Vorinostat in Children

• Status: Completed
• Trial end date: 2017-03-24
• Target enrollment: 0
• Participant gender: All

Summary

The aim of this study is to define a dose recommendation of vorinostat in pediatric oncology, to determine pharmacokinetics of vorinostat in children, determine response rates, safety and feasibility.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Center for Tumor Diseases, Heidelberg
• Collaborators: Merck Sharp & Dohme Corp.; University Hospital Heidelberg
• Treatments: Vorinostat

Criteria

Inclusion Criteria:

• Children and adolescents (3-18 years) with relapsed or therapy-refractory solid tumor, lymphoma or leukemia following standard first-line or relapse protocols in pediatric oncology

• Diagnosis confirmed by one of the Pathological, Radiological or Study Reference Centers recognized by the GPOH

• No other simultaneous anti-neoplastic treatment or radiation during the study and 1 months before enrolment

• Sufficient general condition (Lansky Score >50%)

• Life expectancy > 3 months

• Liver enzymes (ALT or AST) < 5x upper limit of normal reference value, bilirubin and creatinine < 3x upper limit of normal reference value

• Solid tumors: leukocytes > 2000/µl, thrombocytes > 50.000/µl and adequate bone marrow function to permit evaluations of hematopoietic toxicity

• No CTC grade 3 or 4 toxicity from previous treatments

• Normal ECG

• Written informed consent of the legal representatives and the patient if the patient is able to understand the study situation and to give consent (must be available before enrolment in the trial)

• Women with childbearing potential agree to use adequate contraception or to abstain from heterosexual activity throughout the study, starting with Visit 1.

• Sexually active male patient agrees to use an adequate method of contraception for the duration of the study

• Solid tumors: measurable disease activity according to RECIST criteria

Exclusion Criteria:

• History of deep vein thrombosis or pulmonary embolism

• Pregnancy and lactation

• Patient with concomitant treatments and/or anti-neoplastic treatment such as chemotherapy, immune therapy, and differentiation therapy, other targeted therapy, radiation. The use of valproic acid as prior antiepileptic therapy is allowed with a 30-day washout period.

• Prior exposure to Histone Deacetylase Inhibitors

• Known active HBV, HCV or HIV infection

• Patient with concomitant treatments such as amber [Hypericum perforatum], plant extracts, vitamins, and other anti-oxidative compounds

• Participation in other clinical trials or observation period of competing trials, respectively

• Patient is unable to swallow vorinostat suspension or capsules

• Patient on coumarin-derivative anticoagulants

• Any other medication which could accentuate known dose-dependent adverse effects of the study drug, for instance bone marrow depression or QT-prolongation