R-evolution trial

JRCT ID: jRCTs031190236

Registered date:03/03/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Hepatocellular carcinoma
• Date of first enrollment: 26/05/2020
• Target sample size: 30
• Study type: Interventional
• Intervention(s): Ramucirumab

Outcome(s)

• Primary Outcome: Progression free survival ratio after six months

Secondary Outcome

Overall survival (OS)
Progression free survival (PFS)
Time to progression (TTP)
Safety

Key inclusion & exclusion criteria

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

Include criteria

Patients who meet all of the following criteria will be included:
1)Patients must have been diagnosed with HCC by either of the following assessments:
a)Histological or cytological diagnosis of HCC
b)Radiographic image diagnosis of HCC by the typical findings 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)ECOG Performance Status (PS) of 0 or 1.
4)Patients with Child-Pugh class A
5)Patients must meet all of the following clinical testing criteria
a)White blood cell>=2000/uL
b)Neutrophil>=1000/uL
c)Hemoglobin>=9.0g/dL
d)Platelet>=75000/mm3
e)Total bilirubin<=1.5 times the upper limit of the facility reference
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) <=1.5 and activated partial thromboplastin time (APTT) <=1.5 times the upper limit of the facility reference
j)AFP>=400ng/mL
6)Patients must have measurable lesion with RECIST version 1.1.
7)Patients who received any of the following prior treatment as systemic chemotherapy and were discontinued for disease progression or intolerance
a) Lenvatinib
b) Combination chemotherapy of Atezolizumab and bevacizumab
c) Combination chemotherapy of Atezolizumab and bevacizumab followed by lenvatinib as a second line
8)Patients with no history of :
Systemic chemotherapy including sorafenib and regorafenib other than combination therapy of atezolizumab/ bevacizumab or lenvatinib.
Antineoplastic drug in development, antineoplastic chemotherapy, hormonal therapy, and immunotherapy within 28 days before enrollment.
9)Ages 20 and older (any gender).
10)Women of child bearing potential patients who agree to use 2 forms of effective contraception, where one form is highly effective (such as combined oral contraceptive), from study entry until at least 30 days after the last dose of study treatment and who have a negative pregnancy test within 7 days prior to enrollment. Women who are postmenopausal for at least 1 year (defined as cessation of menses for at least 1 year) or who are surgically sterilized do not require the test.
11)Patients who provide written informed consent based on free will after receiving sufficient explanation for the study.

Exclude criteria

Patients who meet any of the following criteria will be excluded from the study.
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 at least three years before enrollment and is considered to have not relapsed since then.
2)Patients on kidney dialysis.
3)Heart disease which falls into any of the following categories.
a)Heart failure of NYHA class 2 or higher.
b)Coronary artery disease with symptoms. History of myocardial infarction within 24 weeks prior to enrollment.
c)Arrhythmias that is uncontrolled by the treatment of antiarrhythmic drugs such as beta blocker and digoxin (CTCAE version 4.0 Grade 3 or higher).
d)Poorly controlled hypertension.
4)Severe and active infections (CTCAE version 4.0 Grade 3 orhigher).
5)History of HIV infection.
6)Portosystemic shunt with hepatic encephalopathy.
7)History of hepatic encephalopathy (Grade2 or higher).
8)Esophageal and gastric varices requiring treatment.
9)History of esophageal and gastric variceal bleeding.
10)Refractory ascites.
11)Patients with a history of gastrointestinal perforation or fistula within 6 months prior to enrollment.
12)Patients with a history of serious trauma or fracture within 6 months prior to enrollment.
13)Patients who have a serious or non-healing wound or ulcer within 28 days prior to the first dose of protocol therapy.
14)Detectable HBV-DNA without nucleic acid analog treatment.
15)Thromboembolism (cerebrovascular disorder including transient cerebral ischemic attack, deep vein thrombosis, pulmonary embolism etc.) within 6 months prior to enrollment.
16)Patients who use warfarin with therapeutic dose. Patients who have started treatment with or adjusted the dose of oral anticoagulants or low molecular weight heparin within 2 weeks of Ramucirumab administration.
17)Patients who are receiving chronic antiplatelet therapy, including dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted.
18)Patients who have a plan to undergo an operation during this study
19)Patients with the following medical history.
a)History of gastrointestinal bleeding which needs to be treated within 4 weeks prior to enrollment.
b)Medical history with invasive surgery within 4 weeks prior to enrollment.
c)History of homologous organ transplantation.
20)Pregnant or lactating woman; woman who plan or intend to become pregnant (In case of suspected pregnancy, pregnancy test should be conducted)
21)Possibility of allergic reaction to the study drug
22)Drug abuse. Health, psychological, social conditions that interfere with the participation of the study or evaluation of the results.
23)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: Ogasawara Sadahisa
• Source(s) of Monetary Support: Eli Lilly Japan K.K.