AYAPK- Adolescents and Young Adults PK

• Research type

  Research Study

• Full 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

• IRAS ID

  57703

• Contact name

  Beatrice Seddon

• Sponsor organisation

  Australian Sarcoma Group (ASSG)

• Eudract number

  2011-005554-62

• ISRCTN Number

  ISRCTN

• Research summary

  In several tumour types AYAs (Adolescents & Young Adults) have a worse prognosis than children with the same disease. Analysis by gender shows that for osteosarcoma (OS), Ewing family of tumours (EFT) and Hodgkin lymphoma (HL), (all chemosensitive tumours with peak incidence in AYAs) the excess mortality compared to children with the same diagnoses is confined to males. Doxorubicin is a critical drug in the treatment of OS, EFT and HL. While its effect is dose dependent, very little is known about its pharmacokinetics (PK), and dosing is empiric, based on body surface area. There is evidence to suggest age, gender, body composition and adiposity (body fat composition) can affect doxorubicin handling. There have been no systematic studies examining the effect of puberty with the attendant gender specific changes in body composition on PK or AYA cancer outcomes. This study will recruit patients with osteosarcoma, Ewing family of tumours and Hodgkin lymphoma, across paediatric and adult oncology sites where treatment regimens are accepted standard of care. We will characterise doxorubicin/doxorubicinol pharmacokinetics (PK; how the body deals with the drug) and measure pharmacodynamics (PD; effect of drug on the body) as measured by chemotherapy toxicity and tumour response. We will evaluate the effect of gender on doxorubicin/doxorubicinol PK in AYA patients with EFT, OS or HL and look for an association between gender and PD. Among children and AYA with EFT and OS receiving standardised chemotherapy regimens, we will evaluate the effect of gender and pubertal stage on PK. We will explore the relationship between PK and PD in children and AYA with EFT, OS or HL. We will explore the relationship between chemotherapy toxicity and tumour response in children and AYA with EFT, OS or HL. Anthropometric measures of body composition will be recorded. Samples for further pharmacogenomic analysis will also be collected.

• REC name

  London - Central Research Ethics Committee

• REC reference

  12/LO/0286

• Date of REC Opinion

  9 Mar 2012

• REC opinion

  Favourable Opinion