Relapsed of progressive solid tumor, lymphoma, or leukemia in children and adolescents aage 3-18 years MedDRA version: 18.0 Level: HLGT Classification code 10024324 Term: Leukaemias System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 18.0 Level: PT Classification code 10025310 Term: Lymphoma System Organ
Conditions
Interventions
Product Name: Vorinostat
Product Code: 0006-0568-40
Pharmaceutical Form: Capsule
INN or Proposed INN: Vorinostat
CAS Number: 149647-78-9
Sponsors
University Hospital Heidelberg
Eligibility
Sex/Gender
All
Inclusion 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 two weeks before enrolment ? Sufficient general condition (Lansky Score >50%) ? Life expectancy > 3 months ? Liver enzymes (ALT or AST) 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 (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 Are the trial subjects under 18? yes Number of subjects for this age range: 50 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion 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 14-day washout period. Washout will be ensured by determining valproic acid plasma level before enrolment.? 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine a safe dose for the routine application of oral vorinostat (involving dose escalation) in children and adolescents (3-18 years) with relapsed/refractory solid tumor, lymphoma or leukemia;Primary end point(s): safe dose for the routine application of oral vorinostat (involving dose escalation) in children and adolescents (3-18 years) with relapsed/refractory solid tumor, lymphoma or leukemia;Timepoint(s) of evaluation of this end point: weekly; Secondary Objective: To determine the distribution of individual maximum tolerated doses (MTD), which is the maximum dose with no grade 3 or 4 toxicity according to CTC criteria. To determine the pharmacokinetics of oral vorinostat in children and adolescents (3 – 18 years) with relapsed/refractory solid tumor, lymphoma or leukemia To determine antitumor effectiveness of vorinostat as measured by objective response rate in children and adolescents (3-18 years) with relapsed/refractory solid tumor, lymphoma or leukemia. Response (CR, PR, SD) will be evaluated in every patient three months after start of treatment with the individual maximum tolerated dose (MTD). To correlate the (HDAC)-inhibiting activity with the dose administered, toxicity, and treatment response. To determine feasibility and safety of oral vorinostat in children and adolescents (3-18 years) with solid tumor, lymphoma or leukaemia. To determine duration of response in responding patients | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? pharmacokinetics and the distribution of individual maximum tolerated doses (MTD), which is the maximum dose with no grade 3 or 4 toxicity according to CTC criteria. ? antitumor effectiveness of vorinostat as measured by treatment response rate. Response will be evaluated in each patient three months after start of treatment with the individual MTD. ? association of the histone deacetylase (HDAC)-inhibiting activity with the dose administered toxicity, and treatment response. ? feasibility and safety ? duration of response in responding patients. Additional biomarker studies for the prediction of vorinostat response (IL-6, IL-10, BMP) induction, basal histone acetylation level) will be performed. ;Timepoint(s) of evaluation of this end point: response 3 months after start of treatment | — |
Countries
Germany
Contacts
Public ContactTrial Center
Nationales Centrum für Tumorerkrankungen Heidelberg
Outcome results
None listed