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Trial registered on ANZCTR


Registration number
ACTRN12613000058774
Ethics application status
Approved
Date submitted
7/12/2012
Date registered
16/01/2013
Date last updated
16/01/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Mitotane Therapeutic Drug Monitoring Study: Assessing Mitotane Pharmacodynamics in Adrenocortical Cancer in Children and Adults
Scientific title
Mitotane Pharmacodynamics in Adrenocortical Cancer in Children and Adults
Secondary ID [1] 281630 0
None
Universal Trial Number (UTN)
Trial acronym
Mitotane TDM Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adrenocortical cancer 287916 0
Condition category
Condition code
Cancer 288292 288292 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Mitotane dose adjustment based on plasma level of mitotane and metabolites, to achieve ideal mitotane plasma level (14-20 mg/L) as quickly as possible, and minimise adverse impact of overdosing. (Mitotane is administered orally daily in single or divided doses, starting at 1 or 2 g/day,and the dose required is highly variable and unpredictable). Treatment duration is at the discretion of the treating clinician.
Intervention code [1] 286163 0
Treatment: Drugs
Comparator / control treatment
none
Control group
Uncontrolled

Outcomes
Primary outcome [1] 288468 0
To determine the relationship between plasma mitotane and metabolite levels and toxicity (as assessed clinically), and confirm the published relationship with response.
Timepoint [1] 288468 0
Continually from start until end of treatment period
Secondary outcome [1] 300251 0
To identify factors that account for variability in mitotane kinetics.
- we will correlate mitotane and metabolite pharmacokinetic (PK) parameters with phenotypic factors, including age, gender and body mass index. We anticipate that age, gender and body mass index will partly correlate with PK.
Timepoint [1] 300251 0
Continually from start until end of treatment period
Secondary outcome [2] 300252 0
Assess the role of mitotane metabolites in contribution to toxicity, by correlating plasma levels with clinical assessments
Timepoint [2] 300252 0
Continually from start until end of treatment period
Secondary outcome [3] 300253 0
To provide a precise mitotane therapeutic drug monitoring process that rapidly achieves trough levels in the range 14-20mg/L, by frequent, informed dose escalation.

Timepoint [3] 300253 0
Continually from start until end of treatment period
Secondary outcome [4] 300684 0
To achieve Ideal plasma level as soon as possible (preferably within 4 weeks) after starting mitotane, and maintained without exceeding the ideal range
Timepoint [4] 300684 0
Continually from start until end of treatment period

Eligibility
Key inclusion criteria
1. Adrenocortical carcinoma, any stage.
2. Treating physician is of the opinion that Mitotane therapy is indicated for the patient
3. Normal haematological parameters
4. Normal liver function
5. Adequate renal function
6. Eastern Co-operative Oncology Group (ECOG) performance status 0-2 .
7. No other significant medical illness.
8. Geographically accessible and physically capable of completing study investigations as required.
9. Informed consent for study investigations.
Minimum age
0 Years
Maximum age
100 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
none

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)
eligible subjects will be invited
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint(s)
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
Simple statistical tests (chi square, Pearson correlation, etc) will be used to determine the relationship between mitotane and metabolite levels and toxicity, and confirm the published relationship with response.

To identify factors that account for variability in mitotane kinetics, mitotane and metabolite pharmacokinetic parameters will be correlated with phenotypic factors, including age, gender and body mass index. A PD model for toxicity will be derived using independent variables of dose, plasma level and patient characteristics. WinNonLin, Statistica or similar non-linear modeling software will be used.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 286438 0
University
Name [1] 286438 0
Hunter Medical Research Institute
Address [1] 286438 0
Locked bag 1000
New Lambton 2305
NSW
Country [1] 286438 0
Australia
Primary sponsor type
Hospital
Name
Calvary Mater Newcastle
Address
Edith St
Waratah, 2298
NSW
Country
Australia
Secondary sponsor category [1] 285224 0
None
Name [1] 285224 0
none
Address [1] 285224 0
Country [1] 285224 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288514 0
HNE Health HREC
Ethics committee address [1] 288514 0
Locked Bag 1
New Lambton, 2305
NSW
Ethics committee country [1] 288514 0
Australia
Date submitted for ethics approval [1] 288514 0
Approval date [1] 288514 0
Ethics approval number [1] 288514 0

Summary
Brief summary
Mitotane is the only systemic treatment available for advanced adrenocortical cancer and is toxic, with variable pharmacokinetics (variable drug metabolism between patients). This study aims to achieve ideal plasma levels of the drug quickly by adjustment of the dose based on plasma level, and maintain the plasma level within the ideal range by regular blood level monitoring and dose adjustment. We also aim to study factors that contribute to variability between patients in their metabolism of the drug, and confirm a relationship between drug level and anticancer effect. As a consequence of this study we aim to provide a high quality therapeutic drug monitoring service for clinicians and patients with this disease in Australia.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 36446 0
Prof Stephen Ackland
Address 36446 0
Medical Oncology
Calvary Mater Newcastle Hospital,
and
Hunter Cancer Research Alliance
Locked Bag 7
Hunter Region Mail Centre, 2310
NSW
Country 36446 0
Australia
Phone 36446 0
+61249211146
Fax 36446 0
Email 36446 0
stephen.ackland@newcastle.edu.au
Contact person for public queries
Name 36447 0
Prof Stephen Ackland
Address 36447 0
Medical Oncology
Calvary Mater Newcastle Hospital,
and
Hunter Cancer Research Alliance
Locked Bag 7
Hunter Region Mail Centre, 2310
NSW
Country 36447 0
Australia
Phone 36447 0
+61249211146
Fax 36447 0
Email 36447 0
stephen.ackland@newcastle.edu.au
Contact person for scientific queries
Name 36448 0
Ms Madhu Garg
Address 36448 0
Medical Oncology
Calvary Mater Newcastle Hospital,
and
Hunter Cancer Research Alliance
Locked Bag 7
Hunter Region Mail Centre, 2310
NSW
Country 36448 0
Australia
Phone 36448 0
+61249211150
Fax 36448 0
Email 36448 0
madhu.garg@newcastle.edu.au

No information has been provided regarding IPD availability
Summary results
No Results