A proof-of-concept Phase II study to evaluate efficacy, safety and pharmacokinetics of 4SC-201 and the treatment combination of Sorafenib plus 4SC-201 in patients with hepatocellular carcinoma exhibiting progressive disease under Sorafenib treatment

• Conditions: Hepatocellular carcinoma non-resectable; MedDRA version: 14.1Level: PTClassification code 10019695Term: Hepatic neoplasmSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2009-010760-42-IT
• Lead Sponsor: 4SC AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03-01
• Last Update Posted: 11 April 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 74

Inclusion Criteria

1. Male or female P 18 years; 2. Written informed consent obtained prior to any trial specific procedure; 3. Advanced stage hepatocellular carcinoma, BCLC class B (intermediate stage, performance status 0, multinodular HCC) or C (advanced stage, performance status-ECOG 1-2, invasive tumor pattern (vascular invasion/extra hepatic spread)), with either histological proven HCC or clinical diagnosis of HCC by AASLD criteria (HCC defined in cirrhotic patients by one imaging technique (CT, MRI or second generation contrast ultrasound) showing a nodule of > 2 cm with contrast uptake in the arterial phase and washout in venous or late phases or two imaging techniques showing this radiological behavior for nodules of 1 to 2 cm in diameter), exhibiting PD under Sorafenib treatment. For patients without cirrhosis, histological confirmation of HCC is mandatory; 4. Exhibiting PD under Sorafenib treatment, as detected by at least one CT/MRI scan within 4 weeks prior to study inclusion. Progressive disease will be confirmed by an independent radiological review; 5. Child-Pugh class A and B. Only patients with Child-Pugh index class B of not more than 7 will be included. Patients with more than slight ascites or hepatic encephalopathy > Grade 1 are excluded (see exclusion criteria); 6. ECOG performance status 0, 1 or 2 (refer to Appendix C for definitions of ECOG grades); 7. Life expectancy of 12 weeks or more; 8. Precedent first-line treatment with Sorafenib minimum dosing of 400 mg per day for at least 8 weeks. Treatment interruptions for any reason must not be more in the sum than 14 days within this 8 week period. Patients have stopped Sorafenib therapy not more than 10 weeks prior to treatment start, but at least 2 weeks prior to treatment start;; 9. Adequate hematological parameters, as demonstrated by: • Hemoglobin P 9.0 g/dl (SI units: 5.6 mmol/l); • White Blood Cells (WBCs) P 3.0 x 109/l; • Absolute neutrophil count P1,500/mm3; • Platelets P 75 x 109/l; • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) T 5 times upper limit of normal range (ULNR); • Bilirubin T 3 mg/dl; • Serum creatinine T 1.5 mg/dl (SI units: 132 Umol/l); • Prothrombin Time (PT) International Normalized Ratio (INR) T 2.3; • Serum potassium, magnesium and calcium within normal range; 10. Safe contraception in females of childbearing potential during the entire study using an established treatment with hormonal contraceptives for at least 2 months prior to start of screening; 11. For females of child bearing potential (without using hormonal contraceptives for at least 2 months prior to start of screening) a double contraception method is requested during the entire study meeting the criteria for an effective method of birth control. That means at least two effective birth control methods such as condoms, diaphragms or intra-uterine devices must be used; 12. Male patients with partners of child bearing potential are requested to use barrier contraception in addition to having their partner use another method of contraception during the trial and for 3 months after the last dose. Male patients will also be advised to abstain from sexual intercourse with pregnant or lactating women, or to use condoms; 13. Completes a period of at least 30 days since ending investigational device or drug trials and have recovered from treatment-related toxicities; 14. Able to comply with all the requirements of the protoco

Exclusion Criteria

1. Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis and T1). Any cancer curatively treated > 3 years prior to entry is permitted; 2. Renal failure requiring hemo- or peritoneal dialysis; 3. Known central nervous system (CNS) tumors including symptomatic brain metastasis; 4. Patients with no adequate treatment for gastrointestinal bleeding and esophagus varices within 14 days prior to study entry. IMP administration is scheduled to start within 14 days after adequate treatment. 5. Child-Pugh index class B in combination with more than slight ascites or hepatic encephalopathy > Grade I (see Child-Pugh index, Appendix D); 6. History and current cardiovascular complications, including unstable angina pectoris, uncontrolled hypertension, congestive heart failure (NYHA Class III or IV) related to primary cardiac disease, a condition requiring anti arrhythmic therapy, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the trial entry; A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds (ms)); A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome); 7. The use of concomitant medications that prolong the QT/QTc interval (see Appendix B) and treatment with cytokine growth factors; 8. Current evidence of any severe internal, psychiatric or neurologic disease; 9. Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies; 10. Pregnant or breastfeeding women; 11. Sorafenib intolerance; 12. History of allergic reactions attributed to compounds of similar chemical or biological composition to the study drug; 13. Active alcohol and/or drug abuse; 14. Major surgery within the last 4 weeks; 15. Patients who are employees at the investigational center, relatives or spouse of the investigator.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified