Ignite Creation Date:
2024-05-05 @ 11:35 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00088413
Status:
COMPLETED
Last Update Posted:
2019-04-16
First Post:
2004-07-23
Brief Title:
PANVAC-V and PANVAC-F Vaccines Plus Sargramostim to Treat Advanced Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
An Open Label Pilot Study to Evaluate the Safety and Tolerability of PANVAC-V Vaccinia and PANVAC-F Fowlpox in Combination With Sargramostim in Adults With Metastatic Carcinoma
Status:
COMPLETED
Status Verified Date:
2019-04
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
Many cancers produce two proteins carcinoembryonic antigen CEA and mucin-1 MUC-1
The PANVAC-V PANVAC vaccinia priming vaccine and PANVAC-F PANVAC fowlpox boosting vaccine contain human genes that cause production of CEA and MUC-1 which can be used as a target for the immune system to attack the cancer The vaccines also contain genes that cause production of other proteins that enhance immune activity
Sargramostim is a protein that boosts the immune system
Objectives
To evaluate the safety and effectiveness of PANVAC-V and PANVAC-F in patients with advanced cancer
To document the immune response to the vaccines and any anti-tumor responses that may occur
Eligibility Patients 18 years of age and older with advanced cancer whose tumors produce CEA or MUC-1 protein
Design
This trial has three cohorts the first cohort includes 10 patients with advanced colorectal cancer and 10 to 15 patients with any advanced non-colorectal cancer that produces either EA or mitochondrial Ca2 uniporter 1 MCU-1 the second cohort includes 12 patients with advanced breast cancer and the third cohort includes 14 patients with advanced ovarian cancer
All patients receive PANVAC-V on study day 1 followed by PANVAC-F on days 15 29 and 43 then every 28 days for up to 12 vaccines followed by every 3 months until disease progression or toxicity The vaccines are given by injection under the skin Sargramostim is injected at the vaccination site on the day of each vaccination and for the next 3 days following vaccination
Patients whose scans show that their disease has progressed but who are otherwise clinically stable may revert back to monthly injections
Patients undergo apheresis to collect white blood cells lymphocytes on day 1 and day 71 of the study to measure the immune response to the treatment Blood is collected through a needle placed in one arm and directed through a cell separator machine where the lymphocytes are extracted The rest of the blood components are returned to the patient through the same needle
Patients are monitored with frequent blood tests and periodic imaging tests scans to monitor for safety and the response to treatment
Many cancers produce two proteins carcinoembryonic antigen CEA and mucin-1 MUC-1
The PANVAC-V PANVAC vaccinia priming vaccine and PANVAC-F PANVAC fowlpox boosting vaccine contain human genes that cause production of CEA and MUC-1 which can be used as a target for the immune system to attack the cancer The vaccines also contain genes that cause production of other proteins that enhance immune activity
Sargramostim is a protein that boosts the immune system
Objectives
To evaluate the safety and effectiveness of PANVAC-V and PANVAC-F in patients with advanced cancer
To document the immune response to the vaccines and any anti-tumor responses that may occur
Eligibility Patients 18 years of age and older with advanced cancer whose tumors produce CEA or MUC-1 protein
Design
This trial has three cohorts the first cohort includes 10 patients with advanced colorectal cancer and 10 to 15 patients with any advanced non-colorectal cancer that produces either EA or mitochondrial Ca2 uniporter 1 MCU-1 the second cohort includes 12 patients with advanced breast cancer and the third cohort includes 14 patients with advanced ovarian cancer
All patients receive PANVAC-V on study day 1 followed by PANVAC-F on days 15 29 and 43 then every 28 days for up to 12 vaccines followed by every 3 months until disease progression or toxicity The vaccines are given by injection under the skin Sargramostim is injected at the vaccination site on the day of each vaccination and for the next 3 days following vaccination
Patients whose scans show that their disease has progressed but who are otherwise clinically stable may revert back to monthly injections
Patients undergo apheresis to collect white blood cells lymphocytes on day 1 and day 71 of the study to measure the immune response to the treatment Blood is collected through a needle placed in one arm and directed through a cell separator machine where the lymphocytes are extracted The rest of the blood components are returned to the patient through the same needle
Patients are monitored with frequent blood tests and periodic imaging tests scans to monitor for safety and the response to treatment
Detailed Description:
Background
Carcinoembryonic antigen CEA and mucin-1 MUC-1 are overexpressed in multiple adenocarcinomas
Pox viral vectors can induce a strong immune response to CEA and MUC-1
The use of agonist epitopes within the tumor associated antigen TAA can induce a better immune response than native peptides and have been associated with clinical responses
Heterologous prime and boost regimens are superior in terms of generalizing immune responses and this may translate into improved clinical responses
The use of granulocyte-macrophage colony-stimulating factor GM-CSF does not add significant toxicity and in pre-clinical models is essential for induction for optimal immune responses
It is possible by using vectors directed against TAA that there may be additive or synergistic immune responses and this may be important in overcoming antigenic escape variance
Evidence of clinical benefit has been noted in some patients treated with this vaccine
Objectives
For colorectal cancer and non-colorectal cancer Cohort To evaluate the safety and tolerability of the vaccine
For the Ovarian Cancer and Breast Cancer Cohorts To evaluate clinical response to the vaccine
Eligibility
In the first cohort colorectal and non-colorectal cancer histologically confirmed adenocarcinoma that is CEA or MUC-1 positive described as metastatic disease measurable or evaluable or metastatic disease documented by biopsy but not evaluable by imaging eg small volume peritoneal disease
For the ovarian and breast cancer cohorts patients must have evaluable disease
Normal organ function Eastern Cooperative Oncology Group ECOG 0-1
Design
This is a non-randomized three cohort pilot trial of pox viral vaccines that contain the transgenes for CEA and MUC-1 both with modified human leukocyte antigen A2 HLA-A2 agonist epitopes as well as 3 human T-cell costimulatory molecules B7-1 ICAM-1 CD54 and LFA-3 CD58 PANVACTM-V vaccinia and PANVACTM-F fowlpox in patients with metastatic carcinoma that express CEA or MUC-1 antigen
The first cohort will enroll 10 patients with metastatic colorectal adenocarcinoma and 10-15 patients with any metastatic non-colorectal carcinoma that expresses either CEA or MUC-1
The second cohort will enroll 12 patients with metastatic breast carcinoma and 14 patients with metastatic ovarian carcinoma
All patients will receive the same vaccines on the same schedule PANVACTM-V vaccinia subcutaneously sc scheduled on day 1 followed by PANVACTM-F fowlpox sc scheduled on days 15 29 and 43 then every 28 days for up to 12 vaccines followed by every 3 months until disease progression or toxicity
Sargramostim 100 micro g will be given at the site of the vaccination PANVAC-V and PANVAC-F on each vaccination day and for three consecutive days thereafter
Patients who have radiographic evidence of progressive disease but who are otherwise clinically stable may revert back to monthly vaccinations
Carcinoembryonic antigen CEA and mucin-1 MUC-1 are overexpressed in multiple adenocarcinomas
Pox viral vectors can induce a strong immune response to CEA and MUC-1
The use of agonist epitopes within the tumor associated antigen TAA can induce a better immune response than native peptides and have been associated with clinical responses
Heterologous prime and boost regimens are superior in terms of generalizing immune responses and this may translate into improved clinical responses
The use of granulocyte-macrophage colony-stimulating factor GM-CSF does not add significant toxicity and in pre-clinical models is essential for induction for optimal immune responses
It is possible by using vectors directed against TAA that there may be additive or synergistic immune responses and this may be important in overcoming antigenic escape variance
Evidence of clinical benefit has been noted in some patients treated with this vaccine
Objectives
For colorectal cancer and non-colorectal cancer Cohort To evaluate the safety and tolerability of the vaccine
For the Ovarian Cancer and Breast Cancer Cohorts To evaluate clinical response to the vaccine
Eligibility
In the first cohort colorectal and non-colorectal cancer histologically confirmed adenocarcinoma that is CEA or MUC-1 positive described as metastatic disease measurable or evaluable or metastatic disease documented by biopsy but not evaluable by imaging eg small volume peritoneal disease
For the ovarian and breast cancer cohorts patients must have evaluable disease
Normal organ function Eastern Cooperative Oncology Group ECOG 0-1
Design
This is a non-randomized three cohort pilot trial of pox viral vaccines that contain the transgenes for CEA and MUC-1 both with modified human leukocyte antigen A2 HLA-A2 agonist epitopes as well as 3 human T-cell costimulatory molecules B7-1 ICAM-1 CD54 and LFA-3 CD58 PANVACTM-V vaccinia and PANVACTM-F fowlpox in patients with metastatic carcinoma that express CEA or MUC-1 antigen
The first cohort will enroll 10 patients with metastatic colorectal adenocarcinoma and 10-15 patients with any metastatic non-colorectal carcinoma that expresses either CEA or MUC-1
The second cohort will enroll 12 patients with metastatic breast carcinoma and 14 patients with metastatic ovarian carcinoma
All patients will receive the same vaccines on the same schedule PANVACTM-V vaccinia subcutaneously sc scheduled on day 1 followed by PANVACTM-F fowlpox sc scheduled on days 15 29 and 43 then every 28 days for up to 12 vaccines followed by every 3 months until disease progression or toxicity
Sargramostim 100 micro g will be given at the site of the vaccination PANVAC-V and PANVAC-F on each vaccination day and for three consecutive days thereafter
Patients who have radiographic evidence of progressive disease but who are otherwise clinically stable may revert back to monthly vaccinations
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 |
|---|---|---|---|
| 04-C-0246 | None | None | None |