Interleukin-12 Gene in Treating Patients With Liver Metastases Secondary to Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Inserting the interleukin-12 gene into a person's cancer cells may make the body build an immune response to kill tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of interleukin-12 gene when injected into the tumors of patients with liver metastases secondary to colorectal cancer.

Detailed Description
-----------------
OBJECTIVES: Determine the toxicity and maximum tolerated dose of intratumoral adenoviral vector-delivered interleukin-12 gene in patients with liver metastases secondary to colorectal cancer . Determine the tumor response in patients treated with this regimen. Determine the immune response in patients treated with this regimen.

Official Title
-----------------
Phase I Trial Of Adenoviral Vector Delivery Of The Human Interleukin-12 cDNA By Intratumoral Injection In Patients With Metastatic Colorectal Cancer To The Liver

Conditions
-----------------
Colorectal Cancer, Metastatic Cancer

Intervention / Treatment
-----------------
* Biological: adenovirus vector
* Biological: interleukin-12 gene


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed* colorectal adenocarcinoma metastatic to the liver Solitary or multiple metastatic tumors in the liver Metastatic involvement of the liver no greater than 40% of estimated liver volume NOTE: *Must be from the hepatic tumor designated for study injection Metastatic liver tumors must be bidimensionally measurable by CT scan or MRI At least 1 metastatic liver tumor measuring at least 2.0 cm must be visualized by ultrasound (US) and accessible for US-guided percutaneous injection Extrahepatic metastases allowed No prior or current ascites Ineligible for hepatic resection PATIENT CHARACTERISTICS: Age Adult Performance status Karnofsky 70-100% Life expectancy At least 16 weeks Hematopoietic Granulocyte count at least 1,500/mm^3 Hemoglobin at least 9.0 g/dL Platelet count at least 100,000/mm^3 Hepatic No clinical evidence of other severe liver disease (e.g., portosystemic encephalopathy) PT no greater than 14 seconds Bilirubin no greater than 2.0 times upper limit of normal (ULN) Transaminases no greater than 2.5 times ULN Renal Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 45 mL/min Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective nonhormonal contraception during and for at least 2 months after study participation HIV negative No active infection No other concurrent serious medical illness No other malignancy within the past 5 years except inactive nonmelanoma skin cancer, carcinoma in situ of the cervix, or grade 1 papillary bladder cancer Oriented and rational Weight at least 30 kg PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) Endocrine therapy At least 2 months since prior corticosteroids Radiotherapy Not specified Surgery Not specified Other At least 2 months since prior systemic immunosuppressive drugs No concurrent immunosuppressive drugs No concurrent anticoagulant therapy with heparin or warfarin

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>Direct intratumoral injection of metastatic hepatic tumors using an adenoviral vector expressing the human recombinant interleukin-12 gene | Biological: adenovirus vector<br> <br> Biological: interleukin-12 gene<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety measure | adverse event reporting | up to day 57 | 
| toxicity grading | toxicity will assessed from grades 0 to 4 as per common toxicity criteria | up to day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tumor response compared at four weeks to baseline | tumor masses enumerated and measured pre-treatment and 4 weeks after treatment and changes in the tumor calculated. | baseline and four weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IV colon cancer, stage IV rectal cancer, liver metastases, recurrent rectal cancer, recurrent colon cancer