Cytochrom p450 3A4 and 1A2 Phenotyping for the Individualization of Treatment With Sunitinib or Erlotinib in Cancer Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Cantonal Hospital of St. Gallen
Sponsor:
Collaborator:
University of Basel
Information provided by (Responsible Party):
Markus Joerger, Cantonal Hospital of St. Gallen
ClinicalTrials.gov Identifier:
NCT01402089
First received: July 20, 2011
Last updated: August 31, 2014
Last verified: August 2014
  Purpose

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

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Cantonal Hospital of St. Gallen:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: No ]
    Dried blood spots are a potential alternative to venous blood samples to assess drug exposure in cancer patients.


Estimated Enrollment: 60
Study Start Date: January 2012
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
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
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01402089

Contacts
Contact: Gabriela Kramer, MsC 714941111 ext +41 gabriela.kramer@kssg.ch

Locations
Switzerland
Cantonal Hospital St.Gallen Recruiting
St.Gallen, Switzerland, 9007
Contact: Markus Joerger, MD-PhD-ClinPharm    +41-76-559-10-70 ext 0041    markus.joerger@kssg.ch   
Principal Investigator: Markus Joerger, MD-PhD ClinPharm         
Sponsors and Collaborators
Markus Joerger
University of Basel
Investigators
Study Chair: Markus Joerger, MD PhD Cantonal Hospital St.Gallen (Switzerland)
  More Information

Additional Information:
No publications provided

Responsible Party: Markus Joerger, MD-PhD-ClinPharm, Cantonal Hospital of St. Gallen
ClinicalTrials.gov Identifier: NCT01402089     History of Changes
Other Study ID Numbers: SG 327/10
Study First Received: July 20, 2011
Last Updated: August 31, 2014
Health Authority: Switzerland: Swissmedic

Keywords provided by Cantonal Hospital of St. Gallen:
phenotyping
cytochrome p450
erlotinib
sunitinib
lung cancer
renal-cell cancer
gastrointestinal stromal tumor

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Renal Cell
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Erlotinib
Sunitinib
Midazolam
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014