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

Primary Purpose

Hepatocellular Carcinoma

Status

Unknown status

Phase

Phase 4

Locations

Taiwan

Study Type

Interventional

Intervention

sorafenib

TACE

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring SNPs

Eligibility Criteria

20 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
Serum creatinine < 2 x ULN.
Antiviral treatment for hepatitis B or C is allowed except for interferon.

Exclusion Criteria:

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

Sites / Locations

Chang Gung Memorial Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

GALNT14 TT

GALNT14 non-TT TACE alone

GALNT14 non-TT TACE plus sorafenib

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Complete remission

Secondary Outcome Measures

Time to partial (including complete) response

Time-to-tumor-progression (TTP)

Progression free survival (PFS).

Overall survival (OS)

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.

Full Information

NCT ID

NCT02504983

First Posted

July 16, 2015

Last Updated

February 4, 2020

Sponsor

Chang Gung Memorial Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02504983

Brief Title

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

Official Title

Randomized, Open Label, Clinical Trial for GALNT14 Genotype - Guided, Sorafenib in Combination With TACE Therapy in Hepatocellular Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Unknown status

Study Start Date

August 2015 (undefined)

Primary Completion Date

July 2021 (Anticipated)

Study Completion Date

July 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Chang Gung Memorial Hospital

4. Oversight

Data Monitoring Committee

5. Study Description

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

Detailed Description

The strategy of TACE + sorafenib is now being intensively investigated. It is a safe approach with significant beneficial effect on TTP in some studies, but the beneficial effect on OS remains uncertain. In the present study, we hypothesized that the GALNT14 genotype might play a role in this issue. Our pilot study indicated that GALNT14 "TT" genotype was associated with a favorable complete response rate in patients treated by TACE alone. This genotype was present in ~ 25% of Chinese population coming from Taiwan, Colorado (US), or Beijing (China), and in ~ 7% of Italian population. But it was present in ~ 50% of Japanese population. The lower percentage of a TACE - favorable genotype in Chinese and Italian population could explain the different results between Japanese and Chinese/Italian clinical trials. It is possible that in a population with higher percentage of TACE - favorable genotype (GALNT14 "TT"), the beneficial effect of sorafenib adjuvant treatment might not be detected. In this study, we proposed to examine the TACE + sorafenib effect in patients with GALNT14 "non-TT" genotype, a TACE - unfavorable genotype.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma

Keywords

SNPs

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

GALNT14 TT

Arm Type

Active Comparator

Arm Description

Arm Title

GALNT14 non-TT TACE alone

Arm Type

Active Comparator

Arm Description

Arm Title

GALNT14 non-TT TACE plus sorafenib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

sorafenib

Other Intervention Name(s)

Nexavar

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

TACE

Other Intervention Name(s)

Transcatheter arterial chemoembolization

Intervention Description

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

Primary Outcome Measure Information:

Title

Complete remission

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Time to partial (including complete) response

Time Frame

3 years

Title

Time-to-tumor-progression (TTP)

Time Frame

3 years

Title

Progression free survival (PFS).

Time Frame

3 years

Title

Overall survival (OS)

Time Frame

3 years

Title

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.

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Serum creatinine < 2 x ULN. Antiviral treatment for hepatitis B or C is allowed except for interferon. Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chau-Ting Yeh, MD/PhD

Organizational Affiliation

Chang Gung Memorial Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Chang Gung Memorial Hospital

City

Taoyuan

Country

Taiwan

12. IPD Sharing Statement

Citations:

PubMed Identifier

26871639

Citation

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.

Results Reference

result

PubMed Identifier

34982369

Citation

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.

Results Reference

derived

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

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