RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Randomized phase II trial to compare the effectiveness of SCH 66336 with or without gemcitabine followed by surgery with that of surgery alone in treating patients who have primary liver cancer.

Condition	Treatment or Intervention	Phase
recurrent adult primary liver cancer localized resectable adult primary liver cancer adult primary hepatocellular carcinoma adult primary cholangiocellular carcinoma	Drug: gemcitabine  Drug: SCH 66336	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the biologic activity and toxicity of neoadjuvant SCH 66336 with or without gemcitabine followed by surgical resection vs surgical resection alone in patients with resectable primary liver cancer.

PROTOCOL OUTLINE: This is a randomized, open-label study. Patients are randomized to one of three treatment arms. Arm I: Patients receive neoadjuvant oral SCH 66336 twice daily for 14 days followed by surgical resection. Arm II: Patients receive neoadjuvant oral SCH 66336 twice daily for 14 days and gemcitabine IV over 30 minutes once weekly for 2 weeks followed by surgical resection. Arm III: Patients undergo surgical resection. Patients receive no neoadjuvant therapy prior to resection.

PROJECTED ACCRUAL: Approximately 30 patients (10 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically or cytologically confirmed resectable primary hepatocellular carcinoma or cholangiocarcinoma
• No metastatic disease to the liver

--Prior/Concurrent Therapy--

• Biologic therapy: No concurrent immunotherapy
• Chemotherapy: No other concurrent chemotherapy
• Endocrine therapy: No concurrent hormonal therapy including estrogen therapy; No concurrent oral contraceptives or other hormonal methods; Concurrent megestrol acetate allowed; No concurrent corticosteroids (except for nausea/vomiting during gemcitabine administration)
• Radiotherapy: At least 6 weeks since prior radiotherapy and recovered; No concurrent radiotherapy
• Surgery: See Disease Characteristics; At least 6 weeks since prior surgery and recovered
• Other: At least 6 weeks since prior systemic therapy and recovered; No 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); No concurrent HIV protease inhibitors (e.g., amprenavir, ritonavir, or saquinavir mesylate); No concurrent cisapride; No other concurrent investigational therapy

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 70-100%
• Life expectancy: Not specified
• 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: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective barrier contraception; No malabsorption or other gastrointestinal (GI) condition that would preclude ability to take oral medication and/or GI absorption (e.g., partial small bowel obstruction); No non-malignant systemic disease that would preclude study; No active uncontrolled infection; No grade II nausea or grade I vomiting despite antiemetic medication

Study chairs or principal investigators

Rafael G. Amado,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000068712; UCLA-0002038; NCI-G01-1958
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  July 11, 2001
ClinicalTrials.gov Identifier:  NCT00020774
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08