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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Colorectal Carcinoma, Metastases

Intervention / Treatment
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* Drug: Ad.hIFN-β (BG00001, IDEC-201)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Ad.hIFN-β (BG00001, IDEC-201)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - Evaluate the safety of a single IV administration of Ad.hIFN-β. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  |  |