Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12606000117516
Ethics application status
Approved
Date submitted
30/03/2006
Date registered
3/04/2006
Date last updated
13/08/2007
Type of registration
Prospectively registered

Titles & IDs
Public title
Predictive value of ABCB1 genotypes on dose adjustment of imatinib in patients with GIST (Gastro-Intestinal Stromal Tumour) and CML (Chronic Myeloid Leukaemia)
Scientific title
Predictive value of ABCB1 genotypes on dose adjustment of imatinib in patients with GIST(Gastro-Intestinal Stromal Tumour) and CML (Chronic Myeloid Leukaemia)
Secondary ID [1] 253 0
HGWH0006
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patients revieving treatment with imatinib, currently CML (Chronic Myeloid Leukaemia) and GIST (Gastro-Intestinal Stromal Tumour) 1082 0
Condition category
Condition code
Cancer 1162 1162 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The study will correlate the toxicity-adjusted dose of imatinib after 3 months of therapy with polymorphisms of drug elimination genes, particularly ABCB1 (MDR1). Patients will be asked to give a single blood sample for genotyping (at any time) and we will collect clinical data on dose and toxicity retrospectively from medical records.
Intervention code [1] 963 0
None
Comparator / control treatment
No comparator.
Control group

Outcomes
Primary outcome [1] 1567 0
To determine whether ABCB1 genotype correlates with toxicity-adjusted dose of imatinib
Timepoint [1] 1567 0
At 3 months +/- 14 days
Secondary outcome [1] 2819 0
To examine correlations between ABCB1 genotype and toxicity grade according to CTC criteria.
Timepoint [1] 2819 0
Timepoint is 3 months +/- 14days.
Secondary outcome [2] 2820 0
To examine the correlation between toxicity-adjusted dose and CTC toxicity criteria with genotype of other drug elimination genes such as organic anion transporter proteins (OATP) and other biliary efflux proteins such as MRP2, BCRP and other drug elimination genes that may be found to be important in the future.
Timepoint [2] 2820 0
Timepoint is 3 months +/- 14days.
Secondary outcome [3] 2821 0
To confirm findings from a previous study.
Timepoint [3] 2821 0
Timepoint is 3 months +/- 14days.

Eligibility
Key inclusion criteria
ECOG 0, 1 or 2 at start of treatment with imatinib• Medication records of the first 3 months ± 14 days of treatment must be available • Starting dose needs to be either greater than or equal to 600 mg or starting dose of 400 mg if there was a dose reduction required due to toxicity within the first 3 months period of treatment with imatinib• No chemotherapy, biological treatment or any other investigational drug within 28 days of treatment start• Adequate haematological function as determined within the preceeding14 days, ANC >/= 1.5 x109/l as well as Platelets >/= 100 x109/l• Adequate liver and renal function defined as serum bilirubin concentration less than 1.5 x ULN, AST and ALT less than 2.5 x ULN, serum creatinine concentration less than 1.5 x ULN• No known primary liver disease and no other severe or uncontrolled concurrent medical condition within the first 3 months of treatment with imatinib.• Patients who have participated on other clinical studies of imatinib will be suitable for this study.• Being treated with Imatinib for more than 10 weeks • Signed informed consent.
Minimum age
18 Years
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who are unable to sign informed consent• Patients who have had less than 400 mg of imatinib at start of treatment• Patient included in the initial Glisest study • Patients unable to give blood• Patients who had a bone-marrow-transplantation prior to imatinib treatment• Patients who had no blood sample taken and available for genotyping prior to bone-marrow-transportation.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Both
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
10/04/2006
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 1270 0
Charities/Societies/Foundations
Name [1] 1270 0
Cancer Insitute Clinical Fellowship
Country [1] 1270 0
Australia
Primary sponsor type
Individual
Name
Investigator Initiated - A/Professor Howard Gurney and Dr Josef Klumpen
Address
Country
Secondary sponsor category [1] 1125 0
None
Name [1] 1125 0
nil
Address [1] 1125 0
Country [1] 1125 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 2602 0
Sydney West Area Health Service - Westmead Campus
Ethics committee address [1] 2602 0
Ethics committee country [1] 2602 0
Australia
Date submitted for ethics approval [1] 2602 0
Approval date [1] 2602 0
Ethics approval number [1] 2602 0

Summary
Brief summary
The purpose of this study is to examine the genotypes of ABCB1 (a type of gene found in your cells) in a larger group of patients to test whether the correlation (matching of genes with more side effects from drug treatment) seen in the previous small study are true. The primary (main) endpoint will be a correlation of ABCB1 genotype and imatinib dose after three months of therapy that will allow for dose adjustments based on toxicity (side effects). The larger patient numbers will also allow a haplotype (gene) analysis to be done.

The importance of dose individualisation is illustrated by studies that show better outcomes for cancer patients who have post-treatment dose adjustments based on therapeutic drug monitoring or on toxicity. However, with these methods, the optimum dose for each patient is often not reached until after the majority of the treatment course has been given. A correlation between ABCB1 genotype and toxicity-adjusted dose has practical significance since a simple blood test could allow effective dose selection in individuals.

Approximately 300 patients will be required.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35439 0
Address 35439 0
Country 35439 0
Phone 35439 0
Fax 35439 0
Email 35439 0
Contact person for public queries
Name 10152 0
Rada Kusic
Address 10152 0
Sydney West Cancer Trials Centre
Medical Oncology Division
Westmead Hospital
Hawkesbury Road
Westmead NSW 2145
Country 10152 0
Australia
Phone 10152 0
+61 2 98458935
Fax 10152 0
+61 2 98916035
Email 10152 0
[email protected]
Contact person for scientific queries
Name 1080 0
Dr Heinz-Josef Klümpen
Address 1080 0
Sydney West Cancer Trials Centre
Medical Oncology Division
Westmead Hospital
Hawkesbury Road
Westmead NSW 2145
Country 1080 0
Australia
Phone 1080 0
+61 2 98456954
Fax 1080 0
+61 2 98916035
Email 1080 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.