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Trial registered on ANZCTR


Registration number
ACTRN12612001170819
Ethics application status
Approved
Date submitted
31/10/2012
Date registered
6/11/2012
Date last updated
7/11/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Observational study of frequency and causes of impaired liver metabolism of cyclophosphamide in breast cancer
Scientific title
Observational study of frequency and causes of impaired liver metabolism of cyclophosphamide in breast cancer
Secondary ID [1] 281477 0
None
Universal Trial Number (UTN)
Trial acronym
The LIME Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 287737 0
Condition category
Condition code
Cancer 288078 288078 0 0
Breast

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Participant patients will be dispensed with a 200 mg dose of the probe drug, proguanil on two separate occasions. The patients will be requested to take two tablets containing 100 mg each, by mouth three hours before the commencement of chemotherapy. The patients will also be requested to take two tablets containing 100 mg each, by mouth three hours prior to the commencement of the 3rd cycle of chemotherapy.
The duration between the 1st and 3rd cycles of chemotherapy will be dependent on the patients own chemotherapy schedules.
Intervention code [1] 285981 0
Not applicable
Comparator / control treatment
There is no comparator or control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 288284 0
To elucidate whether compromised CYP2C19 activity occurs in women with breast cancer at 3 hours post administration of proguanil. CYP2C19 functional activity will be measured by plasma samples at 3 hours post administration of proguanil and at 3 hours and 15 minutes post administration of proguanil.
Timepoint [1] 288284 0
At 3 hours post administration of proguanil and at 3 hours and 15 minutes post administration of proguanil. The plasma samples will be taken prior to the patients routine 1st and 3rd cycle of chemotherapy.
Primary outcome [2] 288285 0
To elucidate whether compromised CYP2C19 activity results in decreased activation of cyclophosphamide in women with breast cancer. CYP2C19 functional activity will be measured by plasma samples at 15 minutes and 30 minutes following the completion of the 1st cycle of the cyclophosphamide infusion and the 3rd cycle of the cyclophosphamide infusion.
Timepoint [2] 288285 0
At 15 minutes and 30 minutes following the completion of the 1st cycle of the cyclophosphamide infusion. At 15 minutes and 30 minutes following the completion the 3rd cycle of the cyclophosphamide infusion.
Secondary outcome [1] 299761 0
To elucidate whether there is a relationship between compromised CYP2C19 and pro-inflammatory mediators, such as cytokines in women with breast cancer as measured by plasma samples.
Timepoint [1] 299761 0
At 30 minutes following the completion of the 1st cycle of the cyclophosphamide infusion. At 30 minutes following the completion the 3rd cycle of the cyclophosphamide infusion.
Secondary outcome [2] 299762 0
To elucidate whether a combination of genetic (i.e. CYP2C19/CYP2B6) and additional non-genetic factors, such as markers of inflammation, influence the metabolism of cyclophosphamide in women with breast cancer as measured from plasma samples.
Timepoint [2] 299762 0
All patients will have blood collected at baseline for determination of CYP2C19 genotype.

Eligibility
Key inclusion criteria
Age>18
ECOG (Eastern Cooperative Oncology Group) Performance Status 0-2
Histologically confirmed breast cancer
To receive intravenous cyclophosphamide as part of adjuvant, neoadjuvant or first line chemotherapy for breast cancer as part of standard care.
Staging investigations in process (should not be greater than 2 weeks after start of chemotherapy).
Patients must be able to provide written informed consent
Aspartate transaminase (AST), Alaninine transaminase (ALT) =< 2.5 X upper limit of normal (ULN) for institution
Alkaline phosphatase <5x ULN
Bilirubin =< ULN, except when due to Gilbert’s Disease
Creatinine <1.5 ULN
Minimum age
19 Years
Maximum age
No limit
Gender
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 of 5 days is not clinically feasible
Chronic inflammatory condition such as systemic lupus erythematosis, inflammatory bowel disease, other autoimmune phenomenon or active chronic infection
Active infections (e.g. wound) at time of chemotherapy
Pregnant or breast feeding
Other active malignancy within the last 5 years, excluding non-melanoma skin cancers, or preinvasive cervical cancer that has been treated definitively

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis

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 outside Australia
Country [1] 4662 0
New Zealand
State/province [1] 4662 0

Funding & Sponsors
Funding source category [1] 286246 0
Charities/Societies/Foundations
Name [1] 286246 0
Genesis Oncology Trust
Address [1] 286246 0
Genesis Oncology Trust
PO Box 17188
Greenlane
Auckland 1546
Country [1] 286246 0
New Zealand
Funding source category [2] 286247 0
Charities/Societies/Foundations
Name [2] 286247 0
Cancer Society of New Zealand
Address [2] 286247 0
Cancer Society of New Zealand
PO Box 12700
Wellington 6144
Country [2] 286247 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Faculty of Medical and Health Sciences,
University of Auckland,
85 Park Road
Grafton
Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 285050 0
Hospital
Name [1] 285050 0
Auckland District Health Board
Address [1] 285050 0
Private Bag 92189
Auckland Mail Centre
Auckland 1142
Country [1] 285050 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288324 0
Northern A Committee
Ethics committee address [1] 288324 0
Health and Disability Ethics Committees
1 the Terrace
PO Box 5013
Wellington 6011
Ethics committee country [1] 288324 0
New Zealand
Date submitted for ethics approval [1] 288324 0
Approval date [1] 288324 0
02/08/2012
Ethics approval number [1] 288324 0
NTX/12/06/052

Summary
Brief summary
Evidence suggests that that cancer may affect the activity of a liver enzyme (CYP2C19) that helps to activate the anticancer drug cyclophosphamide, an important agent in the treatment of breast cancer.
There are large differences in the way each person responds to anticancer drugs. Some of these differences relate to the way the body processes drugs using enzymes found in the liver. One reason for different reactions to cancer treatment may be differences in amounts of these liver enzymes or differences in the way they work. The liver enzyme that we are studying is called CYP2C19. Most of the activity of CYP2C19 is inherited. CYP2C19 can activate cyclophosphamide, a drug used in your treatment. Our recent work suggested that in the activity of this CYP2C19 gene is regulated differently in cancer patients than in healthy people, so that some cancer patients may have extremely low drug processing activity.
It is possible to measure CYP2C19 activity by giving them a small dose of a drug called proguanil. This medication is often taken by travellers for prevention of malaria and is processed by the body in a similar way to cyclophosphamide.
In this study we would like to measure the activity of this CYP2C19 enzyme by measuring proguanil blood concentrations after a test dose and also directly measure the activation of cyclophosphamide in blood samples.
By learning more about the things that influence a person’s ability to process drugs, we might be better able in the future to fine-tune the dose of cancer drugs to the individual.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34900 0
Address 34900 0
Country 34900 0
Phone 34900 0
Fax 34900 0
Email 34900 0
Contact person for public queries
Name 18147 0
Dr Nuala Helsby
Address 18147 0
Molecular Medicine and Pathology
Faculty of Medical and Health Sciences,
University of Auckland,
85 Park Road
Grafton
Auckland 1023
Country 18147 0
New Zealand
Phone 18147 0
+64 9 923 9831
Fax 18147 0
Email 18147 0
n.helsby@auckland.ac.nz
Contact person for scientific queries
Name 9075 0
Dr Nuala Helsby
Address 9075 0
Molecular Medicine and Pathology
Faculty of Medical and Health Sciences,
University of Auckland,
85 Park Road
Grafton
Auckland 1023
Country 9075 0
New Zealand
Phone 9075 0
+64 9 923 9831
Fax 9075 0
Email 9075 0
n.helsby@auckland.ac.nz

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