E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Hepatocellular Carcinoma |
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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 | 10049010 |
E.1.2 | Term | Carcinoma hepatocellular |
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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 |
To demonstrate that OS on sunitinib is superior or equivalent to OS on sorafenib in patients with advanced hepatocellular carcinoma |
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E.2.2 | Secondary objectives of the trial |
• To compare PFS and TTP between both treatment arms • To evaluate the safety and tolerability of sunitinib in this patient population • To compare patients’ health status between both treatment arms. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically-confirmed diagnosis of hepatocellular carcinoma that is locally advanced or metastatic (histological diagnosis obtained from a prior tumor biopsy specimen is acceptable). 2. Measurable disease according to RECIST. At least one target lesion should not have previously received any local therapy, such as surgery, radiation therapy, hepatic arterial embolization, TACE, hepatic arterial infusion, radio-frequency ablation, percutaneous ethanol injection or cryoablation, unless it has subsequently progressed according to RECIST. 3. Resolution of all acute toxic effects of any prior local treatment to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 grade ≤1. 4. Child-Pugh class A (for the determination of the Child-Pugh class, use the table reported in Appendix 5 of the protocol). 5. Eighteen years of age or older. 6. ECOG performance status 0 or 1. 7. Required baseline laboratory data within the following parameters: • Neutrophils ≥ 1,500/µL • Platelets ≥ 75,000/µL • Hemoglobin ≥ 9.0 g/dL • Serum aspartate aminotransferase (AST; serum glutamate-oxalate transferase [SGOT]) and serum alanine aminotransferase (ALT; serum glutamate-pyruvate transferase [SGPT]) ≤ 5 x ULN • Serum creatinine ≤ 1.5 x ULN • INR <1.7 or prothrombin time (PT) < 4 seconds above ULN • Serum albumin > 3.5 g/dL (* ≥ 2.8 g/dL) • Total bilirubin < 2 mg/dL (* ≤ 3 mg/dL) * ONLY ONE of these 2 last criteria may have a score of 2 according to the Child-Pugh scoring system. 8. Candidate for treatment with sorafenib. Safety precautions as detailed in sorafenib package insert or equivalent documentation but not stated in study entry criteria must be ensured by the investigator prior to randomization (e.g. sorafenib is contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of NEXAVAR®). 9. Signed and dated informed consent indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment. 10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including completion of patient-reported outcome (PRO) questionnaires. |
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E.4 | Principal exclusion criteria |
1. Prior systemic treatment for HCC, including prior treatment with sunitinib, or sorafenib, or another investigational agent. 2. Any prior local therapy (such as surgery, radiation therapy, hepatic arterial embolization, TACE, hepatic arterial infusion, radiofrequency ablation, percutaneous ethanol injection or cryoablation) within 4 weeks of study entry. 3. Prior history of liver transplant. 4. Presence of clinically relevant ascites (e.g., requiring therapeutic paracentesis or that can be classified as Child-Pugh score ≥ 2). 5. NCI CTCAE grade ≥ 3 hemorrhage within 4 weeks of starting study treatment, or documented variceal hemorrhage of any grade within 12 months of study entry (as documented by endoscopy). 6. Presence of esophageal varices at risk of bleeding and/or serious or non-healing wound/ulcer (as documented by endoscopy). 7. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of study entry. 8. Any of the following within the 12 months prior to study drug administration: severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, including transient ischemic attack, or pulmonary embolism. 9. Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma of the cervix uteri that has been adequately treated without evidence of recurrent disease for 12 months. 10. History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease. 11. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥ 2, atrial fibrillation of any grade, or prolongation of the QTc interval to > 450 msec for males or > 470 msec for females. 12. Hypertension that cannot be controlled by medications (blood pressure >150/100 mm Hg despite optimal medical therapy). 13. Treatment with potent CYP3A4 inhibitor within 7 days of study entry or with potent CYP3A4 inducer within 12 days of study entry. 14. Concomitant treatment with botanical formulation having an approved indication for cancer treatment, such as “Xiao Chai Hu Tang”, “Kanglaite”, etc. 15. Ongoing treatment with therapeutic levels of coumarin derivatives or oral anti-vitamin K agents. 16. Inability to swallow oral medications, or presence of active inflammatory bowel disease, partial or complete bowel obstruction or chronic diarrhea. 17. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. 18. Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within the 7 days prior to study enrollment. 19. Fertile patients unwilling or unable to use adequate contraception, as defined in Life Style Guidelines, Section 4.4, to prevent pregnancy during the study. 20. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 71 |
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
|
Please refer to section 13 of the protocol |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |