Phase 2 Study of TAC-101 Combined With Transcatheter Arterial Chemoembolization (TACE) Versus TACE Alone in Japanese Patients With Advanced Hepatocellular Carcinoma

This study has been terminated.
(Terminated due to safety concerns.)
Sponsor:
Collaborator:
Quintiles
Information provided by (Responsible Party):
Taiho Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT00667628
First received: April 24, 2008
Last updated: June 4, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to determine whether TAC-101 combined with Transcatheter Arterial Chemoembolization (TACE) is more effective than TACE alone in slowing tumor activity in patients with advanced hepatocellular carcinoma. The study is also looking at the safety of TAC-101 in combination with TACE.


Condition Intervention Phase
Advanced Hepatocellular Carcinoma
Drug: TAC-101
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of TAC-101 in Combination With Transcatheter Arterial Chemoembolization (TACE) Versus TACE Alone in Japanese Patients With Advanced Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by Taiho Oncology, Inc.:

Primary Outcome Measures:
  • Time to appearance of new lesions (TTNL) [ Time Frame: Tumor imaging will be conducted at screening/baseline, every 9 weeks during treatment, every 9 weeks during follow-up period until new lesions are observed or the end of study is reached ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: Survival status obtained at 30-day f/up visit, every 9 wks during imaging f/-up period, and following new lesions or initiation of another clinical trial, pts contacted every 12 wks until death or for at least 3 yrs after randomization of the last pt ] [ Designated as safety issue: No ]
  • Radiologic progression-free survival (PFS) [ Time Frame: Tumor imaging conducted at screening/baseline, every 9 wks during treatment, every 9 wks during follow-up period until new lesions are observed or the end of study is reached ] [ Designated as safety issue: No ]
  • Objective tumor response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: Tumor imaging will be conducted at screening/baseline, every 9 wks during treatment, every 9 wks during follow-up period until new lesions are observed or the end of study is reached ] [ Designated as safety issue: No ]
  • Effects on plasma levels of the tumor marker alpha-fetoprotein (AFP) [ Time Frame: Blood samples for AFP assessment obtained at Screening/ Baseline; every 9 wks after first TACE during the treatment period; at the end of the treatment period; and every 9 wks (± 1 wk) from first TACE during imaging f/up period ] [ Designated as safety issue: No ]
  • Adverse event profile and tolerability of TACE with TAC-101 therapy versus TACE with placebo therapy [ Time Frame: AEs will be reported from the time a patient signs ICF through the period of patient follow-up (30 days after the last dose of study medication) ] [ Designated as safety issue: Yes ]
  • The relationship between the PK of TAC-101 and its metabolites (blood sampling for PK is optional), and safety and efficacy parameters, including hepatic function [ Time Frame: Pharmacokinetic blood samples will be collected at 4 hours (± 1 hour), 8 hours (± 1 hour), and 24 hours (± 1 hour) post-dose on Day 1 of treatment Cycle 1. The 24-hour sample must be collected prior to dosing on Day 2 ] [ Designated as safety issue: No ]
  • The effects on selected RAR-related factors and a selected growth factor [ Time Frame: Blood samples collected at Screening/Baseline; every 9 wks (± 1 wk) after first TACE during the treatment period; at the end of the treatment period; at the Safety Follow-up visit (30 days after the end of study treatment) ] [ Designated as safety issue: No ]

Enrollment: 52
Study Start Date: April 2008
Study Completion Date: April 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Patients will receive TAC-101 20 mg (2 x 10-mg formulated tablets) administered orally every day with approximately 8 oz. water within 1 hour following a morning meal for 14 days followed by a 7-day recovery period, repeated every 21 days
Drug: TAC-101
Patients will receive TAC-101 20 mg (2 x 10-mg formulated tablets) administered orally every day with approximately 8 oz. water within 1 hour following a morning meal for 14 days followed by a 7-day recovery period, repeated every 21 days.
Placebo Comparator: B
Patients will receive placebo (two matching tablets) at same frequency and duration of active treatment
Drug: Placebo
Patients will receive placebo (two matching tablets) at same frequency and duration of active treatment

Detailed Description:

Advanced metastatic hepatocellular carcinoma (HCC) is not treatable by surgical approaches or locoregional therapies such as hepatic artery hemoembolization or radiofrequency ablation (RFA) which are effective in controlling localized tumors. Transcatheter arterial chemoembolization (TACE) is the most commonly performed procedure in the treatment of unresectable liver tumors for selected patients. The TACE procedure delivers highly concentrated drugs to the tumor itself and arrests blood flow. Most patients will have intrahepatic recurrence of their tumors following TACE. Studies of TAC-101, a synthetic retinoid, indicate that although TAC-101 may not induce tumor regression, it appears to have a stabilizing effect, prolonging survival over what was expected historically. This study is designed as a randomized, double-blind, placebo-controlled, parallel-group, phase 2 study in patients with advanced HCC who have undergone a TACE procedure, which will be conducted at multiple sites in Japan, to determine if administration of TAC-101 will enhance the benefits of the TACE procedure.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • A patient must meet all of the following inclusion criteria to be eligible for enrollment in this study and before undergoing the first TACE procedure of this study:

    1. Has an HCC diagnosis by histology or by the following non-invasive criteria observed either at enrollment or in the past.

      • One imaging technique (CT scan or magnetic resonance imaging [MRI] both with unenhanced plus hepatic arterial phase and portal venous phases) showing characteristic features in a focal lesion > 20 mm with arterial vascularization
      • Two dynamic imaging techniques (CT scan, MRI with unenhanced plus hepatic arterial phase and portal venous phases) showing characteristic features coincidentally in a focal lesion 10-20 mm with arterial vascularization.
    2. Is TACE naïve or has received the most recent TACE procedure at least 120 days before signing ICF.
    3. Eligible to receive TACE and being scheduled to receive TACE.
    4. Must be ≥ 20 years of age.
    5. Is not amenable to treatment with curative surgery, transplant, or percutaneous ablation, including RFA, percutaneous ethanol injection therapy (PEIT) and percutaneous microwave coagulation therapy (PMCT).
    6. Must have lesions in the liver that are confirmed nodular type with demonstrated substantial hypervascularity by CT scan or MRI both with unenhanced plus hepatic arterial phase and portal venous phases performed prior to first TACE in this study with the following tumor features:

      • If there are ≥ 4 intrahepatic lesions, all lesions can be < 30 mm. or, regardless of the number of lesions, the longest diameter of at least one intrahepatic lesion is ≥ 30 mm).
      • No vascular invasion in main trunk and first order branch of portal vein.
      • No extrahepatic tumor spread. The absence of extrahepatic abdominal tumors must be confirmed.
    7. Has adequate organ function as defined by the following criteria: White blood cell (WBC) count > 3,000/mm3; Platelet count > 60,000/mm3; Hemoglobin > 8.0 grams (g)/deciliter (dL); Aspartate transaminase (AST) < 5 x upper limit of normal (ULN); Alanine transaminase (ALT) < 5 x ULN; Total bilirubin < 2.0 mg/dL; Albumin ≥ 2.8 g/dL; Serum creatinine ≤ 1.5 mg/dL; International normalized ratio (INR) ≤ 2.0; Triglyceride ≤ 2.5 x ULN.
    8. Must have a Child-Pugh classification of ≤ 8.
    9. Must have a Cancer of the Liver Italian Program (CLIP)60 score of 0, 1, 2 or 3 (Appendix B).
    10. Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
    11. Must be willing and able to comply with schedule visits, treatment plans, laboratory tests, and other study procedures.
    12. Must provide written informed consent prior to the implementation of any study assessment or procedures.

Exclusion Criteria:

  • Patients will be excluded from participation in the study if any of the following conditions are observed before undergoing the first TACE procedure:

    1. Patient has longest diameter of intrahepatic lesion ≥ 100 mm.
    2. Patient has only infiltration type of HCC.
    3. Patient has extrahepatic metastasis of HCC including regional lymph node metastases (including in lymph nodes and organs).
    4. Patient had systemic chemotherapy (eg, sorafenib, doxorubicin), immunotherapy, or biologic therapy or radiotherapy for HCC, or treatment with TAC-101.
    5. Patient received treatment with any of the following within the specified time frame: Any major surgical procedure within 28 days prior to signing the ICF; Any transfusion, treatment with blood component preparation, albumin preparation, and granulocyte colony stimulating factor (G-CSF) within 14 days prior to signing the ICF; Any local therapy such as alcohol injection, radiofrequency/ultrasound ablation, intraarterial chemotherapy (transcatheter arterial injection) for HCC performed within 28 days prior to signing the ICF; Any investigational agent within 28 days prior to signing the ICF.
    6. Patient has ascites, pleural effusions or pericardial fluid refractory to diuretic therapy.
    7. Patient has clinical symptoms of hepatic encephalopathy.
    8. Patient has active or uncontrolled clinically serious infection excluding chronic hepatitis.
    9. Patient has a history of gastrointestinal (GI) bleeding in last 3 months.
    10. Patient has previous or concurrent malignancy except for in situ carcinoma of the cervix, or other solid tumor treated curatively and without evidence of recurrence for at least 3 years prior to the study.
    11. Patient has uncontrolled metabolic disorders or other nonmalignant organ or systemic diseases or secondary effects of cancer that induce a high medical risk and/or make assessment of survival uncertain.
    12. Patient has any history of deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI), cerebrovascular accident (CVA), transient ischemic attack (TIA), unstable angina pectoris, or any other significant thromboembolic event (TE) during the last 3 years.
    13. Patient has clinically significant electrocardiogram (ECG) abnormality.
    14. Patient has GI disease resulting in an inability to take oral medication.
    15. Patient has known allergy or hypersensitivity to TAC-101, doxorubicin, epirubicin, other anthracyclines, anthracenediones or any of the components used in the study drug formulations.
    16. Patient has known hypersensitivity to iodinated contrast medium.
    17. Patient is receiving therapeutic regimens of anticoagulants. However, use of low dose anticoagulants for prophylactic care of indwelling venous access device is permitted.
    18. Patient is taking medication known or suspected to predispose patient to an increased risk of VTE (eg, oral contraceptives, hormone replacement therapy, megestrol acetate).
    19. Patient is taking azoles or tetracyclines, because of the potential for drug interactions.
    20. Women who intend to become pregnant or are pregnant or lactating and men able to procreate that refuse to use a highly effective method of birth control during treatment with study medication and up to 6 months thereafter.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00667628

Locations
Japan
Aichi Cancer Center Hospital
Nagoya, Aichi, Japan, 464-8681
National hospital organization Shikoku Cancer Center
Matsuyama, Ehime, Japan, 791-0280
Fukuoka University Hospital
Jonan-ku, Fukuoka, Japan, 814-0180
Kurume University Hospital
Kurume, Fukuoka, Japan, 831-0011
Ogaki Municipal Hospital
Oogaki, Gifu, Japan, 503-8502
Fukuyama City Hospital
Fukuyama, Hiroshima, Japan, 721-8511
Asahikawa-Kosei General Hospital
Asahikawa, Hokkaido, Japan, 078-8211
Hokkaido University Hospital
Sapporo, Hokkaido, Japan, 060-8648
The Hospital of Hyogo College of Medicine
Hishinomiya, Hyogo, Japan, 663-8501
Kanazawa University Hospital
Kanazawa, Ishikawa, Japan, 920-8641
Iwate Medical University Hospital
Morioka, Iwate, Japan, 020-8505
Yokohama City University Medical Center
Yokohama, Kanagawa, Japan, 232-0024
Mie University Hospital
Tsu, Mie, Japan, 514-8507
Nara Medical University Hospital
Kashihara, Nara, Japan, 634-8522
Okayama University Hospital
Shikata-cho, Okayama, Japan, 700-8558
Osaka City University Hospital
Abeno-ku, Osaka, Japan, 545-8586
Osaka medical Center for Cancer and Cardiovascular Diseases
Higashinari-ku, Osaka, Japan, 537-8511
Osaka City General Hospital
Miyakojima-ku, Osaka, Japan, 534-0021
Kansai Medical Univesity Takii Hospital
Moriguchi, Osaka, Japan, 570-8507
Kinki University Hospital
Osaka-sayama, Osaka, Japan, 589-8511
Osaka Red Cross Hospital
Tennoji-ku, Osaka, Japan, 543-8555
Shizuoka Cancer Center Hospital
Sunto-gun, Shizuoka, Japan, 411-8777
The University of Tokyo Hospital
Bunkyo-ku, Tokyo, Japan, 113-8655
Kyoundo Hospital
Chiyoda, Tokyo, Japan, 101-0062
Tochigi Cancer Center
Chiyoda-ku, Tokyo, Japan, 101-0047
National Cancer Center Hospital
Chuo-ku, Tokyo, Japan, 104-0045
Wakayama Medical University Hospital
Kimidera, Wakayama, Japan, 641-8510
Kochi Health Science Center
Kochi, Japan, 781-8555
Kumamoto University Hospital
Kumamoto, Japan, 860-8556
Sponsors and Collaborators
Taiho Oncology, Inc.
Quintiles
Investigators
Study Director: Fabio Benedetti, MD Taiho Oncology, Inc.
  More Information

No publications provided

Responsible Party: Taiho Oncology, Inc.
ClinicalTrials.gov Identifier: NCT00667628     History of Changes
Other Study ID Numbers: TAC101-203
Study First Received: April 24, 2008
Last Updated: June 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on August 21, 2014