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Trial registered on ANZCTR


Registration number
ACTRN12609000056291
Ethics application status
Approved
Date submitted
23/09/2008
Date registered
23/01/2009
Date last updated
23/01/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effect of cancer progression on the activity of the liver enzyme called CYP2C19 in patients with carcinoma of the gastrointestinal tract using the probe drug proguanil.
Scientific title
The effect of cancer progression on the activity of the liver enzyme called CYP2C19 in patients with carcinoma of the gastrointestinal tract using the probe drug proguanil.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma of the gastrointestinal tract 3735 0
Condition category
Condition code
Cancer 4257 4257 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participating patients will be dispensed with three 200mg doses of the probe drug, proguanil. The patients will be advised to take a single oral dose (200mg) of the probe three hours in advance of each of their next three routine blood tests. These tests may be as little as one week or as much as three months apart.
Intervention code [1] 3449 0
Treatment: Drugs
Comparator / control treatment
There is no comparator or control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 4807 0
To elucidate the biological correlation between CYP2C19 functional activity and cancer progression in patients with carcinoma of the gastrointestinal tract at 3 hours post administration of proguanil.
CYP2C19 functional activity will be measured by plasma samples.Cancer progression is defined as per standard clinical practice.
Timepoint [1] 4807 0
At 3 hours post administration of proguanil
Secondary outcome [1] 8113 0
To evaluate the relationship between CYP2C19 activity and cachexia as measured from plasma samples.
Timepoint [1] 8113 0
All patients will have blood collected at baseline for determination of CYP2C19 genotype and measurement of cytokines interleukin 1 (IL-1), interleukin 6 (IL-6) and tumour necrosis factor (TNF) and C-reactive protein (CRP). 3 hours prior to the patients next three routine blood tests a single oral dose (200mg) of the probe (proguanil) will be administered. The above mentioned determinations will be repeated on each of these occasions.
Secondary outcome [2] 8641 0
To test the hypothesis that there is no association between CYP2C19 activity and circulating markers of inflammation as measured from plasma samples.
Timepoint [2] 8641 0
All patients will have blood collected at baseline for determination of CYP2C19 genotype and measurement of cytokines interleukin 1 (IL-1), interleukin 6 (IL-6) and tumour necrosis factor (TNF) and C-reactive protein (CRP). 3 hours prior to the patients next three routine blood tests a single oral dose (200mg) of the probe (proguanil) will be administered. The above mentioned determinations will be repeated on each of these occasions.

Eligibility
Key inclusion criteria
Diagnosed with cancer
At least 18 years of age
Adequate renal and liver function
Serum creatinine =< 0.12 mg/L
Aspartate transaminase (AST), Alaninine transaminase (ALT) =< 2.0 X upper limit of normal (ULN) for institution
Alkaline phosphatase =< 2.5 X ULN
Total bilirubin =< ULN
Patients must be able to provide informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients receiving medication which is either a CYP2C19 inhibitor or inducer, and where a washout period is not clinically feasible

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



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Not yet 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 outside Australia
Country [1] 1231 0
New Zealand
State/province [1] 1231 0

Funding & Sponsors
Funding source category [1] 3914 0
University
Name [1] 3914 0
University of Auckland
Address [1] 3914 0
Faculty of Medical & Health Sciences
University of Auckland
Private Bag 92019
Auckland 1023
Country [1] 3914 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Faculty of Medical & Health Sciences
University of Auckland
Private Bag 92019
Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 3511 0
None
Name [1] 3511 0
Address [1] 3511 0
Country [1] 3511 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5974 0
New Zealand Northern X Regional Ethics Committee
Ethics committee address [1] 5974 0
Ministry of Health
3rd Floor, Unisys Building
650 Great North Road, Penrose
Private Bag 92 522
Wellesley Street, Auckland
Ethics committee country [1] 5974 0
New Zealand
Date submitted for ethics approval [1] 5974 0
Approval date [1] 5974 0
10/11/2008
Ethics approval number [1] 5974 0
NTX/08/07/060

Summary
Brief summary
This study builds on our previous work looking at how the body “processes” cancer drugs. Many drugs are metabolised in the liver by enzymes of the cytochrome P450 family. The level of enzyme activity varies from person to person. This is important, as poor metabolism of some drugs may put some people at greater risk of side effects, while extensive metabolism may mean the drug does not work as well. Cyclophosphamide is an important anticancer drug that is metabolised by a liver enzyme called CYP2C19. About 3% of Caucasian populations are genetically poor metabolisers for CYP2C19. Our recent work suggested that people may actually lose CYP2C19 metabolism simply through the fact of having cancer. It is possible to measure CYP2C19 activity in an individual by giving them a small dose of a test drug such as proguanil. In this study we plan to see how CYP2C19 metabolism changes (i) between people with different amounts of cancer in their body and (ii) in individual people with cancer as time goes on and their cancer changes. The knowledge gained from this study will help us in future as we try to better tailor cancer drug doses to the individual.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28966 0
Address 28966 0
Country 28966 0
Phone 28966 0
Fax 28966 0
Email 28966 0
Contact person for public queries
Name 12123 0
George Laking
Address 12123 0
Regional Cancer & Blood Services
Private Bag 92024
Auckland 1142
Country 12123 0
New Zealand
Phone 12123 0
+64 9 307 4949
Fax 12123 0
Email 12123 0
georgeL@adhb.govt.nz
Contact person for scientific queries
Name 3051 0
Nuala Helsby
Address 3051 0
Faculty of Medical & Health Sciences
University of Auckland
Private Bag 92019
Auckland 1023
Country 3051 0
New Zealand
Phone 3051 0
+64 9 923 9831
Fax 3051 0
Email 3051 0
n.helsby@auckland.ac.nz

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