Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Active Adult NCI MTS-GCO-975642 MTS-GCO-971592, NCT00072098

Objectives

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

Entry 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

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

Patient Characteristics:

Age

• Adult

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 16 weeks

Hematopoietic

• Granulocyte count at least 1,500/mm³
• Hemoglobin at least 9.0 g/dL
• Platelet count at least 100,000/mm³

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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Mount Sinai Medical Center

Max Sung, MD, Principal investigator		Ph: 212-241-7902 Email: max.sung@mssm.edu

U.S.A.
New York
	New York
	Mount Sinai Medical Center
		Max Sung, MD	Ph:  212-241-7902
			Email: max.sung@mssm.edu

Registry Information
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
Trial Start Date		2003-09-22
Registered in ClinicalTrials.gov		NCT00072098
Date Submitted to PDQ		2003-09-17
Information Last Verified		2007-01-18
NCI Grant/Contract Number		R21-CA81265