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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. Identifier: NCT01402089
Recruitment Status : Completed
First Posted : July 26, 2011
Last Update Posted : February 2, 2016
University of Basel
Information provided by (Responsible Party):
Markus Joerger, Cantonal Hospital of St. Gallen

Brief Summary:
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 Intervention/treatment Phase
Non Small-cell Lung Cancer Renal-cell Cancer Gastrointestinal Stroma Tumor Drug: Sunitinib Drug: Erlotinib Drug: Midazolam Drug: Caffeine Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cytochrom p450 3A4 and 1A2 Phenotyping for the Individualization of Treatment With Sunitinib or Erlotinib in Cancer Patients
Study Start Date : January 2012
Actual Primary Completion Date : July 2015
Actual Study Completion Date : November 2015

Intervention Details:
  • Drug: Sunitinib
    Patients with renal-cell cancer or GIST are receiving conventional treatment with sunitinib (50mg/day for 4 out of 6 weeks)
    Other Name: Sutent
  • Drug: Erlotinib
    Patients with non small-cell lung cancer receive conventional treatment with erlotinib 150mg/day.
    Other Name: Tarceva
  • Drug: Midazolam
    For phenotyping of CYP3A4, all patients receive one-time midazolam 2mg as a drinking solution at the start of study treatment.
    Other Name: Midazolam drinking solution
  • Drug: Caffeine
    For phenotyping of CYP1A2, patients with non small-cell lung cancer receive additionally one-time caffeine 100mg as a tablet.
    Other Name: Coffeinum N 0.2g

Primary Outcome Measures :
  1. 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 :
  1. Sunitinib and Erlotinib-associated toxicity according to the CTC criteria (v.3.0) [ Time Frame: 12 weeks (end of study) ]
  2. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • Previous treatment with sunitinib or erlotinib
  • Known hypersensitivity to trial drug or any compounds of the drug
  • Concurrent radiotherapy
  • Concurrent systemic anticancer treatment with the exception of bisphosphonates and bevacizumab in patients with non small-cell lung cancer

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01402089

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Cantonal Hospital St.Gallen
St.Gallen, Switzerland, 9007
Sponsors and Collaborators
Markus Joerger
University of Basel
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Study Chair: Markus Joerger, MD PhD Cantonal Hospital St. Gallen, Switzerland

Additional Information:
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Responsible Party: Markus Joerger, MD-PhD-ClinPharm, Cantonal Hospital of St. Gallen Identifier: NCT01402089     History of Changes
Other Study ID Numbers: SG 327/10
First Posted: July 26, 2011    Key Record Dates
Last Update Posted: February 2, 2016
Last Verified: January 2016

Keywords provided by Markus Joerger, Cantonal Hospital of St. Gallen:
cytochrome p450
lung cancer
renal-cell cancer
gastrointestinal stromal tumor

Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Gastrointestinal Stromal Tumors
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Erlotinib Hydrochloride