Ignite Creation Date:
2024-05-05 @ 5:27 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00450463
Status:
COMPLETED
Last Update Posted:
2018-11-29
First Post:
2007-03-20
Brief Title:
Vaccine Therapy With PROSTVACTRICOM and Flutamide Versus Flutamide Alone to Treat Prostate Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Randomized Phase II Trial Combining Vaccine Therapy With PROSTVACTRICOM and Flutamide vs Flutamide Alone in Men With Androgen Insensitive Non-Metastatic D05 Prostate Cancer
Status:
COMPLETED
Status Verified Date:
2018-11
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:
Background
Flutamide is an approved drug for prostate cancer that blocks the effects of testosterone on prostate cancer cells and may slow the progression of the disease
The vaccine in this study consists of a priming vaccine called PROSTVAC rilimogene galvacirepvecrilimogene glafolivec -VTRICOM triad of costimulatory molecules made from vaccinia virus and a boosting vaccine called PROSTVAC-FTRICOM made from fowlpox virus DNA Deoxyribonuceic acid 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
GM-CSF granulocyte macrophage colony stimulating factor given along with the vaccine is a chemical that boosts the immune system It is used in this study to try to increase the usefulness of the vaccine by increasing the number of immune cells at the vaccination site
Objectives
-To determine if treatment with a prostate cancer vaccine plus flutamide is more effective than flutamide alone in delaying disease progression in patients with prostate cancer
Eligibility
Patients 18 years of age and older with androgen-insensitive prostate cancer that has not spread beyond the prostate gland
Patients with a rising PSA prostatic specific antigen who have already been treated with anti-iandrogen therapy either bicalutamide or nilutamide
Design
There are two treatment groups in this study Group A receives only flutamide group B receive flutamide plus vaccine
Patients in both groups receive flutamide by mouth three times a day
Patients in group B receive PROSTVAC-VTRICOM on day 1 and PROSTVAC-FTRICOM on day 29 and again every 4 weeks All vaccines are given as injections under the skin
Patients have blood tests for PSA levels every month and scans every 3 months until the disease worsens
After 3 months of therapy patients receiving in group A flutamide alone may cross over to receive vaccine if they develop a rising PSA and scans show no sign of disease spread Patients in group B flutamide plus vaccine stop flutamide and may continue vaccine therapy At this point patients may continue to receive treatment until the disease progresses or PSA levels rise
Flutamide is an approved drug for prostate cancer that blocks the effects of testosterone on prostate cancer cells and may slow the progression of the disease
The vaccine in this study consists of a priming vaccine called PROSTVAC rilimogene galvacirepvecrilimogene glafolivec -VTRICOM triad of costimulatory molecules made from vaccinia virus and a boosting vaccine called PROSTVAC-FTRICOM made from fowlpox virus DNA Deoxyribonuceic acid 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
GM-CSF granulocyte macrophage colony stimulating factor given along with the vaccine is a chemical that boosts the immune system It is used in this study to try to increase the usefulness of the vaccine by increasing the number of immune cells at the vaccination site
Objectives
-To determine if treatment with a prostate cancer vaccine plus flutamide is more effective than flutamide alone in delaying disease progression in patients with prostate cancer
Eligibility
Patients 18 years of age and older with androgen-insensitive prostate cancer that has not spread beyond the prostate gland
Patients with a rising PSA prostatic specific antigen who have already been treated with anti-iandrogen therapy either bicalutamide or nilutamide
Design
There are two treatment groups in this study Group A receives only flutamide group B receive flutamide plus vaccine
Patients in both groups receive flutamide by mouth three times a day
Patients in group B receive PROSTVAC-VTRICOM on day 1 and PROSTVAC-FTRICOM on day 29 and again every 4 weeks All vaccines are given as injections under the skin
Patients have blood tests for PSA levels every month and scans every 3 months until the disease worsens
After 3 months of therapy patients receiving in group A flutamide alone may cross over to receive vaccine if they develop a rising PSA and scans show no sign of disease spread Patients in group B flutamide plus vaccine stop flutamide and may continue vaccine therapy At this point patients may continue to receive treatment until the disease progresses or PSA levels rise
Detailed Description:
Background
There is no standard of care for prostate cancer patients progressing on hormone therapy with a rising serum PSA prostatic specific antigen level without evidence of metastatic disease
We have completed a phase II trial in which men with this stage of disease were randomized to receive a pox vector PSA vaccine vs the antiandrogen nilutamide
The median time to treatment failure on nilutamide was 76 months
12 patients on the vaccine arm had nilutamide added at the time of PSA progression
The median time for treatment failure after the addition of nilutamide was 139 months for a total of 259 months from initiation of vaccine therapy
This suggests that the combination of hormone therapy with vaccine therapy may lead to an improved clinical benefit compared to hormone therapy alone
Due to the increased toxicity of nilutamide compared to other antiandrogens and the patients prior exposure to bicalutamide therapy we plan to use flutamide as a second line hormonal manipulation in the below study
Objectives Primary
-To determine if use of a combination of vaccine plus flutamide may be associated with a trend toward improvement in time to treatment failure compared to flutamide alone
Eligibility
Must have non metastatic androgen insensitive prostate cancer with a rising PSA with castrate levels of testosterone and no evidence of metastatic disease on CT computed tomography scan or bone scan
Hgb hemoglobin greater than or equal to 9 gdL
Lymphocyte count greater than or equal to 500mm3
Hepatic function Bilirubin less than or equal to 15 mgdL OR patients with Gilberts syndrome a total bilirubin less than or equal to 30 mgdL AST aspartate aminotransferase and ALT alanine aminotransferase less than 25 times upper limit of normal
Design
-Flutamide will be administered at a dose of 250 mg PO by mouth tid three times a day every day in both arms A and B
rV-PSATRICOM will be administered sc subcutaneous on day 1 in Arm B
rF-PSATRICOM will be administered sc on day 29 every 4 weeks in Arm B
For patients with declining PSA no restaging will be done unless they develop symptoms consistent with metastatic disease
For patients with rising PSA once 2 consecutive PSA rises are seen a CT will be done at their next scheduled visit They will then be re-staged CT and bone scans at 3 month intervals as long as PSA continues to rise
After 3 months of therapy patients receiving the flutamide alone arm A may cross over to receive vaccine if they develop a rising PSA and scans are without metastatic disease The vaccine may commence 4 weeks after flutamide is stopped if the PSA continues to rise If there is an antiandrogen withdrawal response a decline in PSA 28 days after the discontinuation of flutamide PSA serum levels will be checked every 28 days and vaccine may commence when the serum PSA levels begin to rise if scans are negative for metastatsis Patients on arm B will have flutamide discontinued and may continue vaccine therapy At this point patients may continue to receive treatment on study until the development of disease on scans or a second occurrence of clinical progression
Patients who have been on study for 2 years or more with stable disease and who are not getting vaccine clinic visits may be scheduled every 8 weeks Patients receiving monthly vaccine will continue to have monthly visits
For patients who have stable disease and attend clinic every 8 weeks once 2 consecutive PSA rises are seen a CT and bone scan will be done at their next visit in 4 weeks They will then be restaged CT and bone scans at 3 month intervals as long as PSA continues to rise
There is no standard of care for prostate cancer patients progressing on hormone therapy with a rising serum PSA prostatic specific antigen level without evidence of metastatic disease
We have completed a phase II trial in which men with this stage of disease were randomized to receive a pox vector PSA vaccine vs the antiandrogen nilutamide
The median time to treatment failure on nilutamide was 76 months
12 patients on the vaccine arm had nilutamide added at the time of PSA progression
The median time for treatment failure after the addition of nilutamide was 139 months for a total of 259 months from initiation of vaccine therapy
This suggests that the combination of hormone therapy with vaccine therapy may lead to an improved clinical benefit compared to hormone therapy alone
Due to the increased toxicity of nilutamide compared to other antiandrogens and the patients prior exposure to bicalutamide therapy we plan to use flutamide as a second line hormonal manipulation in the below study
Objectives Primary
-To determine if use of a combination of vaccine plus flutamide may be associated with a trend toward improvement in time to treatment failure compared to flutamide alone
Eligibility
Must have non metastatic androgen insensitive prostate cancer with a rising PSA with castrate levels of testosterone and no evidence of metastatic disease on CT computed tomography scan or bone scan
Hgb hemoglobin greater than or equal to 9 gdL
Lymphocyte count greater than or equal to 500mm3
Hepatic function Bilirubin less than or equal to 15 mgdL OR patients with Gilberts syndrome a total bilirubin less than or equal to 30 mgdL AST aspartate aminotransferase and ALT alanine aminotransferase less than 25 times upper limit of normal
Design
-Flutamide will be administered at a dose of 250 mg PO by mouth tid three times a day every day in both arms A and B
rV-PSATRICOM will be administered sc subcutaneous on day 1 in Arm B
rF-PSATRICOM will be administered sc on day 29 every 4 weeks in Arm B
For patients with declining PSA no restaging will be done unless they develop symptoms consistent with metastatic disease
For patients with rising PSA once 2 consecutive PSA rises are seen a CT will be done at their next scheduled visit They will then be re-staged CT and bone scans at 3 month intervals as long as PSA continues to rise
After 3 months of therapy patients receiving the flutamide alone arm A may cross over to receive vaccine if they develop a rising PSA and scans are without metastatic disease The vaccine may commence 4 weeks after flutamide is stopped if the PSA continues to rise If there is an antiandrogen withdrawal response a decline in PSA 28 days after the discontinuation of flutamide PSA serum levels will be checked every 28 days and vaccine may commence when the serum PSA levels begin to rise if scans are negative for metastatsis Patients on arm B will have flutamide discontinued and may continue vaccine therapy At this point patients may continue to receive treatment on study until the development of disease on scans or a second occurrence of clinical progression
Patients who have been on study for 2 years or more with stable disease and who are not getting vaccine clinic visits may be scheduled every 8 weeks Patients receiving monthly vaccine will continue to have monthly visits
For patients who have stable disease and attend clinic every 8 weeks once 2 consecutive PSA rises are seen a CT and bone scan will be done at their next visit in 4 weeks They will then be restaged CT and bone scans at 3 month intervals as long as PSA continues to rise
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
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 |
|---|---|---|---|
| 07-C-0107 | None | None | None |