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

NCT00667628 | Terminated Phase 2 Results

• 1 other identifier: TAC101-203
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 29

Brief Summary

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.

Conditions

Advanced Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Time to Appearance of New Lesions (TTNL)

  TTNL was defined as the time from the date of randomization to the date of appearance of a new lesion. Participants who had no appearance of new lesions had their TTNL censored at the date of their last tumor assessment.

  From randomization (within 14 days prior to first TACE) assessed every 9 weeks after first TACE to date of appearance of a new lesion or until cut-off date (22-Dec-2009) (up to approximately 20 months)

Secondary Outcomes (5)

• Overall Survival (OS)

  From randomization (within 14 days prior to first TACE) assessed every 9 weeks after first TACE until cut-off date of 22 Dec 2009 (up to approximately 20 months)

• Progression-Free Survival (PFS)

  From randomization (within 14 days prior to first TACE) assessed every 9 weeks after first TACE until cut-off date of 22 Dec 2009 (up to approximately 20 months)

• Objective Tumor Response Rate (ORR)

  From randomization (within 14 days prior to first TACE) assessed every 9 weeks after first TACE until cut-off date of 22 Dec 2009 (up to approximately 20 months)

• Change From Baseline in Plasma Levels of Tumor Marker Alpha-fetoprotein (AFP)

  Baseline, End of treatment (last dose of study medication, i.e., approximately 7 months)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

  From first dose of study drug up to 30 days after last dose of study drug or until the start of new anti-tumor therapy, whichever was earlier (up to approximately 8.5 months)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants were administered with placebo tablets matching to TAC-101 orally, every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) treatment recovery period. Repeated every 21 days cycle up to new lesions were observed or the participant met a treatment discontinuation criterion.

Drug: Placebo

TAC-101

EXPERIMENTAL

Participants were administered with TAC-101 tablets, 20 milligram per day (mg/day) orally for every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) recovery period (21-day Cycle). Repeated every 21 days cycle up to new lesions were observed or the participant met a treatment discontinuation criterion.

Drug: TAC-101

Interventions

TAC-101 DRUG

Participants received 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.

TAC-101

Placebo DRUG

Participants received placebo (two matching tablets) at same frequency and duration of active treatment.

Placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Is TACE naïve or has received the most recent TACE procedure at least 120 days before signing ICF.
• Eligible to receive TACE and being scheduled to receive TACE.
• Must be ≥ 20 years of age.
• 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).
• 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.
• 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.
• Must have a Child-Pugh classification of ≤ 8.
• Must have a Cancer of the Liver Italian Program (CLIP)60 score of 0, 1, 2 or 3 (Appendix B).
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

You may not qualify if:

• Patients will be excluded from participation in the study if any of the following conditions are observed before undergoing the first TACE procedure:
• Patient has longest diameter of intrahepatic lesion ≥ 100 mm.
• Patient has only infiltration type of HCC.
• Patient has extrahepatic metastasis of HCC including regional lymph node metastases (including in lymph nodes and organs).
• Patient had systemic chemotherapy (eg, sorafenib, doxorubicin), immunotherapy, or biologic therapy or radiotherapy for HCC, or treatment with TAC-101.
• 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.
• Patient has ascites, pleural effusions or pericardial fluid refractory to diuretic therapy.
• Patient has clinical symptoms of hepatic encephalopathy.
• Patient has active or uncontrolled clinically serious infection excluding chronic hepatitis.
• Patient has a history of gastrointestinal (GI) bleeding in last 3 months.
• 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.
• 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.
• 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.
• Patient has clinically significant electrocardiogram (ECG) abnormality.
• Patient has GI disease resulting in an inability to take oral medication.

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead
• Quintiles, Inc.: collaborator

Study Sites (29)

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, 464-8681, Japan

Location

National hospital organization Shikoku Cancer Center

Matsuyama, Ehime, 791-0280, Japan

Location

Fukuoka University Hospital

Jonan-ku, Fukuoka, 814-0180, Japan

Location

Kurume University Hospital

Kurume, Fukuoka, 831-0011, Japan

Location

Ogaki Municipal Hospital

Oogaki, Gifu, 503-8502, Japan

Location

Fukuyama City Hospital

Fukuyama, Hiroshima, 721-8511, Japan

Location

Asahikawa-Kosei General Hospital

Asahikawa, Hokkaido, 078-8211, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

The Hospital of Hyogo College of Medicine

Hishinomiya, Hyōgo, 663-8501, Japan

Location

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

Iwate Medical University Hospital

Morioka, Iwate, 020-8505, Japan

Location

Yokohama City University Medical Center

Yokohama, Kanagawa, 232-0024, Japan

Location

Mie University Hospital

Tsu, Mie-ken, 514-8507, Japan

Location

Nara Medical University Hospital

Kashihara, Nara, 634-8522, Japan

Location

Okayama University Hospital

Shikata-cho, Okayama-ken, 700-8558, Japan

Location

Osaka City University Hospital

Abeno-ku, Osaka, 545-8586, Japan

Location

Osaka medical Center for Cancer and Cardiovascular Diseases

Higashinari-ku, Osaka, 537-8511, Japan

Location

Osaka City General Hospital

Miyakojima-ku, Osaka, 534-0021, Japan

Location

Kansai Medical Univesity Takii Hospital

Moriguchi, Osaka, 570-8507, Japan

Location

Kinki University Hospital

Ōsaka-sayama, Osaka, 589-8511, Japan

Location

Osaka Red Cross Hospital

Tennoji-ku, Osaka, 543-8555, Japan

Location

Shizuoka Cancer Center Hospital

Sunto-gun, Shizuoka, 411-8777, Japan

Location

The University of Tokyo Hospital

Bunkyo-ku, Tokyo, 113-8655, Japan

Location

Kyoundo Hospital

Chiyoda City, Tokyo, 101-0062, Japan

Location

Tochigi Cancer Center

Chiyoda-ku, Tokyo, 101-0047, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Wakayama Medical University Hospital

Kimiidera, Wakayama, 641-8510, Japan

Location

Kochi Health Science Center

Kochi, 781-8555, Japan

Location

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

Location

MeSH Terms

Interventions

TAC 101

Limitations and Caveats

This study was terminated early due to the unexpected higher occurrence of thromboembolic events.

Results Point of Contact

• Title: Taiho Central
• Organization: Taiho Oncology, Inc.

medicalinformation@taihooncology.com

+1 844-878-2446

Study Officials

• Taiho Central, MD

  Taiho Oncology, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2008
• First Posted: April 28, 2008
• Study Start: April 24, 2008
• Primary Completion: December 22, 2009
• Study Completion: December 22, 2009
• Last Updated: September 19, 2024
• Results First Posted: April 15, 2022

Record last verified: 2024-08

Locations

JP (29)