RATIONALE: TAC-101 may stop the growth of cancer by stopping blood flow to the tumor.

PURPOSE: Phase I/II trial to study the effectiveness of TAC-101 in treating patients who have advanced hepatocellular carcinoma (liver cancer).

Condition	Treatment or Intervention	Phase
advanced adult primary liver cancer recurrent adult primary liver cancer adult primary hepatocellular carcinoma localized unresectable adult primary liver cancer	Drug: TAC-101  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: growth factor antagonist therapy	Phase I Phase II

Further Study Details: 

OBJECTIVES: Phase I

• Primary
• Determine the maximum tolerated dose (MTD) of TAC-101 in patients with advanced hepatocellular carcinoma.
• 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.

Phase II

• Primary
• Determine the objective antitumor response rate in patients treated with this drug at the MTD.
• Secondary
• 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 this drug.
• Determine the time to treatment failure in patients treated with this drug.
• Determine the safety and tolerability of intermittent treatment with this drug in these patients.

OUTLINE: This is an open-label, dose-escalation study.

• 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 unacceptable toxicity. 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.

Ages Eligible for Study:  18 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

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

Texas
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting

Study chairs or principal investigators

Melanie B. Thomas, MD,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000349508; MDA-ID-01007; TAIHO-TAC101; NCI-1528; NCT00077142
Record last reviewed:  January 2004
Last Updated:  February 7, 2005
Record first received:  February 10, 2004
ClinicalTrials.gov Identifier:  NCT00077142
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08