Trial document




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  DRKS00000376

Trial Description

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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.

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Trial Acronym

SHELTER (Studien-Nr. / Study No. 4SC-201-1-2009)

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URL of the Trial

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Brief Summary in Lay Language

A proof-of-concept phase II study to evaluate efficacy, safety and pharmacokinetics of resminostat (4SC-201) and the treatment combination of sorafenib plus resminostat (4SC-201) in patients with hepatocellular carcinoma exhibiting progressive disease under sorafenib treatment. Resminostat is a new histone-deacetylase inhibitor currently under clinical investigation in various oncological indications, i.e. resminostat is not a marketed product until now.
Preclinical studies including HCC cell lines and animal tumor models demonstrate promising signs of efficacy either with treatment of resminostat alone or in the combination with sorafenib. The aim of this study is to explore, if patients who progress under sorafenib therapy in first-line treatment will show signs of efficacy either with treatment of resminostat alone or in the combination treatment with resminostat and sorafenib in second-line therapy. Furthermore, safety, tolerability, pharmacokinetic and pharmacodynamic parameters will be investigated.

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Brief Summary in Scientific Language

The SHELTER-study is a multi-center, open-label, non-randomized, two-arm parallel group clinical trial. The two treatment arms to receive:

Arm A Dose Escalation Phase: Up to 24 patients will be treated with a combination of 4SC-201 and Sorafenib with different dosages each, to evaluate the maximum tolerated dose (MTD) and to evaluate a potential dose limiting toxicity (DLT) of 4SC-201 and Sorafenib in combination.

Arm A Maintenance Phase: Up to 25 patients (an initial cohort of 15 patients, and an optional extension with additional 10 patients) will be treated with 4SC-201 plus Sorafenib.

Arm B: Up to 25 patients (an initial cohort of 15 patients, and an optional extension with additional 10 patients) will be treated with 4SC-201 alone.

Tumor staging in Arm A and Arm B will be done after 3 and after 6 treatment cycles. Each cycle is to include repeated 4SC-201 doses for 5 consecutive days followed by a 9-day rest period. The main phase of the study will be finalized after 6 treatment cycles. In case of medical benefit after 6 treatment cycles, patients will be treated further on.
The study comprises two different and independent treatment arms, which will not be compared in a statistical manner to each other. The study aims at the identification of the clinical efficacy of each of the study treatment arms individually.

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Organizational Data

  •   DRKS00000376
  •   2010/04/19
  •   2009/07/21
  •   no
  •   Approved
  •   155/2009AMG1, Ethik-Kommission an der Medizinischen Fakultät der Eberhard-Karls-Universität und am Universitätsklinikum Tübingen
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Secondary IDs

  •   2009-010760-42 
  •   NCT00943449  (ClinicalTrials.gov)
  •   4035162 
  •   4SC-201-1-2009 
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Health Condition or Problem studied

  •   C22.0 -  Malignant neoplasm: Liver cell carcinoma
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Interventions/Observational Groups

  •   Arm A: combination therapy of resminostat (4SC-201) + sorafenib.
    First step: dose escalation of resminostat (4SC-201) + sorafenib
    Second step: after determination of MTD, therapy of patients on MTD level.
    Both study drugs, resminostat and sorafenib, will be orally administered. Resminostat will be given once-daily in 2-week cycles consisting of 5 consecutive treatment days followed by a 9-day rest period. Sorafenib will be given twice-daily continuously.
  •   Arm B: 600 mg resminostat (4SC-201); mono therapy
    resminostat will be orally administered. Resminostat will be given once-daily in 2-week cycles consisting of 5 consecutive treatment days followed by a 9-day rest period.
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Characteristics

  •   Interventional
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  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Parallel
  •   II
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Primary Outcome

Progression-free survival rate after 12 weeks treatment

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Secondary Outcome

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Countries of Recruitment

  •   Germany
  •   Italy
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Locations of Recruitment

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Recruitment

  •   Actual
  •   2009/08/06
  •   48
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

- Advanced stage hepatocellular carcinoma.
- 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.

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Exclusion Criteria

- Previous or concurrent cancer that is distinct in primary site or histology from HCC, except for 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.

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Addresses

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    • 4SC AG
    • Am Klopferspitz 19a
    • 82152  Planegg-Martinsried
    • Germany
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    • 4SC AG
    • Mr.  Dr. med.  Bernhard  Hauns 
    • Am Klopferspitz 19a
    • 82152  Planegg-Martinsried
    • Germany
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    • 4SC AG
    • Mr.  Dr. med.  Bernhard  Hauns 
    • Am Klopferspitz 19a
    • 82152  Planegg-Martinsried
    • Germany
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Sources of Monetary or Material Support

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    • 4SC AG
    • Am Klopferspitz 19a
    • 82152  Planegg-Martinsried
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2013/07/02
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.