REGAIN trial

JRCT ID: jRCTs031190103

Registered date:25/09/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Hepatocellular carcinoma
• Date of first enrollment: 14/01/2020
• Target sample size: 192
• Study type: Interventional
• Intervention(s): Regorafenib

Outcome(s)

• Primary Outcome: Time to progression (modified RECIST and RECIST version 1.1)

Secondary Outcome

Secondary outcomes of efficacy
Overall survival
Progression free survival (modified RECIST and RECIST version 1.1)
Secondary outcomes of safety
Frequency of adverse events
Rate of discontinuation by adverse events

Key inclusion & exclusion criteria

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

Include criteria

Patients must meet all of the following criteria to be included in this study:
1)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.
2) 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).
3)EOCG Performance Status(PS)of 0 or 1.
4)Liver function status is Child-Pugh class A.
a)HCC is classified into Child-Pugh class A to C,employing the added score of 5 clinical parameters.
b)Child-Pugh classification: A (5-6), B (7-9), and C(10-15)
5)Patients must meet all of the following criteria of clinical lab tests.
a)White blood cell>=2000/uL
b)Neutrophil>=1000/uL
c)Hemoglobin>=8.5g/dl
d)Platelet>=50000/mm3
e)Total bilirubin<=3.0mg/dl
f)AST, ALT<=5 times the upper limit of the facility reference
g)Serum Creatinine<=1.5 times the upper limit of the facility reference
h)Serum albumin>=2.8g/dl
i)Prothrombin time(PT-INR)<=2.3
6)Patients must have measurable lesion with RECIST version 1.1 and modified RECIST(mRECIST).
7)Ages 20 and older(any gender).
8)Patients with written consent after receiving sufficient explanation for this study. The consent is based on free will.
9)Men or Women who can agree to use adequate contraception.
10)The last treatment is one of the following.
[Arm A]The last treatment was sorafenib, which met all of the following:
Patients who have failed prior treatment with sorafenib(defined as radiological progression).
Patients who could be administered with sorafenib at a dose of 200 mg daily or 400 mg every other day for more than 28 days, but they couldn't meet an inclusion criterion of RESORCE study such as "Patients who can be administered with sorefenib for not less than 20 days at a minimum daily dose of 400mg within the last 28 days prior to withdrawal".
Patients whose dose control during sorafenib treatment are clear.
[Arm B]The last treatment was lenvatinib, which met all of the following:
Patients whose previous treatment was lenvatinib and no treatment history of sorafenib.
Patients who received prior treatment with lenvatinib and finished it due to disease progression or intolerance of the drug.
[Arm C]The last treatment was atezolizumab plus bevacizumab, which met all of the following:
Patients whose previous treatment was atezolizumab plus bevacizumab and no treatment history of sorafenib.
Patients who received prior treatment with atezolizumab+bevacizumab and finished them due to disease progression or intolerance of the drugs.
11)More than two weeks after the last treatment with sorafenib or lenvatinib.

Exclude criteria

Patients who fall under any of the following criteria, will be excluded from the study.
1)Patients who have been administered with regorafenib for advanced HCC
2)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 two years prior to the study and is considered to have not relapsed since then.
3)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.
4)Severe and active infections (CTCAE version 4.0 Grade 3 or higher).
5)Urine protein (CTCAE version 4.0 Grade3 or higher) other than the following cases.24-hour urine test (urine protein/urine creatinine ratio can be substituted as 24-hour urine test) is less than 3.5g.
6)History of HIV infection.
7)Detectable HBV-DNA without nucleic acid analog treatment.
8)Patients on kidney dialysis
9)Intracranial tumor (including intracranial metastasis).
10)History of hepatic encephalopathy (Grade2 or higher).
11)Esophageal and gastric varices requiring treatment
12)Refractory ascites
13)Thromboembolism (cerebrovascular disorder including transient cerebral ischemic attack, deep vein thrombosis, pulmonary embolism etc.) within 6 months before the start of the study
14)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 providing consent
d)Prior treatment for HCC with local therapy (radiofrequency ablation, ethanol injection, microwave ablation) within 4 weeks prior to providing consent
e)Prior treatment for HCC with transvascular intervention therapy (transarterial chemoembolization etc.) within 4 weeks prior to providing consent
f)Medical history with invasive surgery within 12 weeks prior to providing consent
g)History of homologous organ transplantation
h)History of bone marrow transplantation / hematopoietic stem cell transplantation
15)Gastrointestinal disorders which may affect drug absorption and pharmacokinetics
16)Use of drugs which may affect drug absorption and pharmacokinetics
17)Pregnant or lactating woman; woman of child bearing age unless using effective contraception (In case of suspected pregnancy, pregnancy test should be conducted)
18)Possibility of allergic reaction to the study drug
19)Drug abuse. Health, psychological, social conditions that interfere with the participation of the study or evaluation of the results
20)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
• Secondary Sponsor: Ogasawara Sadahisa
• Source(s) of Monetary Support: Bayer Yakuhin, Ltd