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.

OUTLINE: This is a dose-escalation study.

Patients receive ultrasound-guided intratumoral injections of adenoviral vector-delivered interleukin-12 gene (ADV-hIL12) on day 1.

Cohorts of 3-6 patients receive escalating doses of ADV-hIL12 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at days 11, 15, 29, 43, and 57 and are then followed for survival thereafter.

PROJECTED ACCRUAL: A total of 30-36 patients will be accrued for this study.

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 immunosupppressive drugs
• No concurrent immunosuppressive drugs
• No concurrent anticoagulant therapy with heparin or warfarin