E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
To evaluate the clinical benefit of sorafenib 400 mg twice daily and erlotibib 150 mg once a day in subjects with unresectable advanced or metastatic Child-Pugh A HCC. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019828 |
E.1.2 | Term | Hepatocellular carcinoma non-resectable |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019829 |
E.1.2 | Term | Hepatocellular carcinoma recurrent |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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E.2.2 | Secondary objectives of the trial |
Time to radiographic Tumor Progression (TTP)
Disease Control Rate (DCR)
Safety
Health Related Quality of Life (HRQoL) and utility values as measured by EQ-5D |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with histological or cytologically documented HCC or clinical diagnosis by AASLD criteria in cirrhotic subjects is required. For subjects without cirrhosis histological confirmation is necessary.
• Patients must have at least one tumor lesions that meets both of the following criteria: - Lesion can be accurately measured in at least one dimension according to RECIST - Lesion has not been previously treated with local therapy (such as surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation
• Patients who have received local therapy are eligible. Local theapy must be completed at least 4 weeks prior to the baseline scan. Previously treated lesions will not be selected as target lesions.
• Patients with an ECOG PS of 0 or 1.
• Cirrhotic status of Child-Pugh Class A.
• Following Laboratory Parameters (as assessed by Central Laboratory): - Platelet count ≥ 60 x 109/L - Hemoglobin ≥ to 8.5 g/dl - Total Bilirubin ≤ 2.8 mg/dl - ALT and AST ≤ 5 x ULN - Serum Creatinine ≤ 1.5 x ULN - PT international normalized ration (INR) ≤ 2.3 or PT ≤ 6 seconds above control - Patients who are being therapeutically anticoagulated with an agent such as wafarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.
• Patients must provide written informed consent prior to any study procedures being performed
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E.4 | Principal exclusion criteria |
• Renal failure requiring hemo- or peritoneal dialysis
• Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) – related illness or serious acute or chronic illness.
• Abnormalities of the cornea based on history (e.g. dry eye syndrome, Sogren’s syndrome) including congenital abnormality (e.g. Fuch’s dystrophy), abnormal slit-lamp examination using a vital dye (e.g. fluorescein, Bengal-Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test).
• Child-Pugh class B or C
• Previous treatment with yttrium- 90 spheres
• Clinically significant peripheral vascular disease
• History of cardiac disease: congestive heart failure > New York Heart Association (NYHA) class 2; active coronary artery disease (CAD); cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin), or uncontrolled hypertension. Myocardial infarction more than 6 months prior to study entry is permitted. (See Appendix 10.7)
• History of interstitial lung disease (ILD)
• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry
• Active clinically serious infections (> grade 2 National Cancer Institute [NCI]-Common Terminology Criteria for Adverse Events [CTCAE] version 3.0), except HBV/HCV infections
• Uncontrolled ascites (defined as not easily controlled with diuretic treatment)
• Pregnant or breast-feeding patients.
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Survival measured via patient phone contacts after treatment is complete |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 14 |