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

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

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer; Metastatic Cancer
• Intervention / Treatment: Biological: interleukin-12 gene; Biological: adenovirus vector

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Max Sung
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Max W. Sung, MD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: November 4, 2003
• First Submitted That Met QC Criteria: November 5, 2003
• First Posted (Estimate): November 6, 2003

Study Record Updates

• Last Update Posted (Estimate): January 11, 2017
• Last Update Submitted That Met QC Criteria: January 10, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer; liver metastases
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Adjuvants, Immunologic; Interleukin-12
• Other Study ID Numbers: GCO 97-0564; MTS-GCO-975642; MTS-GCO-971592; CDR0000335463; NIH 9911-359