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

October 30, 2018 updated by: M.D. Anderson Cancer Center

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)
Taiho Pharmaceutical Co., Ltd.

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2001

Primary Completion (Actual)

July 1, 2005

Study Completion (Actual)

August 1, 2005

Study Registration Dates

First Submitted

February 10, 2004

First Submitted That Met QC Criteria

February 10, 2004

First Posted (Estimate)

February 11, 2004

Study Record Updates

Last Update Posted (Actual)

October 31, 2018

Last Update Submitted That Met QC Criteria

October 30, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ID01-007
  • P30CA016672 (U.S. NIH Grant/Contract)
  • MDA-ID-01007 (Other Identifier: UT MD Anderson Cancer Center)
  • TAIHO-TAC101
  • NCI-1528
  • CDR0000349508 (Registry Identifier: NCI PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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