Phase I/II Dose Escalation, Pharmacokinetic, Safety, and Efficacy Study of Oral TAC-101 in Patients With Advanced Hepatocellular Carcinoma
TAC-101
Adenocarcinoma+8
+ Carcinoma
+ Digestive System Diseases
Treatment Study
Summary
Study start date: April 1, 2001
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.37 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 18 to 80 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy Objectives
Primary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location