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

NCT ID: NCT00667628

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-24
• Study Completion Date: 2009-12-22

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.

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.

Conditions

Advanced Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

TAC-101

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.

Group Type: EXPERIMENTAL

TAC-101

Intervention Type: 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.

Interventions

TAC-101

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Quintiles, Inc.

INDUSTRY

Sponsor Role: collaborator

Taiho Oncology, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Taiho Central, MD

Role: STUDY_DIRECTOR

Taiho Oncology, Inc.

Locations

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, Japan

National hospital organization Shikoku Cancer Center

Matsuyama, Ehime, Japan

Fukuoka University Hospital

Jonan-ku, Fukuoka, Japan

Kurume University Hospital

Kurume, Fukuoka, Japan

Ogaki Municipal Hospital

Oogaki, Gifu, Japan

Fukuyama City Hospital

Fukuyama, Hiroshima, Japan

Asahikawa-Kosei General Hospital

Asahikawa, Hokkaido, Japan

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

The Hospital of Hyogo College of Medicine

Hishinomiya, Hyōgo, Japan

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, Japan

Iwate Medical University Hospital

Morioka, Iwate, Japan

Yokohama City University Medical Center

Yokohama, Kanagawa, Japan

Mie University Hospital

Tsu, Mie-ken, Japan

Nara Medical University Hospital

Kashihara, Nara, Japan

Okayama University Hospital

Shikata-cho, Okayama-ken, Japan

Osaka City University Hospital

Abeno-ku, Osaka, Japan

Osaka medical Center for Cancer and Cardiovascular Diseases

Higashinari-ku, Osaka, Japan

Osaka City General Hospital

Miyakojima-ku, Osaka, Japan

Kansai Medical Univesity Takii Hospital

Moriguchi, Osaka, Japan

Kinki University Hospital

Ōsaka-sayama, Osaka, Japan

Osaka Red Cross Hospital

Tennoji-ku, Osaka, Japan

Shizuoka Cancer Center Hospital

Sunto-gun, Shizuoka, Japan

The University of Tokyo Hospital

Bunkyo-ku, Tokyo, Japan

Kyoundo Hospital

Chiyoda City, Tokyo, Japan

Tochigi Cancer Center

Chiyoda-ku, Tokyo, Japan

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Wakayama Medical University Hospital

Kimiidera, Wakayama, Japan

Kochi Health Science Center

Kochi, , Japan

Kumamoto University Hospital

Kumamoto, , Japan

Countries

Japan

Other Identifiers

TAC101-203

Identifier Type: -

Identifier Source: org_study_id