Ignite Creation Date:
2024-05-05 @ 11:35 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00081848
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2004-04-22
Brief Title:
Vaccine Therapy and Radiation to Liver Metastasis in Patients With CEA-Positive Solid Tumors
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Pilot Trial of a CEA-TRICOM Based Vaccine and Radiation to Liver Metastasis in Adults With CEA Positive Solid Tumors
Status:
COMPLETED
Status Verified Date:
2012-01-25
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 safety and effects of vaccine treatment plus radiation to the liver in patients with solid tumors that have spread to the liver The vaccine treatment consists of three parts 1 a priming vaccine called rV-CEA6D-TRICOM made from vaccinia virus 2 a boosting vaccine called rF-CEA6D-TRICOM made from fowlpox virus and 3 a fowlpox virus injected with DNA for GM-CSF a chemical that boosts the immune system called rF-GM-CSF Human DNA is inserted into the priming and boosting vaccine viruses to cause production of proteins that enhance immune activity and also to produce carcinoembryonic antigen CEA - a protein that is normally produced by the patients tumor cells The study also uses radiation because laboratory and animal studies show that low doses of radiation to tumors that produce CEA make the tumor more sensitive to the effects of the vaccines
Patients 18 years of age and older who have a solid tumor that has spread to the liver may be eligible for this study Candidates must have had at least one course of chemotherapy for metastatic disease and their tumor must produce CEA Candidates are screened with a medical history and physical examination blood and urine tests test of pathology slides from surgery to determine the presence of the CEA marker imaging studies to assess the extent of tumor and an electrocardiogram and cardiologic evaluation if clinically indicated
Participants receive the priming vaccination on study day 1 After 3 weeks and then again every 2 weeks for 2 months study days 21 35 49 and 63 they receive a boosting vaccine All vaccines are injected under the skin With every vaccination they also receive an injection of rF-GM-CSF to increase the number of immune cells at the vaccination site The day after each of the first four boosting vaccinations patients undergo 4 consecutive days of radiation to the tumor in the liver study days 22-25 36-39 50-53 and 64-67 Patients may continue treatment with monthly booster vaccinations without further radiation therapy as long as their cancer does not get worse and they do not develop serious treatment side effects
Patients are monitored for safety and treatment response with the following tests and procedures
Blood and urine tests and clinic visits every 2 to 4 weeks to monitor liver kidney and other organ function
Imaging studies to assess the tumor around study day 91 and every 2 months after that while on the study
Apheresis a procedure for collecting immune cells called lymphocytes - Apheresis is done before the first vaccination on study day 1 and again around study day 91 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 The collected lymphocytes are studied to measure the immune response to treatment
Liver biopsy optional - This test is done once before starting radiation treatment and again around 3 to 7 days after completing the first dose of radiation The biopsy provides information on the type of cancer the level of CEA produced by the tumor and the immune status of the tumor For this procedure the skin over the liver is numbed with an anesthetic a needle is placed in the liver tumor and a small sample of tumor is withdrawn through the needle
After treatment is completed patients are monitored for up to 15 years including yearly medical histories and physical examinations for 5 years following their last vaccination Information beyond 5 years is collected once a year by telephone
Patients 18 years of age and older who have a solid tumor that has spread to the liver may be eligible for this study Candidates must have had at least one course of chemotherapy for metastatic disease and their tumor must produce CEA Candidates are screened with a medical history and physical examination blood and urine tests test of pathology slides from surgery to determine the presence of the CEA marker imaging studies to assess the extent of tumor and an electrocardiogram and cardiologic evaluation if clinically indicated
Participants receive the priming vaccination on study day 1 After 3 weeks and then again every 2 weeks for 2 months study days 21 35 49 and 63 they receive a boosting vaccine All vaccines are injected under the skin With every vaccination they also receive an injection of rF-GM-CSF to increase the number of immune cells at the vaccination site The day after each of the first four boosting vaccinations patients undergo 4 consecutive days of radiation to the tumor in the liver study days 22-25 36-39 50-53 and 64-67 Patients may continue treatment with monthly booster vaccinations without further radiation therapy as long as their cancer does not get worse and they do not develop serious treatment side effects
Patients are monitored for safety and treatment response with the following tests and procedures
Blood and urine tests and clinic visits every 2 to 4 weeks to monitor liver kidney and other organ function
Imaging studies to assess the tumor around study day 91 and every 2 months after that while on the study
Apheresis a procedure for collecting immune cells called lymphocytes - Apheresis is done before the first vaccination on study day 1 and again around study day 91 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 The collected lymphocytes are studied to measure the immune response to treatment
Liver biopsy optional - This test is done once before starting radiation treatment and again around 3 to 7 days after completing the first dose of radiation The biopsy provides information on the type of cancer the level of CEA produced by the tumor and the immune status of the tumor For this procedure the skin over the liver is numbed with an anesthetic a needle is placed in the liver tumor and a small sample of tumor is withdrawn through the needle
After treatment is completed patients are monitored for up to 15 years including yearly medical histories and physical examinations for 5 years following their last vaccination Information beyond 5 years is collected once a year by telephone
Detailed Description:
Background
A phase I clinical trial with this same vaccine alone was associated with stable disease at least 4 months in 40 of patients and 1 pathologic complete response
Radiation therapy upregulates Fas on tumor cells allowing for easier killing by antigen specific activated T cells Dominant negative fas transfected tumor cells demonstrated the anti-tumor effects were fas mediated
Radiation has been shown to up-regulate ICAM tumor associated antigens and MHC class I on human tumor cell lines in vitro
TRICOM vaccines act synergistically with radiation in tumor treatment models
Radiation therapy at the doses we propose appears to have a favorable safety profile
Clinical trials using PSA vaccine shows that local radiation of tumor does not inhibit vaccine efficacy
Objectives
1 Safety of the combination of a CEA based vaccine and radiation
2 clinical response
2 Immunohistochemistry - FAS MHC p53 and CEA on tumor before and after radiation therapy
2 Immunological response ELISPOT assay
Eligibility
Solid Tumors expressing CEA positive cancer with radiographically visible metastatic liver lesions
Completed at least one chemotherapy regimen for metastatic disease
Life expectancy greater than or equal to 6 months
Adequate organ function
ECOG 0-1
No autoimmunity
No serum positivity for HIV Hepatitis B or C viruses
Design
Single cohort pilot study of vaccine and radiation therapy to liver lesions in 10 evaluable patients All vaccines and radiation are given at the NIH Clinical Center
Vaccine
rV-CEA6DTRICOM 12 x 108 PFU subcutaneously sc day 1
rF-CEA6DTRICOM 4 x 108 PFU sc days 21 35 49 and 63
All vaccinations will be given with rF-GM-CSF 1 x 107 pfu sc
-Radiation 2 Gyd for 4 days after each dose of rF-CEA6DTRICOM on days 22-25 36-39 50-53 and 64-67 total planned radiation dose per patient is 32 Gy
A phase I clinical trial with this same vaccine alone was associated with stable disease at least 4 months in 40 of patients and 1 pathologic complete response
Radiation therapy upregulates Fas on tumor cells allowing for easier killing by antigen specific activated T cells Dominant negative fas transfected tumor cells demonstrated the anti-tumor effects were fas mediated
Radiation has been shown to up-regulate ICAM tumor associated antigens and MHC class I on human tumor cell lines in vitro
TRICOM vaccines act synergistically with radiation in tumor treatment models
Radiation therapy at the doses we propose appears to have a favorable safety profile
Clinical trials using PSA vaccine shows that local radiation of tumor does not inhibit vaccine efficacy
Objectives
1 Safety of the combination of a CEA based vaccine and radiation
2 clinical response
2 Immunohistochemistry - FAS MHC p53 and CEA on tumor before and after radiation therapy
2 Immunological response ELISPOT assay
Eligibility
Solid Tumors expressing CEA positive cancer with radiographically visible metastatic liver lesions
Completed at least one chemotherapy regimen for metastatic disease
Life expectancy greater than or equal to 6 months
Adequate organ function
ECOG 0-1
No autoimmunity
No serum positivity for HIV Hepatitis B or C viruses
Design
Single cohort pilot study of vaccine and radiation therapy to liver lesions in 10 evaluable patients All vaccines and radiation are given at the NIH Clinical Center
Vaccine
rV-CEA6DTRICOM 12 x 108 PFU subcutaneously sc day 1
rF-CEA6DTRICOM 4 x 108 PFU sc days 21 35 49 and 63
All vaccinations will be given with rF-GM-CSF 1 x 107 pfu sc
-Radiation 2 Gyd for 4 days after each dose of rF-CEA6DTRICOM on days 22-25 36-39 50-53 and 64-67 total planned radiation dose per patient is 32 Gy
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 |
|---|---|---|---|
| 04-C-0167 | None | None | None |