Clinical trial NCT00943449: 4SC-201 (Resminostat) and Sorafenib in Advanced Hepatocellular Carcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma
Sorafenib
HDAC
4SC-201
Phase II
Resminostat
Lead sponsor: 4SC AG
Sponsor class: INDUSTRY
First posted: 2009-07-22
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine whether 4SC-201 alone or in combination with Sorafenib is effective and safe in the treatment of hepatocellular carcinoma in patients refractory to Sorafenib monotherapy.


Eligibility criteria: Main Inclusion Criteria:

* Advanced stage hepatocellular carcinoma
* Patients exhibiting progressive disease under Sorafenib treatment
* Child-Pugh class A and B. Only patients with Child-Pugh index class B of not more than 7 will be included
* ECOG performance status 0, 1 or 2
* Precedent first-line treatment with Sorafenib minimum continuous dosing of 400 mg per day for at least 8 weeks

Main Exclusion Criteria:

* 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
* Renal failure requiring hemo- or peritoneal dialysis
* Known central nervous system (CNS) tumors including symptomatic brain metastasis
* Child-Pugh index class B in combination with more than slight ascites or hepatic encephalopathy \> Grade I
* Pregnant or breastfeeding women
* Sorafenib intolerance
* Major surgery within the last 4 weeks

Primary outcomes:
measure: Progression Free Survival Rate (PFSR) of repeated oral doses of 4SC-201 and of the treatment combination of Sorafenib plus 4SC-201
timeFrame: 12 weeks
Secondary outcomes:
measure: To establish the MTD of 4SC-201 in combination with Sorafenib
timeFrame: 12 weeks
measure: To investigate the safety and tolerability of repeated oral doses of 4SC-201 and of the treatment combination of ascending repeated oral doses of 4SC-201 and Sorafenib
timeFrame: 12 weeks
measure: To investigate biomarkers
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: ONKOPLUS Beratung und Hilfe für Menschen mit Krebs
city: Essen
country: Germany
facility: Universitätsklinikum Essen (Innere Klinik/Tumorforschung und Zentrum für Innere Medizin)
city: Halle
country: Germany
facility: Medizinische Fakultät der Martin-Luther-Universität Halle-Wittenberg (Klinik und Poliklinik für Innere Medizin I)
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf (I. Medizinische Klinik und Poliklinik)
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg (Medizinische Universitätsklinik/Innere Medizin IV/Nationales Centrum für Tumorerkrankungen)
city: Mainz
country: Germany
facility: Johannes Gutenberg-Universität Mainz (I. Medizinische Klinik und Poliklinik)
city: Munich
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München (Medizinische Klinik und Poliklinik II/Gastroenterologie)
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen (Medizinische Klinik/Innere Medizin I)
city: Bologna
country: Italy
facility: l'Azienda Ospedaliero-Universitaria di Bologna-Policlinico S. Orsola Malpighi
city: Genova
country: Italy
facility: l'Università degli Studi di Genova (Dipartimento di Medicina Interna e Specialità Mediche)
city: Milano
country: Italy
facility: Istituto Europea di Oncologia EIO
city: Napoli
country: Italy
facility: A.O.R.N. Monaldi-Cotugno-CTO
city: Padova
country: Italy
facility: l'Azienda Ospedaliera di Padova and l'Istituto Oncologico Veneto IOV
city: Palermo
country: Italy
facility: l'Ente "Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone"
city: Rozzano-Milano
country: Italy
facility: L'Istituto Clinico Humanitas-Humanitas Mirasole S.p.A.
Study officials:
affiliation: Medizinische Universitäts-Klinik Tübingen
name: Michael Bitzer, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bitzer M, Horger M, Giannini EG, Ganten TM, Worns MA, Siveke JT, Dollinger MM, Gerken G, Scheulen ME, Wege H, Zagonel V, Cillo U, Trevisani F, Santoro A, Montesarchio V, Malek NP, Holzapfel J, Herz T, Ammendola AS, Pegoraro S, Hauns B, Mais A, Lauer UM, Henning SW, Hentsch B. Resminostat plus sorafenib as second-line therapy of advanced hepatocellular carcinoma - The SHELTER study. J Hepatol. 2016 Aug;65(2):280-8. doi: 10.1016/j.jhep.2016.02.043. Epub 2016 Mar 4.