Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Closed	18 to 80	Pharmaceutical / Industry	MDA-ID-01007 TAIHO-TAC101, NCI-1528, NCT00077142

Objectives

Phase I

Primary

1. Determine the maximum tolerated dose (MTD) of TAC-101 in patients with advanced hepatocellular carcinoma.
2. Determine the safety of 2 consecutive courses of this drug in these patients.
3. Determine the pharmacokinetics of this drug in these patients.
4. Determine the toxic and adverse effects profile of this drug in these patients.

Phase II

Primary

1. Determine the objective antitumor response rate in patients treated with this drug at the MTD.

Secondary

1. Determine the overall survival time of patients treated with this drug.
2. Determine the time to disease progression in patients treated with this drug.
3. Determine the duration of observed objective response, using WHO criteria and measurements of serum alpha-fetoprotein concentrations, in patients treated with this drug.
4. Determine the time to treatment failure in patients treated with this drug.
5. Determine the safety and tolerability of intermittent treatment with this drug in these patients.

Entry 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

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

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/mm³
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 40,000/mm³
• 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

Expected Enrollment

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.

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.

Higginbotham KB, Lozano R, Brown T, et al.: A phase I/II trial of TAC-101, an oral synthetic retinoid, in patients with advanced hepatocellular carcinoma. J Cancer Res Clin Oncol 134 (12): 1325-35, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Melanie Thomas, MD, Protocol chair(Contact information may not be current)		Ph: 713-792-2828; 800-392-1611

Registry Information
Official Title		Phase I/II Dose Escalation, Pharmacokinetic, Safety, and Efficacy Study of Oral TAC-101 in Patients with Advanced Hepatocellular Carcinoma
Trial Start Date		2001-04-24
Registered in ClinicalTrials.gov		NCT00077142
Date Submitted to PDQ		2003-12-11
Information Last Verified		2005-04-18
NCI Grant/Contract Number		P30-CA16672

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