Clinical Trial for GALNT14 Genotype - Guided, Sorafenib in Combination With TACE in Hepatocellular Carcinoma

NCT02504983 | Unknown Phase 4

• 1 other identifier: 104-1686A3
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Transcatheter arterial chemoembolization (TACE) + sorafenib therapy has been demonstrated to exert a beneficial effective on time-to-tumor-progression (TTP) in patients with unresectable hepatocellular carcinoma (HCC) in some studies. However, the beneficial effect varies among studies conducted in different areas of the world. The objectives of this study are (1) to understand whether GALNT14 TT genotype patients respond better than do GALNT14 non-TT genotype patients when treated by TACE; and (2) to understand whether GALNT14 non-TT genotype patients can benefit from TACE plus sorafenib (Nexavar) combination therapy. Patients enrolled will be stratified by GALNT14 genotyping. The GALNT14 "non-TT" patients were then randomized into two subgroups to evaluate the safety, tolerability and efficacy of TACE plus sorafenib therapy. The primary endpoint of this study is the efficacy of TACE with or without sorafenib combination therapy evaluated by complete remission (CR). The secondary endpoints are:

1. 1.Time to partial or complete response (PR + CR).
2. 2.Time-to-tumor-progression (TTP) and the progression free survival (PFS).
3. 3.Overall survival (OS).
4. 4.Safety and tolerability of TACE plus sorafenib therapy.

Conditions

Hepatocellular Carcinoma

Keywords

SNPs

Outcome Measures

Primary Outcomes (1)

• Complete remission

  3 years

Secondary Outcomes (5)

• Time to partial (including complete) response

  3 years

• Time-to-tumor-progression (TTP)

  3 years

• Progression free survival (PFS).

  3 years

• Overall survival (OS)

  3 years

• Safety and tolerability of TACE plus sorafenib therapy recorded and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.

  3 years

Study Arms (3)

GALNT14 TT

ACTIVE COMPARATOR

Patients will be treated by Transcatheter arterial chemoembolization every 12 ± 2 weeks dependent on CT evaluation. Before each TACE, dynamic CT will be performed for pre-treatment evaluation. When no viable tumor is seen on CT, TACE is to be discontinued.

Procedure: TACE

GALNT14 non-TT TACE alone

ACTIVE COMPARATOR

Patients will be treated by Transcatheter arterial chemoembolization every 12 ± 2 weeks dependent on CT evaluation. Before each TACE, dynamic CT will be performed for pre-treatment evaluation. When no viable tumor is seen on CT, TACE is to be discontinued.

Procedure: TACE

GALNT14 non-TT TACE plus sorafenib

EXPERIMENTAL

Patients will be treated by Transcatheter arterial chemoembolization every 12 ± 2 weeks dependent on CT evaluation, plus sorafenib adjuvant therapy. Before each TACE, dynamic CT will be performed for pre-treatment evaluation. When no viable tumor is seen on CT, TACE is to be discontinued. patients will receive sorafenib 400 mg/d between each TACE. Patient will start receiving Sorafenib on Day 4 (up to Day 7) after 1st TACE (Day 1) and will interrupt after evening dose 4 days before each next TACE and re-start Sorafenib on Day 4 (up to Day 7) after each TACE cycle.Additional sorafenib treatment is optional and will be judged by investigator in the subject's best medical interest.

Drug: sorafenib; Procedure: TACE

Interventions

sorafenib DRUG

sorafenib is an oral, multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma

Also known as: Nexavar

GALNT14 non-TT TACE plus sorafenib

TACE PROCEDURE

Transcatheter arterial chemoembolization was performed by the injection of small embolic particles coated with chemotherapeutic agents selectively into an artery directly supplying a tumor.

Also known as: Transcatheter arterial chemoembolization

GALNT14 TT; GALNT14 non-TT TACE alone; GALNT14 non-TT TACE plus sorafenib

Eligibility Criteria

• Age: 20 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed Diagnosis of HCC:
• Cirrhotic subjects: Clinical diagnosis by AASLD criteria HCC can be defined in cirrhotic subjects by one imaging technique (CT scan, MRI, or second generation contrast ultrasound) showing a nodule larger than 2cm with contrast uptake in the arterial phase and washout in venous or late phases, or two imaging techniques showing this radiological behaviour for nodules of 1-2cm in diameter Cytohistological confirmation is required for subjects who do not fulfill these eligibility criteria
• Non-cirrhotic subjects:
• For subjects without cirrhosis, histological confirmation is mandatory Documentation of original biopsy for diagnosis is acceptable
• Never received TACE/ chemotherapy/ radiotherapy or targeted agents prior to this study.
• Patients should be either in BCLC clinical stage B (multinodular asymptomatic tumors without extra-hepatic spread or portal vein invasion) with or without unilateral secondary or tertiary branches of portal vein invasion. Main portal vein invasion or extra-hepatic spread is not allowed.
• Child-Pugh functional class A or B.
• Measurable disease using mRECIST criteria. At least 1 measurable lesion must be present.
• ECOG performance status 0 to 1.
• Age \> 18 years
• Both men and women enrolled in this trial must use adequate birth control measures during the course of the trial and 4 weeks after the completion of trial
• Informed consent must be obtained prior to study initiation.
• Total bilirubin \< 3.0 mg/dL with no evidence of biliary tract obstruction.
• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 5 × upper limit of normal.
• Absolute neutrophil count \> 1000/mm3; Platelets ≧ 60x109/L.

You may not qualify if:

• BCLC stage A.
• Presence of extrahepatic metastasis.
• Child-Pugh score =C
• Significant cardiac disease.
• Serious bacteria infection requiring systemic antibiotics.
• Pregnancy
• Expected non-compliance.
• Uncontrolled illness including, but not limited to, ongoing infection, congestive hear failure, unstable angina pectoris, cardiac arryhythmia, or psychiatric illness.
• Bleeding esophageal or gastric varices within three months without ligation or sclerosis injection therapy.
• Subjects with known HIV infection.
• ECOG status \> or = 2

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Chang Gung Memorial Hospital

Taoyuan District, Taiwan

Location

Related Publications (2)

• Liang KH, Lin CL, Chen SF, Chiu CW, Yang PC, Chang ML, Lin CC, Sung KF, Yeh C, Hung CF, Chien RN, Yeh CT. GALNT14 genotype effectively predicts the therapeutic response in unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization. Pharmacogenomics. 2016 Mar;17(4):353-66. doi: 10.2217/pgs.15.179. Epub 2016 Feb 12.

  PMID: 26871639 RESULT

• Chen WT, Lin SM, Lee WC, Wu TJ, Lin CC, Shen CH, Chang ML, Lin CL, Yeh CT. GALNT14 genotype-guided chemoembolization plus sorafenib therapy in hepatocellular carcinoma: a randomized trial. Hepatol Int. 2022 Feb;16(1):148-158. doi: 10.1007/s12072-021-10283-7. Epub 2022 Jan 4.

  PMID: 34982369 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib

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

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Chau-Ting Yeh, MD/PhD

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2015
• First Posted: July 22, 2015
• Study Start: August 1, 2015
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2021
• Last Updated: February 5, 2020

Record last verified: 2020-02

Locations

TW (1)