Phase I/II Dose Escalation, Pharmacokinetic, Safety, and Efficacy Study of Oral TAC-101 in Patients With Advanced Hepatocellular Carcinoma

Date de début de l'étude : 1 avril 2001

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed hepatocellular carcinoma * At least 1 previously unirradiated, bidimensionally measurable lesion greater than 20 mm by MRI or conventional CT scan OR at least 10 mm by spiral CT scan * Patients with CNS involvement must have completed appropriate treatment and have no progressive neurologic deficits within the past 28 days * No carcinomatous meningitis PATIENT CHARACTERISTICS: Age * 18 to 80 Performance status * ECOG 0-2 Life expectancy * More than 12 weeks Hematopoietic * Hemoglobin ≥ 10.0 g/dL * WBC ≥ 2,000/mm\^3 * Absolute neutrophil count ≥ 1,000/mm\^3 * Platelet count ≥ 40,000/mm\^3 * No abnormal bleeding or clotting Hepatic * No grade C Child-Pugh cirrhosis * AST and ALT ≤ 2.5 times upper limit of normal (ULN) * Albumin ≥ 2.8 g/dL * INR ≤ 1.5 times ULN * Bilirubin ≤ 2.0 mg/dL Renal * Creatinine ≤ 1.5 times ULN Cardiovascular * No prior deep vein thrombosis * No prior superficial venous thrombosis * No family history of thromboembolism in a first-degree relative * No lower extremity thromboses by Doppler ultrasound (unless a subsequent venous angiography confirms a false positive ultrasound) Pulmonary * No prior pulmonary embolism Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception, except oral contraceptives containing estrogen * Fasting triglycerides ≤ 400 mg/dL for men or ≤ 325 mg/dL for women * No other malignancy within the past 3 years except inactive nonmelanoma skin cancer or carcinoma in situ of the cervix * No uncontrolled metabolic disorders, other nonmalignant organ or systemic disease, or secondary effects of cancer that induce a high medical risk * No known allergy or hypersensitivity to TAC-101 or its components PRIOR CONCURRENT THERAPY: Biologic therapy * No prior thalidomide * No prior putative antiangiogenesis therapy * Prior interferon allowed Chemotherapy * No more than 2 prior chemotherapy regimens Endocrine therapy * No concurrent estrogen products Radiotherapy * See Disease Characteristics * More than 21 days since prior radiotherapy, except small portal radiotherapy used for the palliation of isolated, symptomatic, osseous metastases * No prior radiotherapy to evaluable lesions * No concurrent radiotherapy unless for bone pain that is present before beginning study Surgery * Not specified Other * Prior anticancer treatment allowed provided there is clear evidence of progressive disease after the most recent treatment * More than 21 days since prior anticancer therapy and recovered * No more than 2 prior treatment regimens * No concurrent therapeutic anticoagulants * Concurrent low-dose warfarin for prophylactic care of indwelling venous access devices allowed * No concurrent azoles or tetracyclines * No concurrent medications known or suspected to increase risk of venous thromboembolism * No other concurrent retinoids