Cytochrom p450 3A4 and 1A2 Phenotyping for the Individualization of Treatment With Sunitinib or Erlotinib in Cancer Patients
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.
It is well known that substantial interindividual variability of CYP3A4/1A2-phenotype activity is an important contributor to individual differences in the sensitivity to the frequently used tyrosine kinase inhibitors sunitinib and erlotinib. This study tests the potential for CYP-phenotyping to predict individual pharmacology and derive dosing algorithms for more tailored treatment of these drugs.
Condition or disease
Non Small-cell Lung CancerRenal-cell CancerGastrointestinal Stroma Tumor
Steady-state partial area-under the plasma concentration-time curve over 24 hours (AUC24h) of sunitinib and erlotinib and CYP3A4/1A2-phenotype activity as defined in the protocol [ Time Frame: 2 weeks ]
Sunitinib or erlotinib area under the concentration-time curve during 24 hours at steady-state conditions, compared with the CYP3A4 or CYP1A2 phenotype activity as assessed by the two probe drugs midazolam (CYP3A4) and/or caffeine (CYP1A2)
Secondary Outcome Measures :
Sunitinib and Erlotinib-associated toxicity according to the CTC criteria (v.3.0) [ Time Frame: 12 weeks (end of study) ]
Concentrations of Sunitinib, Erlotinib and probe drugs (Midazolam, Caffeine) in whole blood, sampled from patient's dried blood spots (DBS) [ Time Frame: 12 weeks (end of study) ]
Dried blood spots are a potential alternative to venous blood samples to assess drug exposure in cancer patients.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Layout table for eligibility information
Ages Eligible for Study:
18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Histologically or cytologically confirmed renal-cell cancer or gastrointestinal stromal tumor (for sunitinib) or non small-cell lung cancer (for erlotinib)
Both early or advanced tumor stage
Indication for the therapeutic use of either sunitinib or erlotinib
Written informed consent and willing to undergo PK-sampling
Patients > 18 years of age
ECOG performance status or ≤2
Adequate laboratory parameters:
i. Serum creatinine and serum bilirubin ≤ 1.5 X ULN ii. Serum ALT and AST ≤ 2.5 X ULN (or ≤ 5 in case of liver metastases) iii. Serum calcium ≤ 11,6 mg/dl (2.9 mmol/L)
Previous treatment with sunitinib or erlotinib
Known hypersensitivity to trial drug or any compounds of the drug
Concurrent systemic anticancer treatment with the exception of bisphosphonates and bevacizumab in patients with non small-cell lung cancer