Vorinostat in Children

NCT01422499 | Completed Phase 1 DMC

• 1 other identifier: NCT-2007-11-02-1004
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Children With Relapsed Solid Tumor, Lymphoma or Leukemia

Keywords

pediatric oncology; relapsed solid tumor; lymphoma; leukemia; vorinostat

Outcome Measures

Primary Outcomes (1)

• To determine a safe dose recommended (SDR) 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.

  A SDR is defined as the highest dose with no ≥ grade 3 toxicity according to CTC criteria (Dose Limiting Toxicity) in no more than 1/50 patient in this study. Dose Limiting Toxicity (DLT) is defined as any grade 3 or 4 toxicity according the CTCAE version 4.0 and judged by the investigator as definitely, probably or possibly related to the study drug. However, all DLTs will be subject to a second assessment by the Coordinating Investigator or a designated person.

  After finding the individual MTD this dose will be applied for 3 months. Patients without progression at first response evaluation will continue treatment for a maximum of 9 months.

Secondary Outcomes (5)

• pharmacokinetics

  d 8, when maximum tolerated dose (MTD) ist reached and after 3 months treatment at MTD

• antitumor effectiveness

  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

  d8, after reaching the MTD and after 3 months treatment at MTD

• safety

  during dose escalation and during 3 months treatment at MTD every week; during prolongation of treatment and follow-up every second week

• duration of response in responding patients

  every 3 months until progression of tumor

Interventions

zolinza/vorinostat DRUG

orally once per day (suspension of 50mg/ml or capsules of 100 mg vorinostat); starting dose will be 180 mg/m²/d; escalated with increments of 50 mg/m²/d every two weeks until dose limiting toxicity (grade 3 or 4 toxicity according to CTC) occurs or up to a maximum dose of 580 mg/m²/d; This dose will then be applied for 3 months. Patients without progression at first response evaluation will continue treatment for a maximum of 9 months.

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Center for Tumor Diseases, Heidelberg: lead
• University Hospital Heidelberg: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (10)

Clinic for Pediatric Oncology, Hematology, Immunology and Clinical Cooperation Unit Pediatric Oncology

Heidelberg, Baden-Wurttemberg, 69198, Germany

Location

Childrens's Hospital, Pediatric Oncology and Hematology

Augsburg, 86156, Germany

Location

Prof. Hess Childrens's Hospital, Pediatric Oncology and Hematology

Bremen, 28205, Germany

Location

University Children's Hospital, Pediatric Oncology and Hematology

Cologne, 50937, Germany

Location

University Childrens's Hospital, Pediatric Oncology and Hematology

Essen, 45122, Germany

Location

University Children's Hospital, Clinic IV

Freiburg im Breisgau, 79106, Germany

Location

Department of Pediatric Oncology and Hematology University Hospital Eppendorf (UKE)

Hamburg, 20246, Germany

Location

University Children's Hospital, Pediatric Oncology and Hematology, MHH

Hanover, 30625, Germany

Location

University Childrens's Hospital, Pediatric Oncology and Hematology

Jena, 07743, Germany

Location

Department of Pediatric Oncology and Hematology University Children's Hospital

Münster, 48149, Germany

Location

Related Publications (2)

• van Tilburg CM, Milde T, Witt R, Ecker J, Hielscher T, Seitz A, Schenk JP, Buhl JL, Riehl D, Fruhwald MC, Pekrun A, Rossig C, Wieland R, Flotho C, Kordes U, Gruhn B, Simon T, Linderkamp C, Sahm F, Taylor L, Freitag A, Burhenne J, Foerster KI, Meid AD, Pfister SM, Karapanagiotou-Schenkel I, Witt O. Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma, or leukemia. Clin Epigenetics. 2019 Dec 10;11(1):188. doi: 10.1186/s13148-019-0775-1.

  PMID: 31823832 DERIVED

• Witt O, Milde T, Deubzer HE, Oehme I, Witt R, Kulozik A, Eisenmenger A, Abel U, Karapanagiotou-Schenkel I. Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma or leukemia. Klin Padiatr. 2012 Oct;224(6):398-403. doi: 10.1055/s-0032-1323692. Epub 2012 Aug 22.

  PMID: 22915450 DERIVED

MeSH Terms

Conditions

Lymphoma; Leukemia

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Olaf Witt, Prof. Dr.

  University Hospital Heidelberg and German Cancer Research Center (DKFZ)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2011
• First Posted: August 24, 2011
• Study Start: March 1, 2012
• Primary Completion: March 24, 2017
• Study Completion: March 24, 2017
• Last Updated: April 11, 2018

Record last verified: 2018-04

Locations

DE (10)