CancerPhase 1NCT01548170
To Assess the Interaction Between Sunitinib and Ketoconazole to Reduce the Dose and Cost of Sunitinib
A Phase 1 study testing Sunitinib, Sunitinib and Ketoconazol and Sunitiinb and Ketoconazol in people with Cancer, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
Trial summary
Sunitinib is an ATP competitive tyrosine kinase inhibitor of several membrane receptors including VEGFR-1, -2, and -3, PDGFR-α and -β, c-KIT, CSF-1R, FLT-3, and RET. Through this molecular mode of action, sunitinib is able to avoid tumoral angiogenesis and proliferation. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Cancer
- What is being tested?
- Sunitinib, Sunitinib and Ketoconazol and Sunitiinb and Ketoconazol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteSpain
- Study dates
- Apr 2011to Jul 2011
- Phase
- Phase 1
- 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 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy individuals men who give their written consent to participate in the study, after having received information about the design, the project objectives, the risks and that at any moment they can refuse their cooperation.
- Age between 18 and 35 years.
- Subjects with a BMI that is between 19 and 28.
- Healthy subjects, without any organic or psychological pathology.
- Clinical history and physical examination within normal limits.
- Lack of clinically relevant abnormalities in blood test (hematology, biochemistry, virology) and urine test
- Vital signs and electrocardiographic recording in the normal range.
Who cannot join
- Subjects suffering from organic or psychological pathology. Prior to the inclusion of any volunteer it should be considered all security parameters mentioned in the protocol (biochemical markers of kidney damage and / or liver out of the normal range set by the laboratory).
- Subjects who have received prescription drug treatment in the last 15 days or any medication within 48 hours before receiving study medication.
- Known hypersensitivity to any drug
- Suspected of drug abuse
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Pilot, Dose Finding Clinical Trial to Assess the Interaction Between Sunitinib and Ketoconazole to Reduce the Dose and Cost of Sunitinib for National Health System
Sunitinib is an ATP competitive tyrosine kinase inhibitor of several membrane receptors including VEGFR-1, -2, and -3, PDGFR-α and -β, c-KIT, CSF-1R, FLT-3, and RET. Through this molecular mode of action, sunitinib is able to avoid tumoral angiogenesis and proliferation. Sunitinib is already approved by the FDA, EMEA and AEMPS for the treatment of patients with metastatic renal cell carcinomas and those with metastatic gastrointestinal stromal tumors (GIST) with progression or intolerance to imatinib.
Suntinib has recently reported to be superior than placebo in terms of response rate (9.3% vs. 0%; p<0.05), progression free survival (11.4 vs. 5,5 months; HR 0.41;p<0.05), and overall survival (HR 0.40;p<0.05) when administered in a phase 3 trial to patients with advanced pancreatic neuroendocrine tumors (NETs).
Read more
Sunitinib is an expensive drug that drains the budget of health public system therefore it demands a rational drug use.
Sunitinib is metabolized by CYP3A4, that belongs to the P450 cytochrome system in the liver. Most of the drug is eliminated in faeces and only 16% by urine. Sunitinib has no food-effect when taken with meals. Pharmacokinetics parameters did not differ between cancer patients and healthy volunteers.
Houk et al. Showed that the area under the curve of plasmatic concentration of sunitinib and its active metabolite did correlate with clinical outcome. In other words, the higher plasma concentration area under the curve the highest rates of radiological response, progression free and overall survival rates.
Ketoconazol is an antifungal drug that inhibits the CY3A4 inducing an elevation of peak plasma levels of other drugs administered simultaneously and that are metabolized by the same system. In the labeling sheet of sunitinib it is said that ketoconazol induced a 49% and 51% of increase of plasmatic sunitinib Cmax y AUC0-∞ when both drugs were administered together. This fact makes that the investigatorspropose that by administering both drugs simultaneously the investigators could reduce sunitinib dose by a lower metabolization with similar plasma concentration. The dose reduction would impact in drug cost.
Here the investigators propose to determine the most optimal combination dose of sunitinib (25 mg or 37.5 mg) and ketoconazol (200mg o 400mg) by which the investigators could have plasmatic bioequivalent concentrations compared with single dose of sunitinib 50mg.
Each volunteer will be assigned to a treatment arm (Arm A and Arm B). Volunteers included in Arm A will take: sunitinib 50 mg, sunitinib 37.5 mg + ketoconazole 200 mg and sunitinib 37.5 mg + 400 mg ketoconazole. Volunteers included in Arm B will take: sunitinib 50 mg, sunitinib 25 mg + ketoconazole 200 mg and sunitinib 25 mg + 400 mg ketoconazole
Read the detailed description
This is a phase I, pilot, open, randomized, parallel, and cross-over trial to assess the interaction between three different dose levels of sunitinib (50 mg, 37.5 mg, and 25 mg) and two dose levels of ketoconazole (200 mg and 400 mg) in 12 healthy volunteers (6 voluunteers in each group of treatment) Each volunteer will be assigned to a treatment arm (Arm A and Arm B. Volunteers included in Arm A will take: sunitinib 50 mg, sunitinib 37.5 mg + ketoconazole 200 mg and sunitinib 37.5 mg + 400 mg ketoconazole. Volunteers included in Arm B will take: sunitinib 50 mg, sunitinib 25 mg + ketoconazole 200 mg and sunitinib 25 mg + 400 mg ketoconazole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
One capsule of sunitinib 50 mg orally. Single dose
Sunitinib and KetoconazolDrug
Sunitinib capsule 37.5mg. Single dose Ketoconazol 2 tablets of 200mg administered daily during 6 days.
Sunitiinb and KetoconazolDrug
Sunitinib capsule 37.5mg. Single dose Ketoconazol 1 tablet of 200mg administered daily during 6 days.
Sunitinib and KetoconazolDrug
Sunitinib capsule 25mg. Single dose Ketoconazol 1 tablet of 200mg administered daily during 6 days.
Sunitinib and KetoconazolDrug
Sunitinib capsule 25mg. Single dose Ketoconazol 2 tablets of 200mg administered daily during 6 days.
| Study group | Role | What they receive |
|---|---|---|
| Sunitinib 50mg | Active comparator | Sunitinib 50 mg administered as a single dose. Receives: Drug: Sunitinib |
| Sunitinib 37.5mg + Ketoconazol 200mg | Experimental | The drugs will be administered as follows:
* Sunitinib 37.5mg oral single dose.
* Ketoconazole 200 mg orally, once daily for 6 days. (Combination with sunitinib will be performed on day 4) Receives: Drug: Sunitiinb and Ketoconazol |
| Sunitinib 37.5 mg + Ketoconazol 400 mg | Experimental | The drugs will be administered as follows:
* Sunitinib 37.5mg oral single dose.
* Ketoconazole 400 mg orally, once daily for 6 days. (Combination with sunitinib will be performed on day 4) Receives: Drug: Sunitinib and Ketoconazol |
| Sunitinib 25mg + Ketoconazol 200mg | Experimental | The drugs will be administered as follows:
* Sunitinib 25mg oral single dose.
* Ketoconazole 200 mg orally, once daily for 6 days. (Combination with sunitinib will be performed on day 4) Receives: Drug: Sunitinib and Ketoconazol |
| Sunitinib 25mg + Ketoconazol 400mg | Experimental | The drugs will be administered as follows:
* Sunitinib 25mg oral single dose.
* Ketoconazole 400 mg orally, once daily for 6 days. (Combination with sunitinib will be performed on day 4) Receives: Drug: Sunitinib and Ketoconazol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sunitinib pharmacokinetic parameters (Maximum plasma concentration (Cmax) and Area under the plasma concentration curve (AUC0-72) obtained in the different treatment groups.
On the fourth day of each period patient will be hospitalized in the clinical trial unit in order to obtain plasma concentrations previous to the administration of the corresponding dose and at the following times port-administration: 2h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 11h, 12h, 14h, 16h, 24h, 36h, 48h amd 72h. These measures will be calculated in order to describe the pharmacokinetic profile of each treatment arm.
Measured: Up to 72 hours postdose for each period
Secondary outcomes (4)
Other Sunitinib pharmacokinetic parameters (first time to reach Cmax (tmax) and Area under the plasma concentration curve (AUC0-Inf) obtained in the different treatment groups.
On the fourth day of each period patient will be hospitalized in the clinical trial unit in order to obtain plasma concentrations previous to the administration of the corresponding dose and at the following times port-administration: 2h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 11h, 12h, 14h, 16h, 24h, 36h, 48h amd 72h. These measures will be calculated in order to describe the pharmacokinetic profile of each treatment arm.
Measured: Up to 72 hours postdose for each period
Coefficient of variation of AUC and Cmax
To estimate the actual coefficient of variation of AUC and Cmax of sunitinib in our environment when given alone and in combination with ketoconazole.
Measured: 9 months
Change in QT interval
An ECG to measure the QT interval will be performed coinciding with blood samples taken basal and at 6h, 8h, 10h, 12h and 72 h after drug administration in each period.
Measured: On day 4 of each period
Adverse events reported
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2012 (estimated)
- Study startApr 2011
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Enrique Grande Pulido, Principal investigator, Hospital Universitario Ramon y Cajal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01548170
- Sponsor's protocol ID
- KS-ONCOFARMA-01
- Other IDs
- 2010-023739-41
- Status last verified
- Mar 2012
- First submitted
- 23 Dec 2011
- Last updated
- 8 Mar 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Pilot, Dose Finding Clinical Trial to Assess the Interaction Between Sunitinib and Ketoconazole to Reduce the Dose and Cost of Sunitinib for National Health System
- ClinicalTrials.gov ID
- NCT01548170
- Acronym / sponsor ID
- KS-ONCOFARMA-01
- Conditions
- Cancer
- Keywords
- Pharmacokinetic, Sunitinib, Ketoconazol, interaction, Phase I
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y CajalUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 8 Mar 2012 (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.
Sunitinib is an ATP competitive tyrosine kinase inhibitor of several membrane receptors including VEGFR-1, -2, and -3, PDGFR-α and -β, c-KIT, CSF-1R, FLT-3, and RET. Through this molecular mode of action, sunitinib is able to avoid tumoral angiogenesis and proliferation. Sunitinib is already approved by the FDA, EMEA and AEMPS for the treatment of patients with metastatic renal cell carcinomas and those with metastatic gastrointestinal stromal tumors (GIST) with progression or intolerance to imatinib.
Suntinib has recently reported to be superior than placebo in terms of response rate (9.3% vs. 0%; p<0.05), progression free survival (11.4 vs. 5,5 months; HR 0.41;p<0.05), and overall survival (HR 0.40;p<0.05) when administered in a phase 3 trial to patients with advanced pancreatic neuroendocrine tumors (NETs).
Sunitinib is an expensive drug that drains the budget of health public system therefore it demands a rational drug use.
Sunitinib is metabolized by CYP3A4, that belongs to the P450 cytochrome system in the liver. Most of the drug is eliminated in faeces and only 16% by urine. Sunitinib has no food-effect when taken with meals. Pharmacokinetics parameters did not differ between cancer patients and healthy volunteers.
Houk et al. Showed that the area under the curve of plasmatic concentration of sunitinib and its active metabolite did correlate with clinical outcome. In other words, the higher plasma concentration area under the curve the highest rates of radiological response, progression free and overall survival rates.
Ketoconazol is an antifungal drug that inhibits the CY3A4 inducing an elevation of peak plasma levels of other drugs administered simultaneously and that are metabolized by the same system. In the labeling sheet of sunitinib it is said that ketoconazol induced a 49% and 51% of increase of plasmatic sunitinib Cmax y AUC0-∞ when both drugs were administered together. This fact makes that the investigatorspropose that by administering both drugs simultaneously the investigators could reduce sunitinib dose by a lower metabolization with similar plasma concentration. The dose reduction would impact in drug cost.
Here the investigators propose to determine the most optimal combination dose of sunitinib (25 mg or 37.5 mg) and ketoconazol (200mg o 400mg) by which the investigators could have plasmatic bioequivalent concentrations compared with single dose of sunitinib 50mg.
Each volunteer will be assigned to a treatment arm (Arm A and Arm B). Volunteers included in Arm A will take: sunitinib 50 mg, sunitinib 37.5 mg + ketoconazole 200 mg and sunitinib 37.5 mg + 400 mg ketoconazole. Volunteers included in Arm B will take: sunitinib 50 mg, sunitinib 25 mg + ketoconazole 200 mg and sunitinib 25 mg + 400 mg ketoconazole
Detailed description
This is a phase I, pilot, open, randomized, parallel, and cross-over trial to assess the interaction between three different dose levels of sunitinib (50 mg, 37.5 mg, and 25 mg) and two dose levels of ketoconazole (200 mg and 400 mg) in 12 healthy volunteers (6 voluunteers in each group of treatment) Each volunteer will be assigned to a treatment arm (Arm A and Arm B. Volunteers included in Arm A will take: sunitinib 50 mg, sunitinib 37.5 mg + ketoconazole 200 mg and sunitinib 37.5 mg + 400 mg ketoconazole. Volunteers included in Arm B will take: sunitinib 50 mg, sunitinib 25 mg + ketoconazole 200 mg and sunitinib 25 mg + 400 mg ketoconazole
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Sunitinib 50mg | Active comparator | Drug: SunitinibSunitinib 50 mg administered as a single dose. |
| Sunitinib 37.5mg + Ketoconazol 200mg | Experimental | Drug: Sunitiinb and KetoconazolThe drugs will be administered as follows: * Sunitinib 37.5mg oral single dose. * Ketoconazole 200 mg orally, once daily for 6 days. (Combination with sunitinib will be performed on day 4) |
| Sunitinib 37.5 mg + Ketoconazol 400 mg | Experimental | Drug: Sunitinib and KetoconazolThe drugs will be administered as follows: * Sunitinib 37.5mg oral single dose. * Ketoconazole 400 mg orally, once daily for 6 days. (Combination with sunitinib will be performed on day 4) |
| Sunitinib 25mg + Ketoconazol 200mg | Experimental | Drug: Sunitinib and KetoconazolThe drugs will be administered as follows: * Sunitinib 25mg oral single dose. * Ketoconazole 200 mg orally, once daily for 6 days. (Combination with sunitinib will be performed on day 4) |
| Sunitinib 25mg + Ketoconazol 400mg | Experimental | Drug: Sunitinib and KetoconazolThe drugs will be administered as follows: * Sunitinib 25mg oral single dose. * Ketoconazole 400 mg orally, once daily for 6 days. (Combination with sunitinib will be performed on day 4) |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Healthy individuals men who give their written consent to participate in the study, after having received information about the design, the project objectives, the risks and that at any moment they can refuse their cooperation.
- Age between 18 and 35 years.
- Subjects with a BMI that is between 19 and 28.
- Healthy subjects, without any organic or psychological pathology.
- Clinical history and physical examination within normal limits.
Key exclusion criteria (4 listed)
- Subjects suffering from organic or psychological pathology. Prior to the inclusion of any volunteer it should be considered all security parameters mentioned in the protocol (biochemical markers of kidney damage and / or liver out of the normal range set by the laboratory).
- Subjects who have received prescription drug treatment in the last 15 days or any medication within 48 hours before receiving study medication.
- Known hypersensitivity to any drug
- Suspected of drug abuse
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 |
|---|---|---|
| SunitinibOne capsule of sunitinib 50 mg orally. Single dose | Drug | Sunitinib 50mg |
| Sunitinib and KetoconazolSunitinib capsule 37.5mg. Single dose Ketoconazol 2 tablets of 200mg administered daily during 6 days. | Drug | Sunitinib 37.5 mg + Ketoconazol 400 mg |
| Sunitiinb and KetoconazolSunitinib capsule 37.5mg. Single dose Ketoconazol 1 tablet of 200mg administered daily during 6 days. | Drug | Sunitinib 37.5mg + Ketoconazol 200mg |
| Sunitinib and KetoconazolSunitinib capsule 25mg. Single dose Ketoconazol 1 tablet of 200mg administered daily during 6 days. | Drug | Sunitinib 25mg + Ketoconazol 200mg |
| Sunitinib and KetoconazolSunitinib capsule 25mg. Single dose Ketoconazol 2 tablets of 200mg administered daily during 6 days. | Drug | Sunitinib 25mg + Ketoconazol 400mg |
Primary outcome
Sunitinib pharmacokinetic parameters (Maximum plasma concentration (Cmax) and Area under the plasma concentration curve (AUC0-72) obtained in the different treatment groups.
Time frame: Up to 72 hours postdose for each period
On the fourth day of each period patient will be hospitalized in the clinical trial unit in order to obtain plasma concentrations previous to the administration of the corresponding dose and at the following times port-administration: 2h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 11h, 12h, 14h, 16h, 24h, 36h, 48h amd 72h. These measures will be calculated in order to describe the pharmacokinetic profile of each treatment arm.
4 secondary outcomes
Other Sunitinib pharmacokinetic parameters (first time to reach Cmax (tmax) and Area under the plasma concentration curve (AUC0-Inf) obtained in the different treatment groups.
Time frame: Up to 72 hours postdose for each period
Coefficient of variation of AUC and Cmax
Time frame: 9 months
Change in QT interval
Time frame: On day 4 of each period
Adverse events reported
Time frame: 9 months
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 8 Mar 2012.
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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.
Enrique Grande Pulido principal investigator
Hospital Universitario Ramon y Cajal
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sunitinib, Sunitinib and Ketoconazol and Sunitiinb and Ketoconazol in people with Cancer, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
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 7 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 8 Mar 2012. 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 Spain. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Sunitinib pharmacokinetic parameters (Maximum plasma concentration (Cmax) and Area under the plasma concentration curve (AUC0-72) obtained in the different treatment groups. (time frame: Up to 72 hours postdose for each period). 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 8 Mar 2012.