A Clinical study to determine whether tivantinib is safe and effective in the treatment of liver cancer.
- Conditions
- MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC)MedDRA version: 19.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-003308-10-DE
- Lead Sponsor
- Daiichi Sankyo , Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 303
1. Written informed consent granted prior to initiation of any study-specific screening procedures
2. 18 years of age or older
3. Histologically confirmed HCC that is inoperable (where surgery is not indicated due to disease extension, co-morbidities, or other technical reasons) and not eligible for local therapy
4. MET Diagnostic-High tissue reported by the central authorized laboratory using archival or recent biopsy tumor samples (see lab manual and Section 6.1 of protocol for tissue preparation details).
5. Received at least 4 weeks of one prior sorafenib containing systemic therapy and then experienced documented radiographic disease progression; or inability to tolerate prior therapy received for at least a minimum period of time. For the purpose of this study, intolerance to sorafenib is determined as follows:
•The subject must have tried to take sorafenib for a period of at least 28 days (even intermittently)
•The subject must have tried to dose reduce sorafenib at =50% of the full dose for a period of at least 14 days (even intermittently) and still have a documented Grade =2 toxicity
•A period of even less than 14 days on sorafenib is acceptable in case of:
i. Uncontrolled Grade 3 - 4 arterial hypertension
ii. Pancreatitis, cardiac event, encephalopathy related to sorafenib
iii. = Grade 2 Hand-foot syndrome triggered even at 50% of the sorafenib dose
6. Discontinued prior systemic treatment or any investigational drug for at least 2 weeks (14 days) or for at least 3 weeks for IV anti-cancer drugs, prior to the study randomization
7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) = 1 (Appendix 17.2)
8. Local or loco-regional therapy (i.e., surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed = 4 weeks prior to randomization and are allowed.
9. Measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Tumor lesions previously treated with local therapy should demonstrate clear dimensional increase by radiographic assessment in order to be selected as target lesion(s) at baseline. Baseline radiographic assessment needs to be done within 21 days prior to randomization.
10. Adequate bone marrow, liver, and renal functions at Screening Visit, defined as: platelet count = 60 × 109/L; hemoglobin = 9.0 g/dL; absolute neutrophil count (ANC) = 1.5 × 109/L; total bilirubin = 2 mg/dL; Alanine transaminase (ALT) and aspartate aminotransferase (AST) = 5 × upper limit of normal (ULN); serum creatinine = 1.5 × ULN; albumin = 2.8 g/dL; international normalized ratio (INR) 0.8 to ULN or = 3 for subjects receiving anticoagulant such as coumadin or heparin. Subjects who are therapeutically anticoagulated are allowed to participate provided that prior to anticoagulant therapy no evidence of underlying defect in coagulation exists
11. Women of childbearing potential must have a negative serum pregnancy test performed within 14 days prior to the randomization (where demanded by local regulations, test may be required within 72 hours prior to randomization)
12. Male and female subjects of child-bearing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last study drug dose received
13. Life expectancy of at least 12 weeks
Are the trial subjects under
1. >1 prior systemic regimen (prior MET inhibitors/antibodies are not allowed; experimental systemic therapy for inoperable HCC given before or after sorafenib counts as separate regimen and is not allowed)
2. Child-Pugh B-C cirrhotic status based on clinical findings and laboratory results during screening period (see Appendix 17.4 for Child-Pugh Classification and interpretation of ascites at physical examination and Prothrombin Time (PT)/ International Normalized Ratio (INR))
3. Previous or concurrent cancer that is distinct from HCC in primary site or histology, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, and superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 3 years prior to enrollment is permitted.
4. History of congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification (see Appendix 17.5) within 6 months prior to study entry; active coronary artery disease (CAD); clinically significant bradycardia or other uncontrolled, cardiac arrhythmia defined as = Grade 3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, or uncontrolled hypertension; myocardial infarction occurring within 6 months prior to study entry (myocardial infarction occurring > 6 months prior to study entry is permitted)
5. Active clinically serious infections defined as = Grade 3 according to NCI CTCAE, version 4.03
6. Any medical, psychological, or social conditions, particularly if unstable, including substance abuse, that may, in the opinion of the Investigator, interfere with the subject’s safety or participation in the study, protocol compliance, or evaluation of the study results
7. Known human immunodeficiency virus (HIV) infection
8. Blood or albumin transfusion within 5 days prior to the blood draw being used to confirm eligibility
9. Concomitant interferon therapy or therapies for active Hepatitis C Virus (HCV) infection
10. Pregnancy or breast-feeding
11. History of liver transplant
12. Inability to swallow oral medications
13. Clinically significant gastrointestinal bleeding occurring = 4 weeks prior to randomization
14. Pleural effusion or clinically evident (visible or palpable) ascites
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method