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

Colorectal Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00107861
• Other study ID #: 201-20
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 11, 2005
• Last updated: July 10, 2009
• Start date: May 2005
• Est. completion date: September 2006

Study information

• Verified date: July 2009
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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-ß.

• Any prior treatment with a gene delivery vector or an adenovirus therapeutic agent.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Colorectal Carcinoma
• Colorectal Neoplasms
• Metastases
• Neoplasm Metastasis

Intervention

Drug:
• Ad.hIFN-ß (BG00001, IDEC-201)

Locations

Country	Name	City	State
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	University of California San Diego	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	- Evaluate the safety of a single IV administration of Ad.hIFN-ß.
Secondary	Evaluate the MTD or maximum feasible dose (MFD) of Ad.hIFN-ß.
Secondary	Evaluate IFN-ß and Ad.hIFN-ß vector serum concentrations.
Secondary	Evaluate immunogenicity of Ad.hIFN-ß by measuring human anti adenovirus and human anti-IFN-ß antibody formation.
Secondary	Explore preliminary clinical activity.