RATIONALE: TAC-101 may stop the growth of cancer by stopping blood flow to the tumor.
PURPOSE: This phase I/II trial is studying the side effects and best dose of TAC-101 and to
see how well it works in treating patients with advanced hepatocellular carcinoma (liver
- Determine the maximum tolerated dose (MTD) of TAC-101 in patients with advanced
- Determine the safety of 2 consecutive courses of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
- Determine the toxic and adverse effects profile of this drug in these patients.
- Determine the objective antitumor response rate in patients treated with this drug
at the MTD.
- Determine the overall survival time of patients treated with this drug.
- Determine the time to disease progression in patients treated with this drug.
- Determine the duration of observed objective response, using WHO criteria and
measurements of serum alpha-fetoprotein concentrations, in patients treated with
- Determine the time to treatment failure in patients treated with this drug.
- Determine the safety and tolerability of intermittent treatment with this drug in
OUTLINE: This is an open-label, dose-escalation study.
- Phase I: Patients receive oral TAC-101 once daily on days 1-14. Treatment repeats every
21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 6 patients receive escalating doses of TAC-101 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients
experience dose-limiting toxicity.
- Phase II: Patients receive oral TAC-101 at the MTD (determined in phase I) once daily
on days 1-14. Courses repeat every 21 days in the absence of disease progression or
Patients are followed at 35-60 days.
PROJECTED ACCRUAL: A total of 6-18 patients for the phase I portion and 21-41 patients for
the phase II portion will be accrued for this study.
- 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
- 18 to 80
- ECOG 0-2
- More than 12 weeks
- 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
- 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
- Creatinine ≤ 1.5 times ULN
- 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)
- No prior pulmonary embolism
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception, except oral contraceptives
- 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:
- No prior thalidomide
- No prior putative antiangiogenesis therapy
- Prior interferon allowed
- No more than 2 prior chemotherapy regimens
- No concurrent estrogen products
- 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
- Not specified
- 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
- No concurrent azoles or tetracyclines
- No concurrent medications known or suspected to increase risk of venous
- No other concurrent retinoids