Ignite Creation Date:
2024-05-05 @ 11:43 AM
Last Modification Date:
2024-10-26 @ 9:12 AM
Study NCT ID:
NCT00113984
Status:
COMPLETED
Last Update Posted:
2019-12-16
First Post:
2005-06-11
Brief Title:
Vaccine and Antibody Treatment of Prostate Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase I Trial of a PSA Based Vaccine and an Anti-CTLA-4 Antibody in Adults With Metastatic Androgen Independent Prostrate Cancer
Status:
COMPLETED
Status Verified Date:
2012-11-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will evaluate the side effects of a fixed dose of vaccine and GM-CSF with increasing doses of anti-CTLA-4 antibody in patients with advanced prostate cancer The vaccine consists of a priming vaccine called PROSTVACTRICOM made from vaccinia virus and a boosting vaccine called PROSTVAC-FTRICOM made from fowlpox virus GM-CSF is a chemical that boosts the immune system and anti-CTLA-4 antibody is a protein that may improve anti-tumor activity and the response to the vaccines DNA is inserted into the priming and boosting vaccine viruses to cause production of proteins that enhance immune activity and also to produce prostate specific antigen PSA-a protein that is normally produced by the patients tumor cells
Patients 18 years of age and older with androgen-insensitive prostate cancer that has spread beyond the original site may be eligible for this 7-month study Candidates must have disease that has worsened despite treatments with hormones and up to one chemotherapy regimen Their tumor must produce PSA and they must have no history of allergy to eggs or egg products Candidates are screened with a medical history and physical examination blood and urine tests electrocardiogram pathological confirmation of the diagnosis and presence of the PSA marker chest x-rays imaging studies to assess the extent of tumor and if clinically indicated a cardiologic evaluation
Participants receive the priming vaccination on study day 1 After 2 weeks and then again every 4 weeks while on the study they receive a boosting vaccine All vaccines are injected under the skin On the day of each vaccination and daily for the next 3 days patients receive an injection of GM-CSF to increase the number of immune cells at the vaccination site On the day of the first six boosting vaccinations they receive anti-CTLA-4 antibody as an infusion through a vein over 90 minutes
Patients are monitored for safety and treatment response with the following tests and procedures
Blood and urine tests monthly or more often if needed to monitor liver kidney and other organ function
Imaging studies to assess the tumor before starting treatment again around study days 99 and 183 and then every 3 months after that while on study
Apheresis a procedure for collecting immune cells called lymphocytes to measure the immune response to treatment Apheresis is done three times before starting the study and again around study days 99 and 183 For this procedure blood is collected through a needle in an arm vein The blood circulates through a machine that separates it into its components by spinning and the lymphocytes are extracted The rest of the blood is returned to the patient through the same needle This will only be done in participants who have the tissue marker HLA-A2 about 50 of patients
Patients whose disease responds to treatment and who do not develop severe side effects may continue treatment beyond the initial 7-month study period on vaccine alone without the antibody After treatment is completed patients are monitored for up to 15 years This includes a medical history and physical examination for 5 years following the last vaccination Information beyond 5 years is collected once a year by telephone
Patients 18 years of age and older with androgen-insensitive prostate cancer that has spread beyond the original site may be eligible for this 7-month study Candidates must have disease that has worsened despite treatments with hormones and up to one chemotherapy regimen Their tumor must produce PSA and they must have no history of allergy to eggs or egg products Candidates are screened with a medical history and physical examination blood and urine tests electrocardiogram pathological confirmation of the diagnosis and presence of the PSA marker chest x-rays imaging studies to assess the extent of tumor and if clinically indicated a cardiologic evaluation
Participants receive the priming vaccination on study day 1 After 2 weeks and then again every 4 weeks while on the study they receive a boosting vaccine All vaccines are injected under the skin On the day of each vaccination and daily for the next 3 days patients receive an injection of GM-CSF to increase the number of immune cells at the vaccination site On the day of the first six boosting vaccinations they receive anti-CTLA-4 antibody as an infusion through a vein over 90 minutes
Patients are monitored for safety and treatment response with the following tests and procedures
Blood and urine tests monthly or more often if needed to monitor liver kidney and other organ function
Imaging studies to assess the tumor before starting treatment again around study days 99 and 183 and then every 3 months after that while on study
Apheresis a procedure for collecting immune cells called lymphocytes to measure the immune response to treatment Apheresis is done three times before starting the study and again around study days 99 and 183 For this procedure blood is collected through a needle in an arm vein The blood circulates through a machine that separates it into its components by spinning and the lymphocytes are extracted The rest of the blood is returned to the patient through the same needle This will only be done in participants who have the tissue marker HLA-A2 about 50 of patients
Patients whose disease responds to treatment and who do not develop severe side effects may continue treatment beyond the initial 7-month study period on vaccine alone without the antibody After treatment is completed patients are monitored for up to 15 years This includes a medical history and physical examination for 5 years following the last vaccination Information beyond 5 years is collected once a year by telephone
Detailed Description:
Background
Adenocarcinoma of the prostate is the most common cancer diagnosis in American males and the second leading cause of cancer death
The proposed vaccine strategy represents a third-generation design that elicits a T-cell immune response to cells expressing PSA and has been shown to break tolerance to this self-antigen and cause objective response and PSA declines in patients with metastatic AIPC
This strategy also utilizes an antibody to CTLA-4 that may block the normal signals to down regulate the immune response following active vaccination
Anti CTLA-4 antibodies have been associated with autoimmune events that are generally manageable and have been associated with clinical response
Objectives
To determine the safety and tolerability of a combination of a fixed dose of vaccine and anti-CTLA4 which will be dose escalated
To evaluate immunologic response as measured by an increase in PSA specific T-cells measured by ELISPOT in HLA-A2 patients and clinical response as measured by RECIST and PSA consensus criteria
Eligibility
Must have metastatic androgen insensitive prostate cancer with no bone pain requiring narcotics and have had no more prior chemotherapy
Life expectancy greater than or equal to 6 months ECOG 0-1
Should have no autoimmune diseases no evidence of being immunocompromised no serious intercurrent medical illness no cardiac disease no prior splenectomy
No prior treatment with MDX-010 Ipilimumab
No brain metastasis history of seizures encephalitis or multiple sclerosis
No serious hypersensitivity reaction to egg products
Design
This is an open label phase I safety trial with sequential cohorts of patients all receiving a fixed dose of PSA-TRICOM vaccines and sargramostim with dose escalation of MDX-010 Ipilimumab
PROSTVAC -VTRICOM vaccinia 2 x 108 pfu subcutaneously will be administered as the initial priming vaccine on day 1 of cycle 1 only
PROSTVAC -FTRICOM fowlpox 1 x 109 pfu subcutaneously starting on day 15 followed by monthly boosting vaccination Sargramostim 100 mcg per day will be administered subcutaneously at the vaccination site on days 1-4 of each vaccine cycle prime and boost
MDX-010 Ipilimumab will be administered as per the assigned dose level as a 90-minute intravenous infusion on the same day as the monthly boosting vaccinations with PROSTVAC-FTRICOM fowlpox After 6 courses of MDX-010 patients may receive Maintenance dose of MDX-010 every 3 months until there is evidence of disease progression or toxicity for up to an additional 12 months equivalent to 4 additional MDX-010 courses
Monthly boosting vaccinations with PROSTVAC-FTRICOM fowlpox and sargramostim may then continue until patients meet off study criteria
Adenocarcinoma of the prostate is the most common cancer diagnosis in American males and the second leading cause of cancer death
The proposed vaccine strategy represents a third-generation design that elicits a T-cell immune response to cells expressing PSA and has been shown to break tolerance to this self-antigen and cause objective response and PSA declines in patients with metastatic AIPC
This strategy also utilizes an antibody to CTLA-4 that may block the normal signals to down regulate the immune response following active vaccination
Anti CTLA-4 antibodies have been associated with autoimmune events that are generally manageable and have been associated with clinical response
Objectives
To determine the safety and tolerability of a combination of a fixed dose of vaccine and anti-CTLA4 which will be dose escalated
To evaluate immunologic response as measured by an increase in PSA specific T-cells measured by ELISPOT in HLA-A2 patients and clinical response as measured by RECIST and PSA consensus criteria
Eligibility
Must have metastatic androgen insensitive prostate cancer with no bone pain requiring narcotics and have had no more prior chemotherapy
Life expectancy greater than or equal to 6 months ECOG 0-1
Should have no autoimmune diseases no evidence of being immunocompromised no serious intercurrent medical illness no cardiac disease no prior splenectomy
No prior treatment with MDX-010 Ipilimumab
No brain metastasis history of seizures encephalitis or multiple sclerosis
No serious hypersensitivity reaction to egg products
Design
This is an open label phase I safety trial with sequential cohorts of patients all receiving a fixed dose of PSA-TRICOM vaccines and sargramostim with dose escalation of MDX-010 Ipilimumab
PROSTVAC -VTRICOM vaccinia 2 x 108 pfu subcutaneously will be administered as the initial priming vaccine on day 1 of cycle 1 only
PROSTVAC -FTRICOM fowlpox 1 x 109 pfu subcutaneously starting on day 15 followed by monthly boosting vaccination Sargramostim 100 mcg per day will be administered subcutaneously at the vaccination site on days 1-4 of each vaccine cycle prime and boost
MDX-010 Ipilimumab will be administered as per the assigned dose level as a 90-minute intravenous infusion on the same day as the monthly boosting vaccinations with PROSTVAC-FTRICOM fowlpox After 6 courses of MDX-010 patients may receive Maintenance dose of MDX-010 every 3 months until there is evidence of disease progression or toxicity for up to an additional 12 months equivalent to 4 additional MDX-010 courses
Monthly boosting vaccinations with PROSTVAC-FTRICOM fowlpox and sargramostim may then continue until patients meet off study criteria
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 05-C-0167 | None | None | None |