Effect of liver metastases from gastrointestinal stromal tumour (GIST) on imatinib pharmacokinetics

Effect of liver metastases from gastrointestinal stromal tumour (GIST) on imatinib pharmacokinetics: an observational pharmacokinetic study

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

ISRCTN

Registry ID

ISRCTN63855172

Enrollment

Registered

2009-09-18

Start date

2004-09-01

Completion date

Unknown

Last updated

2015-01-13

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

Conditions

Gastrointestinal stromal tumour (GIST) Cancer Malignant neoplasm of other and ill-defined digestive organs

Interventions

Pharmacokinetic analysis: Pharmacokinetics of imatinib and its major metabolite CGP74588 will be assessed on the first day of imatinib administration and after 1 and 6 months and 1 year during the ima

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Histologically or cytologically confirmed diagnosis of GIST or CML 2. Indication for imatinib treatment 3. Aged greater than or equal to 18 years, either sex 4. Performance status (Karnofsky scale): 60 to 100 5. Written informed consent 6. Adequate haematological functions (absolute neutrophil count [ANC] greater than 1.5 x 10^9/L, platelets greater than 100 x 10^9/L) 7. Adequate renal functions (creatinine less than 120 µmol/L or calculated clearance [Cockroft method] greater than 65 mL/min) 8. Bilirubin less than 5 times upper limit of normal (UNL) 9. Complete work-up within 2 - 4 weeks prior to therapy

Exclusion criteria

Exclusion criteria: 1. Pregnant or lactating patients; patients must use adequate contraceptive if required 2. Patients pretreated with imatinib 3. Symptomatic central nervous system (CNS) metastases 4. Other serious illness or medical unstable condition requiring treatment or history of psychiatric disorder that would prohibit the understanding and giving of informed consent 5. Previous history of severe cardiovascular disease 6. Major surgery within the last 2 weeks before start of the protocol 7. Unwillingness to change medication, or no adequate alternatives available, when drugs, which are known to interact with liver CYP450 3A4/5 enzyme system, are taken

Design outcomes

Primary

Measure	Time frame
1. The change in imatinib PK parameters (mainly AUC) between month 1 and month 12 during imatinib administration in patients with liver metastases from GIST or without liver involvement in GIST or CML patients will be compared using a two-sample t-test or a Wilcoxon rank sum test if normality of observations cannot be confirmed 2. In an explorative analysis will be compared: 2.1. GIST patients with liver metastases that respond to imatinib with GIST patients with no change in burden of liver disease 2.2. The toxic side effects, especially oedema, skin rash, nausea/vomiting and myelosuppression with treatment with imatinib PK (t-test or Wilcoxon rank sum tests within each patient subset) 2.3. CYP3A4/5, CYP2D6, CYP2C9, MDR-1 and other relevant genetic polymorphisms, and haematological and non-haematological toxicity (t-test or Wilcoxon rank sum tests within each patient subset) with imatinib and its metabolite (CGP74588) pharmacokinetics in treated patients 2.4. The quantification of liver metastatic involvement will be considered with four levels: 2.4.1. Absence of liver involvement (level 0) 2.4.2. Less than 25% liver metastatic involvement (level 1) 2.4.3. 25 - 50% level (2) 2.4.4. More than 50% (level 3) for subsequent exploratory analyses 3. In the pharmacodynamics, the categorical variables considered (metastatic GIST, adjuvant GIST or CML, primary tumour or recurrence present, liver tumour burden, stomach lesions, GIST or CML histology, gastrointestinal origin of the disease, abdominal origin of the disease, prior surgery, prior radiotherapy, prior chemotherapy) will be evaluated using chi-square tests. The continuous variables considered (time since initial diagnosis of GIST or CML in days, white blood cell count, granulocytes, platelets, haemoglobin, creatinine, creatinine clearance (by Cockroft-Gault formula), bilirubin, SGOT, SGPT, albumin, alkaline phosphatase) will be evaluated using Student's t-tests. In patients with liver metastases, the liver tumour	—

Measure

Time frame

1. The change in imatinib PK parameters (mainly AUC) between month 1 and month 12 during imatinib administration in patients with liver metastases from GIST or without liver involvement in GIST or CML patients will be compared using a two-sample t-test or a Wilcoxon rank sum test if normality of observations cannot be confirmed 2. In an explorative analysis will be compared: 2.1. GIST patients with liver metastases that respond to imatinib with GIST patients with no change in burden of liver disease 2.2. The toxic side effects, especially oedema, skin rash, nausea/vomiting and myelosuppression with treatment with imatinib PK (t-test or Wilcoxon rank sum tests within each patient subset) 2.3. CYP3A4/5, CYP2D6, CYP2C9, MDR-1 and other relevant genetic polymorphisms, and haematological and non-haematological toxicity (t-test or Wilcoxon rank sum tests within each patient subset) with imatinib and its metabolite (CGP74588) pharmacokinetics in treated patients 2.4. The quantification of liver metastatic involvement will be considered with four levels: 2.4.1. Absence of liver involvement (level 0) 2.4.2. Less than 25% liver metastatic involvement (level 1) 2.4.3. 25 - 50% level (2) 2.4.4. More than 50% (level 3) for subsequent exploratory analyses 3. In the pharmacodynamics, the categorical variables considered (metastatic GIST, adjuvant GIST or CML, primary tumour or recurrence present, liver tumour burden, stomach lesions, GIST or CML histology, gastrointestinal origin of the disease, abdominal origin of the disease, prior surgery, prior radiotherapy, prior chemotherapy) will be evaluated using chi-square tests. The continuous variables considered (time since initial diagnosis of GIST or CML in days, white blood cell count, granulocytes, platelets, haemoglobin, creatinine, creatinine clearance (by Cockroft-Gault formula), bilirubin, SGOT, SGPT, albumin, alkaline phosphatase) will be evaluated using Student's t-tests. In patients with liver metastases, the liver tumour

—

Secondary

Measure	Time frame
1. Toxicity will be evaluated according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAEv3). The liver tumour lesions will be measured by computed tomography (CT). 2. The objective response to imatinib of liver metastases from GIST will be assessed according to the RECIST criteria	—

Countries

Italy, Netherlands

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Feb 4, 2026