Trial registered on ANZCTR


Trial ID
ACTRN12609000956202
Ethics application status
Approved
Date submitted
28/10/2009
Date registered
5/11/2009
Type of registration
Prospectively registered

Titles & IDs
Public title
Pharmacokinetics and Pharmacodynamics of Doxorubicin in Children, Adolescents and young adults with Newly Diagnosed Osteosarcoma, Ewing Family of Tumours and Hodgkin Lymphoma A Multi-Institutional Cross-Discipline Non-Therapeutic Study
Scientific title
Pharmacokinetics and Pharmacodynamics of Doxorubicin in Children, Adolescents and young adults with Newly Diagnosed Osteosarcoma, Ewing Family of Tumours and Hodgkin Lymphoma A Multi-Institutional Cross-Discipline Non-Therapeutic Study
Secondary ID [1] 1123 0
Australasian Sarcoma Study Group Number 3-10 AYA PK (ASSG 03-10 AYA PK)
Universal Trial Number (UTN)
Trial acronym
ASSG 03-10 AYAPK
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteosarcoma 252073 0
Ewing Family of Tumours 252126 0
Hodgkin Lymphoma 252127 0
Condition category
Condition code
Cancer 252278 252278 0 0
Children's - Leukaemia & Lymphoma
Cancer 252279 252279 0 0
Bone
Cancer 252280 252280 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental drug treatments are not part of this study. Patients will receive chemotherapy that is standard of care at their hospital. Blood samples for pharmacokinetics will be collected immediately prior to cycle 1 doxorubicin administration and at 0.5, 1, 3, & 6 hours after the end of the infusion, then at 24, 48 and 72 hours. Pharmacodynamics will be assessed using body composition assessments before patients commence chemotherapy. Body composition will be assessed by height and weight; bioelectric impedance analysis; X-ray of the wrist to estimate bone age and dual energy X-ray absorptiometry (DEXA) scan.
Intervention code [1] 241466 0
Other interventions
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 253148 0
To evaluate the effect of gender on the pharmacokinetics of doxorubicin in Adolescent and Young Adult with newly diagnosed Hodgkin lymphoma, osteosarcoma and Ewing family of tumours by comparing doxorubicin concentration-time curve area under the curve (AUC) against gender.
Timepoint [1] 253148 0
Cycle 1 of first infusion doxorubicin treatment
Secondary outcome [1] 262047 0
To evaluate the effect of gender and pubertal stage on the pharmacokinetics of doxorubicin in children and Adolescent and Young Adult (collectively) with newly diagnosed osteosarcoma and Ewing family of tumours by comparing doxorubicin concentration-time curve area under the curve (AUC) against gender.
Timepoint [1] 262047 0
Cycle 1 first infusion of doxorubicin treatment
Secondary outcome [2] 262048 0
To explore the relationship between doxorubicin pharmacokinetics and pharmacodynamics where pharmacodynamics is measured by worst toxicity grade and tumour response
Timepoint [2] 262048 0
Toxicity assessment at end of Cycle 1; response assessment at end of chemotherapy
Secondary outcome [3] 262049 0
To explore the relationship between toxicity and tumour response. Toxicity is measured using the Common Terminology Criteria for Adverse Events (CTCAE) version 3. Tumour response will be assessed using the hospital's standard response assessment measures, which depending on the disease may include post-resection tumour necrosis evaluation or radiological and nuclear imaging.
Timepoint [3] 262049 0
Toxicity assessment at end of Cycle 1; response assessment at end of chemotherapy

Eligibility
Key inclusion criteria
Newly diagnosed with osteosarcoma, Ewing family of tumours or Hodgkin lymphoma;
aged between 1 year and 40 years of age; planned treatment involves a standard doxorubicin-containing regimen; written informed consent from patient and/or patient’s parent or legal guardian
Minimum age
1 Years
Maximum age
40 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Impaired hepatic function such as known chronic liver disease, evidence of impaired synthetic function or transaminases raised >5 x normal; significant uncontrolled systemic illness as judged by investigator; females who are pregnant or breast feeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All patients diagnosed with Hodgkin lymphoma, osteosarcoma and Ewing family of tumours scheduled to receive chemotherapy including doxorubicin will be considered for the study
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
nonrandomised
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
not applicable
Phase
Not Applicable
Type of endpoint(s)
Pharmacokinetics / pharmacodynamics

Recruitment
Anticipated date of first participant enrolment
1/07/2010
Actual date of first participant enrolment
Anticipated date last participant enrolled
Actual date last participant enrolled
Anticipated date of last data collection
Actual date of last data collection
Target sample size
210
Actual sample size
Recruitment status
Recruiting
Recruitment in Australia
Recruitment state(s)
NSW,VIC,QLD,WA
Recruitment postcode(s) [1] 2171 0
3000
Recruitment postcode(s) [2] 2172 0
3002

Funding & Sponsors
Funding source category [1] 243938 0
Government body
Name [1] 243938 0
Victorian Cancer Agency
Address [1] 243938 0
12 Victoria Street, Carlton, Victoria 3053
Country [1] 243938 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Sarcoma Study Group
Address
Peter MacCallum Cancer Centre
Research Division Level 2
St Andrews Place East Melbourne Vic 3002
Country
Australia
Secondary sponsor category [1] 251293 0
None
Name [1] 251293 0
Address [1] 251293 0
Country [1] 251293 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 244051 0
Peter MacCallum Cancer Centre
Ethics committee address [1] 244051 0
St Andrews Place, East Melbourne, Victoria 3002
Ethics committee country [1] 244051 0
Australia
Date submitted for ethics approval [1] 244051 0
23/11/2009
Approval date [1] 244051 0
04/03/2010
Ethics approval number [1] 244051 0
09/73
Ethics committee name [2] 244052 0
Royal Childrens Hospital
Ethics committee address [2] 244052 0
Flemington Road, Parkville, Victoria 3052
Ethics committee country [2] 244052 0
Australia
Date submitted for ethics approval [2] 244052 0
23/11/2009
Approval date [2] 244052 0
23/08/2010
Ethics approval number [2] 244052 0
29135 A
Ethics committee name [3] 259257 0
Albury Wodonga Joint Hospitals Ethics Committee (Border Medical Oncology)
Ethics committee address [3] 259257 0
Albury Hospital, Borella Rd, Albury NSW 2640
Ethics committee country [3] 259257 0
Australia
Date submitted for ethics approval [3] 259257 0
Approval date [3] 259257 0
17/02/2010
Ethics approval number [3] 259257 0
342/10/2
Ethics committee name [4] 259258 0
Royal Childrens Hospital Brisbane
Ethics committee address [4] 259258 0
Level 3, RCH Foundation Building, Royal Children's Hospital
Herston QLD 4029
Ethics committee country [4] 259258 0
Australia
Date submitted for ethics approval [4] 259258 0
Approval date [4] 259258 0
03/02/2010
Ethics approval number [4] 259258 0
HREC/10/QRCH/4
Ethics committee name [5] 259259 0
Childrens' Hospital Westmead (lead site NSW) and Sydney Children's Hospital (multi-site approval)
Ethics committee address [5] 259259 0
Cnr Hawkesbury Rd and Hainsworth St, Westmead NSW 2145

(NB HREC approval via Westmead)
Ethics committee country [5] 259259 0
Australia
Date submitted for ethics approval [5] 259259 0
Approval date [5] 259259 0
25/01/2010
Ethics approval number [5] 259259 0
09/CHW/157 (Multicentre approval)

Summary
Brief summary
Currently the doses of medication given to treat cancer are generally determined by a simple body surface area (BSA) calculation based on weight and height. However, physiological differences between individuals may affect the way cancer drugs are processed by the body, potentially leading to variable dose levels in the body, and differences in toxicity and efficacy between individuals. This study is looking at the way the body processes the drug doxorubicin (this is called pharmacokinetics and pharmacodynamics), to see if gender, stage of puberty, or body composition may impact the effectiveness or toxicity of doxorubicin.

The study focuses on osteosarcoma, Ewing family of tumours and Hodgkin lymphoma because there is some evidence that there may be a difference between males and females in the response to chemotherapy for these cancers. These cancers mainly affect young people, many of whom are undergoing the physical changes of puberty, which are different for males and females.
Trial website
n/a
Trial related presentations / publications
n/a
Public notes

Contacts
Principal investigator
Name 30429 0
Address 30429 0
Country 30429 0
Phone 30429 0
Fax 30429 0
Email 30429 0
Contact person for public queries
Name 13676 0
Dr Sally Whyte
Address 13676 0
Peter MacCallum Cancer Centre
Research Division Level 2
St Andrews Place East Melbourne Victoria 3002
Country 13676 0
Australia
Phone 13676 0
+61 3 9656 3605
Fax 13676 0
+61 3 9656 5875
Email 13676 0
sarcoma@petermac.org
Contact person for scientific queries
Name 4604 0
Dr Sally Whyte
Address 4604 0
Peter MacCallum Cancer Centre Research Division Level 3 St Andrews Place East Melbourne Victoria 3002
Country 4604 0
Australia
Phone 4604 0
+61 3 9656 3605
Fax 4604 0
+61 3 9656 5875
Email 4604 0
sarcoma@petermac.org