Sunitinib and Erlotinib and Midazolam in Non Small-cell Lung Cancer and Renal-cell Cancer and Gastrointestinal Stroma Tumor - Clinical Trials Registry

Study Overview

Status

Completed

Conditions

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

Interventional

Enrollment (Actual)

54

Phase

Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Switzerland
- - St.Gallen, Switzerland, 9007
    - Cantonal Hospital St.Gallen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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)
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.	12 weeks (end of study)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Markus Joerger

Collaborators

University of Basel

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Institute research homepage

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2012

Primary Completion (Actual)

July 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

July 20, 2011

First Submitted That Met QC Criteria

July 25, 2011

First Posted (Estimate)

July 26, 2011

Study Record Updates

Last Update Posted (Estimate)

February 2, 2016

Last Update Submitted That Met QC Criteria

January 31, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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.

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