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.

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12609000056291

Enrollment

Registered

2009-01-23

Start date

2009-04-14

Completion date

2012-12-31

Last updated

2024-12-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

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.

Interventions

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.

Study design

Allocation

Non-randomised trial

Intervention model

Single group

Primary purpose

Treatment

Masking

Open (masking not used)

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Healthy volunteers

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

Exclusion criteria

Patients receiving medication which is either a CYP2C19 inhibitor or inducer, and where a washout period is not clinically feasible

Outcome results