Dose re-escalation study of sorafenib in patients with HCC

JRCT ID: jRCTs031180429

Registered date:26/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Hepatocellular carcinoma
• Date of first enrollment: 08/07/2014
• Target sample size: 250
• Study type: Interventional
• Intervention(s): sorafneib

Outcome(s)

• Primary Outcome: Time to progression after randomization

Secondary Outcome

Overall survival
Overall survival after randomization
Time to progression
Drug concentration of sorafenib
Safety

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Age: 20 years or more
2) Patients with written consent after receiving sufficient explanation for this study. The consent is based on free will.
3) Patients must have been diagnosed with HCC base on either of the following assessments:
a) Histological or cytological diagnosis of HCC
b) Radiographic image diagnosis of HCC by the typical findings of a hypervascular tumor on dynamic CT, CTHA/CTAP, dymamic MRI.
4) Patients must meet all of the following criteria on treatment of HCC:
a) Not applicable for surgical resection.
b) Not applicable for any local therapies (radio frequency ablation, percutaneous ethanol injection, microwave ablation).
c) Not applicable for transarterial chemoembolization (TACE). imum target lesion diameter>=10mm
5) Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1
6) Child Pugh score <= 7
7) Life expectation of 12 weeks or over
8) Capablity of complying with procedures and visits as specified by the protocol
9) Patients must meet all of the following criteria of clinical lab tests.
a) Hemoglobin>=8.5g/dl
b) White blood cell>=2000/mm3
c) Platelat>=50000/mm3 d) Total bilirubin<=3.0mg/dL
e) AST, ALT<=5 times the upper limit of the facility reference
f) Serum albumin>=2.5g/dL
g) Serum Creatinine<=1.5 times the upper limit of the facility reference
h) Serum Amylase<=2 times the upper limit of the facility reference
i) Prothrombin time(PT-INR) <=2.3

Exclude criteria

1) Patients with a history of malignant tumors except for the following cases.
a) Early stage cancers with a low risk of relapse after appropriate radical treatment such as intraepithelial cervical cancer, basal cell carcinoma, superficial bladder tumor (Ta, Tis and T1) and early gastric cancer.
b) Malignant tumors that have been given radical treatment for more than three years prior to the study and is considered to have not relapsed since then.
2) Heart disease which falls under any of the following.
a) Heart failure of NYHA class 3 or higher.
b) Coronary artery disease with symptoms. History of myocardial infarction within 24 weeks prior to enrollment.
c) Arrhythmias requiring control with antiarrhythmic drugs such as beta blocker and digoxin (CTCAE version 4.0 Grade 3 or higher).
d) Poor control hypertension.
3) Severe and active infections (CTCAE version 4.0 Grade 3 or higher).
4) History of HIV infection
5) Detectable HBV-DNA without nucleic acid analog treatment
6) Patients on kidney dialysis
7) Intracranial tumor, including Metastatic Brain Tumor
8) History of hepatic encephalopathy(Grade2 or higher)
9) Esophageal and gastric varices requiring treatment
10) Refractory ascites
11) Thromboembolism (cerebrovascular disorder including transient cerebral ischemic attack, deep vein thrombosis, pulmonary embolism etc.) within 6 months before the start of study
12) Patients with the following medical history, but not with history of palliative radiation exposure to bone metastasis
a) Use of CYP3A4 inducer (rifampicin etc.)
b) Use of Warfarin
c) History of bleeding which needs to be treated within 4 weeks prior to the start of study
d) Local therapy for HCC, such as radio frequency ablation, percutaneous ethanol injection or microwave ablation within 4 weeks prior to the start of study
e) History of Percutaneous therapy (TACE etc.)
f) History of invasive surgery within 12 weeks prior to the start of study
g) History of homologous organ transplantation
h) History of bone marrow transplantation or hematopoietic stem cell transplantation
13) Gastrointestinal disorders which may affect drug absorption and pharmacokinetics
14) Use of drugs which may affect drug absorption and pharmacokinetics
15) Pregnant or lactating woman; woman of child bearing age unless using effective contraception (In case of susupected pregnancy, pregnanvy test should be conducted)
16) Possibility of allergic reaction to the study drug
17) Drug abuse. Health, psychological or social conditions that interfere with the participation of the study or evaluation of the results
18) Any condition that in the opinion of the investigators could Impair the patient' s safety or make the study difficult to comply with the protocol by participating in the study

Related Information

• Primary Sponsor: Kato Naoya
• Source(s) of Monetary Support: Bayer Yakuhin.Ltd.
• Secondary ID(s): UMIN000014566