A Phase I/II Study of Interferon-Beta Gene Transfer (Ad.hIFN-β) in the Treatment of Refractory Colorectal Carcinoma With Liver Metastases
- Subjects with histologically confirmed hepatic metastases from primary colorectal
- 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.
- 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
- 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.