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

Max Sung

Status and phase: Terminated; Phase 1

Conditions: Metastatic Cancer; Colorectal Cancer

Treatments: Biological: adenovirus vector; Biological: interleukin-12 gene

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00072098

GCO 97-0564

MTS-GCO-971592

MTS-GCO-975642

NIH 9911-359

CDR0000335463

Details and patient eligibility

About

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.

Full 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.

Enrollment: 22 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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22 participants in 1 patient group

Experimental Group

Experimental group

Description:

Direct intratumoral injection of metastatic hepatic tumors using an adenoviral vector expressing the human recombinant interleukin-12 gene

Treatment:

Biological: adenovirus vector

Biological: interleukin-12 gene