interferon-beta gene transfer (ad.hifn-β) as treatment for refractory colorectal carcinoma with liver metastases

Conditions: Colorectal Carcinoma; Metastases

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.

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.

Eligibility criteria:
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.