Back to resultsTACE Combined With Methylcantharidimide Tablets in the Treatment of Large and Unresectable Hepatocellular Carcinoma
Primary Purpose
Hepatocellular Carcinoma
Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
methylcantharidimide tablets
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Transarterial Chemoembolization, Methylcantharidimide, Large and unresectable HCC
Eligibility Criteria
Inclusion Criteria:
- Age range from 18-75 years;
- KPS≥70;
- The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL);
- Simultaneously staged as BCLC A or BCLC B based on Barcelona Clinic Liver Cancer staging system;
- Patients must have at least one tumor lesion that can be accurately measured;
- Solitary tumor with diameter ≥10cm, or multiple tumors, diameter of the largest was more than 7cm;
- Diagnosed as unresectable with consensus by the panel of liver surgery experts,
- Re commanded treated by TACE with consensus by the panel of liver multi-disciplinary treatment (MDT);
- No past history of TACE, chemotherapy or molecule-targeted treatment;
- No Cirrhosis or cirrhotic status of Child-Pugh class A only;
- No liver protection therapy in 2 weeks before enrolled, and meet the following laboratory parameters:(a) Platelet count ≥ 75,000/μL; (b)Hemoglobin ≥ 8.5 g/dL;(c) Total bilirubin ≤ 30mmol/L;(d) Serum albumin ≥ 32 g/L;(e) Glutamic pyruvic transaminase (ALT) and glutamic oxalacetic transaminase (AST) ≤ 6 x upper limit of normal;(f) Serum creatinine≤ 1.5 x upper limit of normal;(g) international normalized ratio（INR）> 2.3 or prothrombin time (PT)/activated partial thromboplastin time (APTT) within normal limits; (h) Absolute neutrophil count (ANC) >1,500/mm3;
- Ability to understand the protocol and to agree to sign a written informed consent document.
Exclusion Criteria:
- Factors that affect oral administration, such as dysphagia, chronic diarrhea and intestinal obstruction;
- Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry;
- Known of serious heart disease which can nor endure the treatment such as cardiac ventricular arrhythmias requiring anti-arrhythmic therapy;
- Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy;
- Known history of HIV;
- History of organ allograft;
- Known or suspected allergy to the investigational agents or any agent given in association with this trial;
- Evidence of bleeding diathesis;
- Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug;
- Serious non-healing wound, ulcer, or bone fracture;
- Known central nervous system tumors including metastatic brain disease;
- Poor compliance that can not comply with the course of treatment and follow up;
- Factors that the researchers consider it not appropriate to be included
Sites / Locations
- Suzhou Municipal Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
TACE plus methylcantharidimide tablets
Arm Description
Methylcantharidimide tablets( 75mg po tid) is administered before first TACE 3 days and taken continuously after TACE treatment. Every 6 weeks is a cycle.
Outcomes
Primary Outcome Measures
Disease control rate (DCR)
DCR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), or stable disease (SD). CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference the baseline sum of the diameters of target lesions. SD was when a case does not qualify for either PR or progressive disease (PD) and was new non-target lesions. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions.
Secondary Outcome Measures
Time to progression (TTP)
TTP was defined as the time from the date of treatment to the date of first documentation of disease progression based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions.
Overall Survival (OS)
From the date of treatment until the date of death from any cause
Health Related Quality of Life (HRQoL)
HRQoL assessed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) .The EORTC QLQ-C30 included 30 questions comprising 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social) and 9 symptom scales (fatigue, pain, nausea/vomiting, dyspnoea, appetite loss, insomnia, constipation, diarrhea and financial difficulties) and a single global health and quality of life status score. Most questions used a 4-point scale (1=Not at all to 4=Very much); 2 questions used a 7-point scale (1= Very poor to 7=Excellent). All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem.
clinical symptoms
A questionnaire about the clinical symptoms, appetite，pain and sleep.
Adverse Events
Postoperative adverse events were graded based on CTCAE v4.03
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03996681
Brief Title
TACE Combined With Methylcantharidimide Tablets in the Treatment of Large and Unresectable Hepatocellular Carcinoma
Official Title
A Prospective Clinical Trial of TACE Combined With Methylcantharidimide Tablets in the Treatment of Large and Unresectable Hepatocellular Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Unknown status
Study Start Date
July 20, 2019 (Anticipated)
Primary Completion Date
July 20, 2020 (Anticipated)
Study Completion Date
February 1, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Suzhou Municipal Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with methylcantharidimide tablets in the treatment of patients with large and unresectable hepatocellular carcinoma.
Detailed Description
Most guidelines recommend transarterial chemoembolization (TACE), as the standard of care for unresectable hepatocellular carcinoma (HCC ) at Barcelona Clinic Liver Cancer (BCLC) stage A-B. While a number of studies demonstrate poor effect of TACE for patients with large hepatocellular carcinoma. The efficacy of TACE on large (≥ 10 cm) stage A-B HCC is far from satisfactory. The median overall survival was only 6.5-9.1 months. Methylcantharidimide is a single molecule drug used for the treatment of primary liver cancer.
Thus, the investigators carried out this prospective trial to demonstrate the efficacy and safety of TACE combined with methylcantharidimide tablets in patients with large and unresectable hepatocellular carcinoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Transarterial Chemoembolization, Methylcantharidimide, Large and unresectable HCC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
TACE plus methylcantharidimide tablets
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
TACE plus methylcantharidimide tablets
Arm Type
Experimental
Arm Description
Methylcantharidimide tablets( 75mg po tid) is administered before first TACE 3 days and taken continuously after TACE treatment. Every 6 weeks is a cycle.
Intervention Type
Drug
Intervention Name(s)
methylcantharidimide tablets
Other Intervention Name(s)
GANYU
Intervention Description
Drug: methylcantharidimide tablets
Methylcantharidimide is a single molecule drug used for the treatment of primary liver cancer.
Procedure: TACE
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
Disease control rate (DCR)
Description
DCR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), or stable disease (SD). CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference the baseline sum of the diameters of target lesions. SD was when a case does not qualify for either PR or progressive disease (PD) and was new non-target lesions. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Time to progression (TTP)
Description
TTP was defined as the time from the date of treatment to the date of first documentation of disease progression based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions.
Time Frame
18 months
Title
Overall Survival (OS)
Description
From the date of treatment until the date of death from any cause
Time Frame
18 months
Title
Health Related Quality of Life (HRQoL)
Description
HRQoL assessed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) .The EORTC QLQ-C30 included 30 questions comprising 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social) and 9 symptom scales (fatigue, pain, nausea/vomiting, dyspnoea, appetite loss, insomnia, constipation, diarrhea and financial difficulties) and a single global health and quality of life status score. Most questions used a 4-point scale (1=Not at all to 4=Very much); 2 questions used a 7-point scale (1= Very poor to 7=Excellent). All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem.
Time Frame
18 months
Title
clinical symptoms
Description
A questionnaire about the clinical symptoms, appetite，pain and sleep.
Time Frame
18 months
Title
Adverse Events
Description
Postoperative adverse events were graded based on CTCAE v4.03
Time Frame
18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age range from 18-75 years;
KPS≥70;
The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL);
Simultaneously staged as BCLC A or BCLC B based on Barcelona Clinic Liver Cancer staging system;
Patients must have at least one tumor lesion that can be accurately measured;
Solitary tumor with diameter ≥10cm, or multiple tumors, diameter of the largest was more than 7cm;
Diagnosed as unresectable with consensus by the panel of liver surgery experts,
Re commanded treated by TACE with consensus by the panel of liver multi-disciplinary treatment (MDT);
No past history of TACE, chemotherapy or molecule-targeted treatment;
No Cirrhosis or cirrhotic status of Child-Pugh class A only;
No liver protection therapy in 2 weeks before enrolled, and meet the following laboratory parameters:(a) Platelet count ≥ 75,000/μL; (b)Hemoglobin ≥ 8.5 g/dL;(c) Total bilirubin ≤ 30mmol/L;(d) Serum albumin ≥ 32 g/L;(e) Glutamic pyruvic transaminase (ALT) and glutamic oxalacetic transaminase (AST) ≤ 6 x upper limit of normal;(f) Serum creatinine≤ 1.5 x upper limit of normal;(g) international normalized ratio（INR）> 2.3 or prothrombin time (PT)/activated partial thromboplastin time (APTT) within normal limits; (h) Absolute neutrophil count (ANC) >1,500/mm3;
Ability to understand the protocol and to agree to sign a written informed consent document.
Exclusion Criteria:
Factors that affect oral administration, such as dysphagia, chronic diarrhea and intestinal obstruction;
Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry;
Known of serious heart disease which can nor endure the treatment such as cardiac ventricular arrhythmias requiring anti-arrhythmic therapy;
Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy;
Known history of HIV;
History of organ allograft;
Known or suspected allergy to the investigational agents or any agent given in association with this trial;
Evidence of bleeding diathesis;
Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug;
Serious non-healing wound, ulcer, or bone fracture;
Known central nervous system tumors including metastatic brain disease;
Poor compliance that can not comply with the course of treatment and follow up;
Factors that the researchers consider it not appropriate to be included
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lei Chen, MD
Phone
+86-13771775313
Email
leichensz@sina.com
First Name & Middle Initial & Last Name or Official Title & Degree
Mo Zhou
Phone
+86 0512-62362596
Email
szslyyec@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lei Chen, MD
Organizational Affiliation
Suzhou Municipal Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Suzhou Municipal Hospital
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215008
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mo Zhou, MD
Phone
+86 0512-62362596
Email
szslyyec@163.com
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
all individual participant data (IPD) that underlie results in a publication
IPD Sharing Time Frame
starting 6 months after publication
IPD Sharing Access Criteria
Case Report Form (CRF)
Citations:
PubMed Identifier
29061175
Citation
He MK, Le Y, Li QJ, Yu ZS, Li SH, Wei W, Guo RP, Shi M. Hepatic artery infusion chemotherapy using mFOLFOX versus transarterial chemoembolization for massive unresectable hepatocellular carcinoma: a prospective non-randomized study. Chin J Cancer. 2017 Oct 23;36(1):83. doi: 10.1186/s40880-017-0251-2.
Results Reference
background
PubMed Identifier
25682389
Citation
Xue T, Le F, Chen R, Xie X, Zhang L, Ge N, Chen Y, Wang Y, Zhang B, Ye S, Ren Z. Transarterial chemoembolization for huge hepatocellular carcinoma with diameter over ten centimeters: a large cohort study. Med Oncol. 2015 Mar;32(3):64. doi: 10.1007/s12032-015-0504-3. Epub 2015 Feb 15.
Results Reference
background
PubMed Identifier
16393290
Citation
Huang YH, Wu JC, Chen SC, Chen CH, Chiang JH, Huo TI, Lee PC, Chang FY, Lee SD. Survival benefit of transcatheter arterial chemoembolization in patients with hepatocellular carcinoma larger than 10 cm in diameter. Aliment Pharmacol Ther. 2006 Jan 1;23(1):129-35. doi: 10.1111/j.1365-2036.2006.02704.x.
Results Reference
background
PubMed Identifier
10694648
Citation
Poon RT, Ngan H, Lo CM, Liu CL, Fan ST, Wong J. Transarterial chemoembolization for inoperable hepatocellular carcinoma and postresection intrahepatic recurrence. J Surg Oncol. 2000 Feb;73(2):109-14. doi: 10.1002/(sici)1096-9098(200002)73:23.0.co;2-j.
Results Reference
background
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TACE Combined With Methylcantharidimide Tablets in the Treatment of Large and Unresectable Hepatocellular Carcinoma
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