TAC-101 in Treating Patients With Advanced Hepatocellular Carcinoma (Liver Cancer)

Study Overview
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Brief Summary
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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 cancer).

Detailed Description
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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. 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 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.

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

Conditions
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Liver Cancer

Intervention / Treatment
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* Drug: TAC-101


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAC-101<br>Oral TAC-101 daily Days 1-14, repeats every 21 days for 2 courses. | Drug: TAC-101<br>* Once daily by mouth on days 1-14, repeat every 21 days for 2 courses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of TAC-101 |  | 60 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced adult primary liver cancer, recurrent adult primary liver cancer, adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer, Oral TAC-101