Non Small-cell Lung CancerPhase 4NCT01402089
Cytochrom p450 3A4 and 1A2 Phenotyping for the Individualization of Treatment With Sunitinib or Erlotinib in Cancer Patients
A Phase 4 study testing Sunitinib, Erlotinib and Midazolam in people with Non Small-cell Lung Cancer and Renal-cell Cancer, run by Markus Joerger at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small-cell Lung Cancer, Renal-cell Cancer, Gastrointestinal Stroma Tumor
- What is being tested?
- Sunitinib, Erlotinib and Midazolam
- Type of treatment
- Pill or oral medicine
- How many people
- 54 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jan 2012to Nov 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Keywords
- phenotyping, cytochrome p450, erlotinib, sunitinib, lung cancer, renal-cell cancer, gastrointestinal stromal tumor
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Gastrointestinal Stromal Tumors, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
Also called Sutent
Patients with renal-cell cancer or GIST are receiving conventional treatment with sunitinib (50mg/day for 4 out of 6 weeks)
ErlotinibDrug
Also called Tarceva
Patients with non small-cell lung cancer receive conventional treatment with erlotinib 150mg/day.
MidazolamDrug
Also called Midazolam drinking solution
For phenotyping of CYP3A4, all patients receive one-time midazolam 2mg as a drinking solution at the start of study treatment.
CaffeineDrug
Also called Coffeinum N 0.2g
For phenotyping of CYP1A2, patients with non small-cell lung cancer receive additionally one-time caffeine 100mg as a tablet.
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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)
Measured: 2 weeks
Secondary outcomes (2)
Sunitinib and Erlotinib-associated toxicity according to the CTC criteria (v.3.0)
Measured: 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)
Dried blood spots are a potential alternative to venous blood samples to assess drug exposure in cancer patients.
Measured: 12 weeks (end of study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2011 (estimated)
- Study startJan 2012
- Primary completionJul 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small-cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Markus Joerger
- Sponsor type
- University, hospital or other
- Collaborators
- University of Basel
- Responsible party
- Sponsor-investigator, Markus Joerger, Cantonal Hospital of St. Gallen
- Investigators
- Markus Joerger, MD PhD, Study chair, Cantonal Hospital of St. Gallen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01402089
- Sponsor's protocol ID
- SG 327/10
- Status last verified
- Jan 2016
- First submitted
- 20 Jul 2011
- Last updated
- 2 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cytochrom p450 3A4 and 1A2 Phenotyping for the Individualization of Treatment With Sunitinib or Erlotinib in Cancer Patients
- ClinicalTrials.gov ID
- NCT01402089
- Acronym / sponsor ID
- SG 327/10
- Keywords
- phenotyping, cytochrome p450, erlotinib, sunitinib, lung cancer, renal-cell cancer, gastrointestinal stromal tumor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Markus JoergerUniversity, hospital or other
- Collaborators
- University of Basel
- Study start
- Jan 2012
- Primary completion
- Jul 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 26 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SunitinibAlso: SutentPatients with renal-cell cancer or GIST are receiving conventional treatment with sunitinib (50mg/day for 4 out of 6 weeks) | Drug | – |
| ErlotinibAlso: TarcevaPatients with non small-cell lung cancer receive conventional treatment with erlotinib 150mg/day. | Drug | – |
| MidazolamAlso: Midazolam drinking solutionFor phenotyping of CYP3A4, all patients receive one-time midazolam 2mg as a drinking solution at the start of study treatment. | Drug | – |
| CaffeineAlso: Coffeinum N 0.2gFor phenotyping of CYP1A2, patients with non small-cell lung cancer receive additionally one-time caffeine 100mg as a tablet. | Drug | – |
Primary outcome
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 secondary outcomes
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Markus Joerger, MD PhD study chair
Cantonal Hospital of St. Gallen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sunitinib, Erlotinib and Midazolam in people with Non Small-cell Lung Cancer and Renal-cell Cancer, run by Markus Joerger at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2016.