Ignite Creation Date:
2024-05-05 @ 11:25 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00035919
Status:
WITHDRAWN
Last Update Posted:
2014-05-22
First Post:
2002-05-06
Brief Title:
Safety and Efficacy of Targeted Gene Transfer in Colorectal Cancer Metastatic to Liver
Sponsor:
University of Southern California
Organization:
University of Southern California
Study Overview
Official Title:
Tumor Site Specific Phase I Evaluation of Safety of Hepatic Arterial Infusion of a Matrix-Targeted Retroviral Vector Bearing a Dominant Negative Cyclin G1 Construct as Intervention for Colorectal Carcinoma Metastatic to Liver
Status:
WITHDRAWN
Status Verified Date:
2014-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Never received final IRB approval for amendments so never opened officially
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a Phase I safety study of a gene transfer drug for colorectal cancer that has spread to the liver The main purpose of this study is to determine if it is safe to give this new intervention to persons with cancer but we will also look for indications that the drug is effective Although the findings in animals that have cancer are encouraging this is the first time humans will receive this experimental gene transfer drug A gene called cyclin G1 has been shown to play a very important part in cancer growth In animal experiments a genetically modified virus or vectorcarrying a modified cyclin G1 gene caused the cancerous tumors to grow much slower or even die In this safety study the drug will be injected through the liver artery to get it near the cancer that has spread to the liver The way the gene gets into the cancer cells is by using a targeted vector that concentrates in the area of the cancer to improve the delivery of the killing gene into cancer cells The vector we are using is a virus that has been changed so that the infectious genes have been removed and instead carries the modified cyclin G1 gene
Detailed Description:
Objectives
1 To evaluate the safetytoxicity of hepatic arterial administration of a matrix-targeted retroviral vector bearing a dnG1 construct Mx-dnG1
2 To evaluate the pharmacodynamics of hepatic arterial infusion of the Mx-dnG1 retroviral vector administered as hepatic arterial infusion
3 To obtain preliminary data on molecular markers of tumor response
4 To identify an anti-tumor response to hepatic artery administered Mx-dnG1 retroviral vector
Population Male and female patients 18 years old with metastatic colorectal carcinoma
Sample Size Nine to fifteen patients 3 to 6 patients treated at each of three dose levels
Dosage Treatment Hepatic arterial infusion of the Mx-dnG1 retroviral vector once a day on days 1-5
Three patients will receive the Mx-dnG1 retroviral vector at Dose Level I If 1 of 3 patients at Dose Level I develops a grade 3 or 4 adverse event CTC Version 20 which appears to be related or possibly related to the Mx-dnG1 retroviral vector then 3 additional patients will be enrolled at the same dose level If at least 2 of the first 3 or 3 of 6 patients at Dose Level I develop a grade 3 to 4 adverse event which appears to be related or possibly related to the Mx-dnG1 retroviral vector accrual into the study will be held until the data are discussed with the Food and Drug Administration FDA and a decision is made whether to continue or terminate study enrollment
If none of the first 3 or no more than 1 of the first 6 patients that have received vector at Dose Level I develop a grade 3 or 4 adverse event which appears to be related or possibly related to the dnG1 retroviral vector the dose of the vector will be escalated as follows
Dose LeveL---No of Patients---Vector Dose---Maximum Volume
I----------------3------------3 X 10e9 cfu-------500 ml
II---------------3------------6 X 10e9 cfu-------500 ml
III--------------3------------1 X 10e10 cfu------500 ml
The intervention plan will be identical to the one described above for Dose Level I The Maximum Tolerated Dose MTD will be defined as one dose level below the level at which dose limiting toxicity is observed
Primary Endpoint Clinical toxicity DLT and MTD as defined by patient performance status toxicity assessment score hematologic liver and coagulation profile
Secondary Endpoint Obtain preliminary data on molecular markers of tumor response To assess decrease in tumor size as detected by abdominal CT Scan at 3 and 6 weeks after treatment Evaluate the pharmacodynamics of hepatic arterial infusion of the Mx-dnG1 retroviral vector administered as hepatic arterial infusion
1 To evaluate the safetytoxicity of hepatic arterial administration of a matrix-targeted retroviral vector bearing a dnG1 construct Mx-dnG1
2 To evaluate the pharmacodynamics of hepatic arterial infusion of the Mx-dnG1 retroviral vector administered as hepatic arterial infusion
3 To obtain preliminary data on molecular markers of tumor response
4 To identify an anti-tumor response to hepatic artery administered Mx-dnG1 retroviral vector
Population Male and female patients 18 years old with metastatic colorectal carcinoma
Sample Size Nine to fifteen patients 3 to 6 patients treated at each of three dose levels
Dosage Treatment Hepatic arterial infusion of the Mx-dnG1 retroviral vector once a day on days 1-5
Three patients will receive the Mx-dnG1 retroviral vector at Dose Level I If 1 of 3 patients at Dose Level I develops a grade 3 or 4 adverse event CTC Version 20 which appears to be related or possibly related to the Mx-dnG1 retroviral vector then 3 additional patients will be enrolled at the same dose level If at least 2 of the first 3 or 3 of 6 patients at Dose Level I develop a grade 3 to 4 adverse event which appears to be related or possibly related to the Mx-dnG1 retroviral vector accrual into the study will be held until the data are discussed with the Food and Drug Administration FDA and a decision is made whether to continue or terminate study enrollment
If none of the first 3 or no more than 1 of the first 6 patients that have received vector at Dose Level I develop a grade 3 or 4 adverse event which appears to be related or possibly related to the dnG1 retroviral vector the dose of the vector will be escalated as follows
Dose LeveL---No of Patients---Vector Dose---Maximum Volume
I----------------3------------3 X 10e9 cfu-------500 ml
II---------------3------------6 X 10e9 cfu-------500 ml
III--------------3------------1 X 10e10 cfu------500 ml
The intervention plan will be identical to the one described above for Dose Level I The Maximum Tolerated Dose MTD will be defined as one dose level below the level at which dose limiting toxicity is observed
Primary Endpoint Clinical toxicity DLT and MTD as defined by patient performance status toxicity assessment score hematologic liver and coagulation profile
Secondary Endpoint Obtain preliminary data on molecular markers of tumor response To assess decrease in tumor size as detected by abdominal CT Scan at 3 and 6 weeks after treatment Evaluate the pharmacodynamics of hepatic arterial infusion of the Mx-dnG1 retroviral vector administered as hepatic arterial infusion
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