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
1. To evaluate the safety/toxicity 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
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
Dosage Treatment: Hepatic arterial infusion of the Mx-dnG1 retroviral vector once a day on
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 2.0) 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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
dose-limiting toxicity and maximum tolerated dose
United States: Food and Drug Administration
|USC Norris Comprehensive Cancer Center||Los Angeles, California 90089|
|USC General Clinical Research Center||Los Angeles, California 90089|