E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Carcinoma hepatocelular en pacientes que han progresado radiológicamente a un tratamiento anticancerígeno previo. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049010 |
E.1.2 | Term | Carcinoma hepatocellular |
|
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 assess the safety profile of BAY 73-4506 in patients with hepatocellular carcinoma (HCC). |
|
E.2.2 | Secondary objectives of the trial |
Efficacy, as assessed by Time to progression (TTP), Objective response rate (ORR) disease control rate (DCR), Overall survival (OS) and Pharmacokinetics |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
*Male or female patients aged equal or above18 years. *Histological or cytological confirmation of HCC or non-invasive diagnosis of HCC as per AASLD criteria. *BCLC stage Category A, B or C that cannot benefit from treatments of established efficacy with higher priority such as resection, liver transplantation, local ablation, chemoembolization or systemic sorafenib. *Liver function status Child-Pugh class A. *Failure to prior treatment with sorafenib (defined as radiological progression under sorafenib therapy) *Local or loco-regional therapy (eg, surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed ? 4 weeks before first dose of BAY 73-4506. *Recovery from any previous drug/procedure-related toxicity to CTC Grade 0 or 1 levels (except alopecia), or to baseline preceding the prior treatment. *ECOG PS of 0 or 1. *Adequate bone marrow, liver and renal function as assessed by the following laboratory tests conducted (Modified diet in renal disease) abbreviated formula *At least one naïve (not previously treated by locoregional therapy) uni-dimensional measurable lesion by computed tomography [CT] scan or magnetic resonance imaging [MRI] according to Response Evaluation Criteria (RECIST) and JNCI amendments regarding characterization of lesions in HCC *Life expectancy of at least 3 months. |
|
E.4 | Principal exclusion criteria |
*Prior treatment with BAY 73-4506. *Large esophageal varices at risk of bleeding that are not being treated with conventional medical intervention: beta blockers or endoscopic treatment. Assessment of esophageal varices should be performed by endoscopy within 6 months of study start, and within 12 months for patients in whom conventional medical intervention for known esophageal varices is already in place. *Prior systemic treatment with molecular targeted agents for HCC, except sorafenib. Prior chemotherapy treatment is allowed. *Past or concurrent history of neoplasm other than HCC, except for in situ carcinoma of the cervix uteri and/or basal cell epithelioma. Any cancer curatively treated > 5 years prior to study entry is permitted. *Known history or symptomatic metastatic brain or meningeal tumors (head CT or MRI at screening to confirm the absence of central nervous system [CNS] disease if patient has symptoms suggestive or consistent with CNS disease). *Major surgical procedure or significant traumatic injury within 28 days before start of study medication. *Pregnant or breast-feeding patients. *Congestive heart failure NYHA>= class 2 *Unstable angina (angina symptoms at rest, new ?onset angina ie, within the last 3 months) or myocardial infarction (MI) within the past 6 months before start of study medication. *Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted). *Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management). *Patients with phaeochromocytoma. *Ongoing infection > Grade 2 NCI-CTC version 3.0. *Persistent proteinuria of CTC Grade 3 or higher (> 3.5 g/24 hours, measured by urine protein/creatinine ratio on a random urine sample). *Clinically significant bleeding within 30 days before start of study medication. *Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study treatment. *Dehydration NCI-CTC version 3.0 Grade ? 1. *Unresolved toxicity higher than NCI-CTCAE (version 3.0) Grade 1 (excluding alopecia) attributed to any prior therapy/procedure. *Any illness or medical condition that is unstable or could jeopardize the safety of the patient and his/her compliance in the study. *Known history of human immunodeficiency virus (HIV) infection. *Patients with seizure disorder requiring medication. *History of organ allograft. *Non-healing wound, ulcer, or bone fracture. *Renal failure requiring hemo-or peritoneal dialysis. *Substance abuse, medical, psychological or social conditions that may interfere with the patient?s participation in the study or evaluation of the study results. *Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation. *Patients unable to swallow oral medications. *Interstitial lung disease with ongoing signs and symptoms at the time of screening. *Any malabsorption condition. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
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 | Yes |
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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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
|
The date of the final clean data base is defined as the end of the study |
|
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 |