Study of TAC-101 as Second Line Treatment in Patients With Advanced Hepatocellular Carcinoma Who Received Sorafenib as First Line Therapy

NCT00687596 | Terminated Phase 2 Results

• 1 other identifier: TAC101-202
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether TAC-101 as a second line therapy for participants who received Sorafenib as first line therapy is effective in slowing tumor activity in patients with advanced hepatocellular carcinoma. The study is also looking at the safety of TAC-101 following treatment with Sorafenib.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS was defined as the time from the date of randomization to the date of death. Participants who were still alive were censored at the date last known to be alive (last contact date or last follow-up visit).

  From the date of randomization to date of death or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)

Secondary Outcomes (15)

• Radiologic Progression-free Survival (PFS)

  From the date of randomization to date of tumor disease progression or death or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)

• Time To Progression (TTP)

  From the date of randomization to date of tumor disease progression or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)

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

  From Baseline up to 30 days after the last dose (maximum duration: up to 7.2 months for Placebo and up to 7.9 months for TAC-101)

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

  From the date of randomization to date of tumor disease progression or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)

• Percent Change From Baseline in Plasma Levels of the Tumor Marker Alpha Fetoprotein-L3 (AFP-L3)

  From the date of randomization to date of tumor disease progression or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)

Study Arms (2)

TAC-101

EXPERIMENTAL

Participants with advanced hepatocellular carcinoma who had previously received Sorafenib (as first line therapy) were administered a dose of 20 milligram per day (mg/day) of TAC-101 (as second line treatment) oral tablets within 1 hour post morning meals on Days 1 to 14 followed by a recovery period on Days 15 to 21 in 21-day cycle until disease progression or participant met a treatment discontinuation criterion.

Drug: TAC-101

Placebo

PLACEBO COMPARATOR

Participants with advanced hepatocellular carcinoma who had previously received Sorafenib (as first line therapy) were administered a matching placebo for TAC-101 oral tablets within 1 hour post morning meals on Days 1 to 14 followed by a recovery period from on 15 to 21 in 21-day cycle until disease progression or participant met a treatment discontinuation criterion.

Drug: Placebo

Interventions

TAC-101 DRUG

Participants were randomized to TAC 101 received TAC 101 20 mg (administered as 2 10 mg formulated tablets) PO daily with approximately 240 mL (8 oz) of water under fed conditions (no later than 1 hour after a meal) for 14 days followed by a 7 day recovery period. This cycle was repeated every 21 days.

TAC-101

Placebo DRUG

Participants randomized to placebo received 2 placebo tablets (identical in appearance to the TAC 101 tablets) administered PO daily with approximately 240 mL (8 oz) of water under fed conditions (no later than 1 hour after a meal) in a regimen identical to that for TAC 101.

Placebo

Eligibility Criteria

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

You may qualify if:

• Provide written informed consent prior to performance of any study procedures.
• Is at least 18 years of age.
• Have a diagnosis of advanced unresectable histologically confirmed HCC (excluding fibrolamellar carcinoma).
• Have discontinued from first line treatment with sorafenib monotherapy for any reason (ie, tumor disease progression, intolerance) at least 14 days prior to planned randomization but have not received any second line treatment for HCC.
• Have recovered from any significant sorafenib-related treatment toxicities prior to randomization (Grade 1).
• Have at least 1 target lesion that is viable (has vascularization) and can be accurately measured according to RECIST.
• Patients who have received local therapy prior to sorafenib administration (radiation, surgery, hepatic arterial embolization, chemoembolization, RFA, percutaneous ethanol injection \[PEI\] or cryoablation) are eligible. Local therapy must be completed at least 4 weeks prior to the baseline scan.
• Have ECOG score of 0, 1, or 2.
• Child-Pugh score \<8.
• Have adequate organ function defined as:
• Platelet count great than 50, less than 109/L;
• Hemoglobin 8.0 g/dL;
• Total bilirubin 3 mg/dL;
• Alanine transaminase (ALT) and aspartate aminotransferase (AST) less than or equal to 5 X ULN;
• Serum creatinine 1.5 X ULN;

You may not qualify if:

• History of DVT, PE, myocardial infarction (MI), CVA, transitory ischemic attack (TIA), or any other significant TE during the last 3 years.
• Have clinically significant symptoms of hepatic encephalopathy or known brain metastasis.
• Patients who have had clinically significant acute gastrointestinal bleeding as a result of portal vein hypertension within 4 weeks prior to randomization are excluded; however, patients with a history of acute gastrointestinal bleeding that have received appropriate treatment, ie, ligation of varices, are eligible.
• Are receiving therapeutic regimens of anticoagulants, with the exception of prophylaxis care of indwelling venous access devices.
• Have received a liver transplant.
• Are taking prohibited medication.
• Have had treatment with any of the following within the specified timeframe prior to randomization:
• Any sorafenib within the 14 days prior to randomization.
• Major surgery within the 4 weeks prior to randomization.
• Any transfusion, treatment with blood component preparation, received. erythropoietin , albumin preparation, and granulocyte colony-stimulating factor (G CSF) within the 2 weeks prior to randomization.
• Has a serious illness or medical condition(s) including, but not limited to the following:
• Known gastrointestinal disorder, including malabsorption, chronic nausea, vomiting, or diarrhea present to the extent that it might interfere with oral intake and absorption of the study medication.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
• Previous or concurrent malignancy except for basal cell carcinoma and/or 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.
• 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.

Sponsors & Collaborators

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

Study Sites (1)

I.R.C.C.S. San Matteo University Hospital, Golgi

Pavia, 27100, Italy

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

TAC 101

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Limitations and Caveats

Study was prematurely terminated by Sponsor due to unexpected higher occurrence of thromboembolic events on 06-May-2009. PK \& biomarker assessments were optional and explorative,and were not conducted and evaluated due to limited participants count.

Results Point of Contact

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

medicalinformation@taihooncology.com

+1 844-878-2446

Study Officials

• Taiho Central

  Taiho Oncology, Inc. USA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• 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: May 28, 2008
• First Posted: June 2, 2008
• Study Start: August 1, 2008
• Primary Completion: May 10, 2010
• Study Completion: May 10, 2010
• Last Updated: September 19, 2024
• Results First Posted: February 1, 2022

Record last verified: 2024-08

Locations

IT (1)