- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01402089
Cytochrom p450 3A4 and 1A2 Phenotyping for the Individualization of Treatment With Sunitinib or Erlotinib in Cancer Patients
Study Overview
Status
Intervention / Treatment
Detailed Description
Objectives:
The primary objective of this study is to show that the individual CYP3A4 and CYP1A2-phenotype as assessed by probe drugs predicts drug exposure to sunitinib and erlotinib. Secondary objectives of the study are to define the correlation between the individual CYP-phenotype and treatment-related toxicity, testing the feasibility of drug bioanalysis from patient's dry blood spots (DBS), build an integrated covariate model on sunitinib and erlotinib pharmacokinetics and define a dosing algorithm for both sunitinib and erlotinib based on the individual CYP-phenotype.
Study endpoints:
Primary endpoint:
• To show that individual drug clearance of sunitinib or erlotinib is significantly higher in patients with a high-activity CYP3A4/1A2-phenotype.
Secondary endpoints:
- To specify the correlation between the CYP-phenotype and treatment-related toxicity.
- To assess the feasibility of drug bioanalysis from patient's dry blood spots (DBS).
- To build an integrated covariate model of sunitinib and erlotinib pharmacokinetics to define the quantitative relationship between the CYP-phenotype activity and drug exposure.
- To define a dosing algorithm for both sunitinib and erlotinib based on the individual CYP-phenotype using data simulations on the previously defined population covariate model.
Trial Design:
Prospective, nonrandomized, pharmacological cohort study.
Main selection criteria
- Histologically or cytologically confirmed renal-cell cancer (sunitinib), gastrointestinal stromal tumor (sunitinib) or non small-cell lung cancer (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
- Adequate organ function
- No concurrent radiotherapy or systemic anticancer treatment with another drug
Trial Duration The present study is projected to start in June 2011, with the inclusion of a total of 60 patients (at least 25 patients for each sunitinib and erlotinib). The study is expected to finalize patient accrual in December 2013.
Statistical considerations The trial is designed to show a linear inverse relationship between the individual CYP-phenotype and total drug steady-state AUC (sunitinib plus SU12662 and erlotinib plus OSI-420, respectively), whereat CYP1A2 only accounts for the metabolism of erlotinib. With the inclusion of 60 patients, the study has a power of 90% to detect a relevant relationship between the CYP-phenotype activity and sunitinib/erlotinib steady-state AUC, with a regression coefficient of >0.4 for the H1-hypothesis (and accepting a regression coefficient of >0.1 for the H0-hypothesis) at the 5% significance level.
Trial Treatment Sunitinib: 50 mg p.o. daily for 4 out of 6 weeks, or 37.5 mg daily continuous until disease progression, unacceptable toxicity or withdrawal of informed consent.
Erlotinib: 150 mg p.o. daily until disease progression, unacceptable toxicity or withdrawal of informed consent.
Potential study outcome This study makes a significant contribution to global efforts for more individualized anticancer treatment. If successful, we will be able to make dosing recommendations for sunitinib and erlotinib based on a simple probe drug assay.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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-
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St.Gallen, Switzerland, 9007
- Cantonal Hospital St.Gallen
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
2 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sunitinib and Erlotinib-associated toxicity according to the CTC criteria (v.3.0)
Time Frame: 12 weeks (end of study)
|
12 weeks (end of study)
|
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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.
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12 weeks (end of study)
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Kidney Neoplasms
- Neoplasms, Connective Tissue
- Carcinoma, Renal Cell
- Gastrointestinal Stromal Tumors
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Enzyme Inhibitors
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Purinergic Antagonists
- Purinergic Agents
- Antineoplastic Agents
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Tranquilizing Agents
- Psychotropic Drugs
- Protein Kinase Inhibitors
- Hypnotics and Sedatives
- Adjuvants, Anesthesia
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Phosphodiesterase Inhibitors
- Purinergic P1 Receptor Antagonists
- Central Nervous System Stimulants
- Erlotinib Hydrochloride
- Midazolam
- Sunitinib
- Caffeine
Other Study ID Numbers
- SG 327/10
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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