (14.3%)	2	2/8 (25%)	5
Hepatobiliary disorders
Hypoalbuminemia	4/8 (50%)	5	4/9 (44.4%)	6	5/7 (71.4%)	17	7/8 (87.5%)	9
SGPT (ALT) (serum glutamic pyruvic transaminase) (alanine aminotransferase)	3/8 (37.5%)	3	0/9 (0%)	0	3/7 (42.9%)	5	2/8 (25%)	2
SGOT (AST) (serum glutamic oxaloacetic transaminase) (aspartate aminotransferase)	5/8 (62.5%)	5	3/9 (33.3%)	4	5/7 (71.4%)	9	4/8 (50%)	5
Alkaline phosphatase	3/8 (37.5%)	3	3/9 (33.3%)	5	4/7 (57.1%)	5	3/8 (37.5%)	4
Bilirubin	1/8 (12.5%)	1	0/9 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1
Constipation	1/8 (12.5%)	1	1/9 (11.1%)	1	0/7 (0%)	0	1/8 (12.5%)	3
Immune system disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	4/8 (50%)	5	0/9 (0%)	0	3/7 (42.9%)	5	1/8 (12.5%)	2
Infections and infestations
Infection without neutropenia	2/8 (25%)	6	5/9 (55.6%)	5	2/7 (28.6%)	4	0/8 (0%)	0
Chest pain (non-cardiac and non-pleuritic)	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Infection without neutropenia	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	3/8 (37.5%)	14	7/9 (77.8%)	11	6/7 (85.7%)	13	3/8 (37.5%)	6
Bicarbonate	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	2/8 (25%)	2
Hypercalcemia	2/8 (25%)	2	1/9 (11.1%)	1	0/7 (0%)	0	0/8 (0%)	0
Hyperkalemia	0/8 (0%)	0	1/9 (11.1%)	1	1/7 (14.3%)	1	2/8 (25%)	2
Hypokalemia	2/8 (25%)	2	0/9 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1
Hyperuricemia	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Hypoglycemia	1/8 (12.5%)	1	0/9 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0
Hyponatremia	2/8 (25%)	2	2/9 (22.2%)	4	1/7 (14.3%)	1	1/8 (12.5%)	1
Hypophosphatemia	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	2/8 (25%)	2
Hypocalcemia	1/8 (12.5%)	2	1/9 (11.1%)	1	2/7 (28.6%)	2	1/8 (12.5%)	1
CPK (creatine phosphokinase)	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1
Hypomagnesemia	0/8 (0%)	0	0/9 (0%)	0	2/7 (28.6%)	2	0/8 (0%)	0
Bicarbonate	0/8 (0%)	0	1/9 (11.1%)	1	0/7 (0%)	0	0/8 (0%)	0
Hypercholesterolemia	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Bone pain	1/8 (12.5%)	2	2/9 (22.2%)	3	4/7 (57.1%)	5	2/8 (25%)	3
Myalgia (muscle pain)	4/8 (50%)	10	4/9 (44.4%)	5	5/7 (71.4%)	12	3/8 (37.5%)	5
Arthritis	0/8 (0%)	0	1/9 (11.1%)	2	0/7 (0%)	0	0/8 (0%)	0
Hypermagnesemia	1/8 (12.5%)	4	3/9 (33.3%)	3	2/7 (28.6%)	3	2/8 (25%)	3
Arthralgia (joint pain)	0/8 (0%)	0	1/9 (11.1%)	1	0/7 (0%)	0	0/8 (0%)	0
Muscle weakness (not due to neuropathy)	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Nervous system disorders
Dizziness/lightheadedness	2/8 (25%)	4	2/9 (22.2%)	4	1/7 (14.3%)	2	2/8 (25%)	6
Extrapyramidal/involuntary movement/restlessness	1/8 (12.5%)	1	0/9 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1
Mood alteration/depression	0/8 (0%)	0	0/9 (0%)	0	1/7 (14.3%)	1	1/8 (12.5%)	1
Insomnia	0/8 (0%)	0	1/9 (11.1%)	2	2/7 (28.6%)	2	0/8 (0%)	0
Mood alteration-anxiety, agitation	0/8 (0%)	0	0/9 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0
Neuropathy-sensory	0/8 (0%)	0	0/9 (0%)	0	1/7 (14.3%)	2	1/8 (12.5%)	1
Depressed level of consciousness	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1
Confusion	0/8 (0%)	0	1/9 (11.1%)	1	0/7 (0%)	0	0/8 (0%)	0
Psychiatric disorders
Syncope (fainting)	1/8 (12.5%)	1	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Renal and urinary disorders
Creatinine	3/8 (37.5%)	7	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Proteinuria	0/8 (0%)	0	1/9 (11.1%)	1	1/7 (14.3%)	1	0/8 (0%)	0
Urinary frequency/urgency	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Urinary retention	0/8 (0%)	0	0/9 (0%)	0	2/7 (28.6%)	2	0/8 (0%)	0
Dysuria (painful urination)	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Reproductive system and breast disorders
Abdominal pain or cramping	0/8 (0%)	0	2/9 (22.2%)	3	0/7 (0%)	0	0/8 (0%)	0
Pelvic pain	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Headache	0/8 (0%)	0	3/9 (33.3%)	4	1/7 (14.3%)	3	0/8 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	3/8 (37.5%)	4	1/9 (11.1%)	1	2/7 (28.6%)	3	1/8 (12.5%)	2
Pleuritic pain	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Apnea	0/8 (0%)	0	0/9 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0
Dyspnea (shortness of breath)	1/8 (12.5%)	1	0/9 (0%)	0	1/7 (14.3%)	2	0/8 (0%)	0
Skin and subcutaneous tissue disorders
Bruising (in absence of grade 3 or 4 thrombocytopenia)	0/8 (0%)	0	1/9 (11.1%)	1	1/7 (14.3%)	2	0/8 (0%)	0
Injection site reaction	7/8 (87.5%)	30	8/9 (88.9%)	20	6/7 (85.7%)	40	7/8 (87.5%)	21
Hand-foot skin reaction	1/8 (12.5%)	1	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Pruritis	1/8 (12.5%)	1	2/9 (22.2%)	2	1/7 (14.3%)	1	0/8 (0%)	0
Urticaria (hives, welts, wheals)	1/8 (12.5%)	3	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Wound-non-infectious	2/8 (25%)	3	0/9 (0%)	0	0/7 (0%)	0	0/8 (0%)	0
Dermatology/Skin-Other (Specify_)	1/8 (12.5%)	1	0/9 (0%)	0	1/7 (14.3%)	1	1/8 (12.5%)	1
Dry Skin	0/8 (0%)	0	0/9 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1
Social circumstances
Rash/desquamation	2/8 (25%)	2	1/9 (11.1%)	1	1/7 (14.3%)	1	0/8 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.