SCH 66336 With or Without Gemcitabine Followed by Surgery Compared With Surgery Alone in Treating Patients With Primary Liver Cancer

• Histologically or cytologically confirmed resectable primary hepatocellular carcinoma or cholangiocarcinoma
• 18 and over
• Karnofsky 70-100%
• Hematopoietic: Absolute neutrophil count greater than 1,500/mm3
• Platelet count at least 100,000/mm3
• Hemoglobin at least 9 g/dL Hepatic:
• Bilirubin no greater than 2 times upper limit of normal (ULN) SGOT or SGPT no greater than 5 times ULN
• Albumin at least 2.5 g/dL INR less than 1.3 Renal:
• Creatinine no greater than 1.5 mg/dL
• Cardiovascular: QTc prolongation no greater than 440 msec Other:
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• At least 6 weeks since prior radiotherapy and recovered
• At least 6 weeks since prior surgery and recovered
• At least 6 weeks since prior systemic therapy and recovered

Exclusion Criteria:

• metastatic disease outside of the liver
• pregnant or nursing
• malabsorption or other gastrointestinal (GI) condition that would preclude ability to take oral medication and/or GI absorption (e.g., partial small bowel obstruction)
• non-malignant systemic disease that would preclude study
• active uncontrolled infection No grade II nausea or grade I vomiting despite antiemetic medication
• concurrent immunotherapy Chemotherapy: No other concurrent chemotherapy
• concurrent hormonal therapy including estrogen therapy
• concurrent oral contraceptives or other hormonal methods Concurrent megestrol acetate allowed
• concurrent corticosteroids (except for nausea/vomiting during gemcitabine administration)
• concurrent CYP3A4 inhibitors or inducers including: Azoles (e.g., itraconazole, clotrimazole, fluconazole, or ketoconazole) Macrolide antibiotics (e.g., azithromycin, clarithromycin, or erythromycin) Cyclosporine Grapefruit Antiepileptic medication (e.g., phenytoin, carbamazepine, or phenobarbital) Antibiotics for tuberculosis (e.g., rifampin or isoniazid)
• concurrent HIV protease inhibitors (e.g., amprenavir, ritonavir, or saquinavir mesylate)
• concurrent cisapride
• other concurrent investigational therapy