Interferon-Beta Gene Transfer (Ad.hIFN-β) as Treatment for Refractory Colorectal Carcinoma With Liver Metastases

A Phase I/II Study of Interferon-Beta Gene Transfer (Ad.hIFN-β) in the Treatment of Refractory Colorectal Carcinoma With Liver Metastases

This study will be conducted in subjects with refractory colorectal carcinoma with unresectable liver metastases. The purposes of the study are:

• to evaluate the safety and any harmful effects of an intravenous injection of Ad.hIFN-β;
• help determine whether the virus carrying the interferon-beta gene will enter the bloodstream and liver tumor cells and cause the cancer cells to die.

Study Overview

• Status: Completed
• Conditions: Colorectal Carcinoma; Metastases
• Intervention / Treatment: Drug: Ad.hIFN-β (BG00001, IDEC-201)

Detailed Description

This trial is a clinical research study of Ad.hIFN-β, an investigational, replication-defective, recombinant adenovirus containing the human interferon beta gene, for people that have refractory colorectal carcinoma with liver metastases. Scientists have been exploring a variety of approaches to develop medications to treat patients with refractory colorectal carcinoma with liver metastases; a disease for which current treatment provides only limited relief, so there is a need for new medications.

• Study Type: Interventional
• Enrollment: 44
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • University of California San Diego
  • Texas
    • Dallas, Texas, United States, 75201
      • Mary Crowley Medical Research Center

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

Inclusion Criteria:

• Subjects with histologically confirmed hepatic metastases from primary colorectal carcinoma.
• Not amenable to complete surgical resection for attempted cure as determined by the Principal Investigator (PI).
• Tumor progression after prior therapy for colorectal carcinoma, including fluoropyrimidine (5 FU or capecitabine), irinotecan, oxaliplatin, or cetuximab.
• One or more metastatic hepatic tumors that is measurable on CT scan. In addition, subjects may have nonhepatic metastatic tumors.
• ECOG performance status of ≤ 1.
• Age ≥ 18 years.
• Signed, written IRB-approved informed consent.
• Men and women of reproductive potential must be willing to follow accepted birth control methods during treatment and for 3 months after completion of treatment.

• Acceptable liver function:

  • Bilirubin ≤ 1.5 x upper limit of normal;
  • AST, ALT ≤ 2.0 x upper limit of normal;
  • Albumin ≤ 3.0 g/dL.

• Acceptable hematologic status:

  • Granulocyte ≥ 1000 cells/mm3;
  • Platelet count ≥ 150,000 plts/mm3;
  • Hemoglobin > 9 g/dL.
• Acceptable coagulation status: INR within normal limits.
• Acceptable kidney function: Serum creatinine within normal limits.

Exclusion Criteria:

• New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months prior to Day 1, unstable arrhythmia, or evidence of ischemia on ECG within 14 days prior to Day 1.
• Seizure disorders requiring anticonvulsant therapy.
• Severe chronic obstructive pulmonary disease with hypoxemia.
• Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1.
• Active uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
• Pregnant or nursing women.
• Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 1 month prior to study entry.
• Unwillingness or inability to comply with procedures required in this protocol.
• Known infection with HIV, hepatitis B, or hepatitis C.
• Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor.
• Clinically significant bleeding event within the last 3 months, unrelated to trauma.
• More than 50% of liver replaced by tumor (estimated by the PI from CT scan within 14 days of Day 1).
• Previous treatment with Ad.hIFN-β.
• Any prior treatment with a gene delivery vector or an adenovirus therapeutic agent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
- Evaluate the safety of a single IV administration of Ad.hIFN-β.

Secondary Outcome Measures

Outcome Measure
Evaluate the MTD or maximum feasible dose (MFD) of Ad.hIFN-β.
Evaluate IFN-β and Ad.hIFN-β vector serum concentrations.
Evaluate immunogenicity of Ad.hIFN-β by measuring human anti adenovirus and human anti-IFN-β antibody formation.
Explore preliminary clinical activity.

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Study Completion (ACTUAL): September 1, 2006

Study Registration Dates

• First Submitted: April 11, 2005
• First Submitted That Met QC Criteria: April 11, 2005
• First Posted (ESTIMATE): April 12, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): July 14, 2009
• Last Update Submitted That Met QC Criteria: July 10, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Carcinoma; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: 201-20