Clinical trial NCT00900354: Pharmacokinetics of Dactinomycin in Young Patients With Cancer
Official title: Pharmacokinetics of Actinomycin D in Children With Cancer
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Unspecified Childhood Solid Tumor, Protocol Specific
Keywords: unspecified childhood solid tumor, protocol specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2009-05-12
Enrollment: 50
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no

Brief summary: RATIONALE: Studying samples of blood in the laboratory from patients with cancer receiving dactinomycin may help doctors learn how dactinomycin works in the body and how patients will respond to treatment.

PURPOSE: This laboratory study is evaluating the pharmacokinetics of dactinomycin in young patients with cancer.

Detailed description: OBJECTIVES:

* Determine the pharmacokinetics (PKs) of dactinomycin in pediatric patients with cancer.
* Determine the degree of interpatient variation in the PKs of this drug.
* Determine the influence of characteristics such as age, tumor type, and concurrent therapy on drug PKs in these patients.
* Correlate drug PKs with clinical response and toxicity observed in these patients, focusing particularly on the incidence of severe liver toxicity or veno-occlusive disease.
* Correlate pharmacogenetic variability with clinical and PK data.

OUTLINE: This is a multicenter study.

Patients undergo blood collection for pharmacokinetic sampling of dactinomycin at baseline (prior to the initiation of dactinomycin) and periodically during course 1 of chemotherapy. An additional blood sample is obtained before or after treatment for the collection of peripheral blood lymphocytes. DNA from these cells is isolated and investigated for genetic variation in genes relevant to the pharmacology of dactinomycin. Plasma concentrations of dactinomycin are determined by liquid chromatography mass spectrometry analysis.

Patients are followed for 2 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of cancer
* Currently being treated with dactinomycin on a clinical trial at a United Kingdom Children's Cancer Study Group center

PATIENT CHARACTERISTICS:

* Single- or double-lumen central venous catheter or portacath in place

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Primary outcomes:
measure: Pharmacokinetics (PKs) of dactinomycin
measure: Degree of interpatient variation of drug PKs
measure: Influence of characteristics such as age, tumor type, and concurrent therapy on drug PKs
measure: Correlation of drug PKs with clinical response and toxicity, particularly the incidence of severe liver toxicity or veno-occlusive disease
Secondary outcomes:
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: Our Lady's Hospital for Sick Children Crumlin
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: England
city: Bristol
country: United Kingdom
facility: Institute of Child Health at University of Bristol
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Children's Hospital, Alder Hey
state: England
city: London
country: United Kingdom
facility: Middlesex Hospital
state: England
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
state: England
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Sir James Spence Institute of Child Health at Royal Victoria Infirmary
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: University of Newcastle-Upon-Tyne Northern Institute for Cancer Research
state: England
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
state: England
city: Oxford
country: United Kingdom
facility: Oxford Radcliffe Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Children's Hospital - Sheffield
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Belfast
country: United Kingdom
facility: Royal Belfast Hospital for Sick Children
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Royal Aberdeen Children's Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Sick Children
state: Scotland
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Sick Children
state: Scotland
city: Cardiff
country: United Kingdom
facility: Childrens Hospital for Wales
state: Wales
Study officials:
affiliation: University of Newcastle Upon-Tyne
name: Gareth Veal
role: STUDY_CHAIR
affiliation: University of Newcastle Upon-Tyne
name: Alan Boddy, PhD
References:
citation: Kim HY, Veal GJ, Zhou F, Boddy AV. The role of solute carrier (SLC) transporters in actinomycin D pharmacokinetics in paediatric cancer patients. Eur J Clin Pharmacol. 2018 Dec;74(12):1575-1584. doi: 10.1007/s00228-018-2544-z. Epub 2018 Aug 30.