Solid TumorsPhase 2NCT00697437
Effect of Ketoconazole Inhibition of CYP3A on Urinary Excretion of Docetaxel
A Phase 2 study testing Docetaxel and Ketoconazole in people with Solid Tumors, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
Primary Objective: To confirm if ketoconazole inhibition of CYP3A activity affects fractional excretion of docetaxel in the urine. Secondary Objective: To compare the metabolite ratios of the major metabolites of docetaxel in the presence and absence of CYP3A inhibition. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- Docetaxel and Ketoconazole
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteSingapore
- Study dates
- Oct 2006to Oct 2013
- Phase
- Phase 2
- 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
- Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which docetaxel is indicated.
- Patients must have measurable or evaluable disease.
- With the exception of alopecia, fatigue, nausea and asthenia, patients must have resolution of all acute toxic effects of any prior surgery' radiotherapy or chemotherapy to National Cancer Institute (NCI) Common Toxicity Criteria version 3.0 grade < 1.
- Patients must have ECOG performance status ≤ 2 (Karnofsky ≥ 60%).
- Patients must have a life expectancy of greater than 3 months.
- Patients must have normal renal and marrow function as defined below:
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- leukocytes ≥ 3,000/μl
- absolute neutrophil count ≥ 1,500/μl
- platelets ≥ 100,000/μl
- haemoglobin ≥ 7g/dL
- creatinine ≤ 1.5 X institutional upper limit of normal
- Patients with abnormal liver function tests (AST/ALT ≤ 3 x institutional upper limits of normal; ALP ≤ 5x ULN; total bilirubin ≤ 2x ULN) will be eligible for enrollment.
- Patients must have adequate renal functions (serum creatinine within normal laboratory limits).
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents.
- Patients who have rapidly progressive intracranial or spinal metastatic disease (including patients who require corticosteroid for CNS disease).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel or ketoconazole used in study.
- Patients who have prior medications known to be metabolized by or induce/inhibit CYP3A4 within 1 week of each treatment cycle.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because docetaxel is embryotoxic/fetotoxic with the potential for abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with docetaxel, breastfeeding should be discontinued if the mother is treated with docetaxel. These potential risks may also apply to other agents used in this study.
Trial locations and contacts
1 site in 1 country.
About this study
Primary Objective:
- To confirm if ketoconazole inhibition of CYP3A activity affects fractional excretion of docetaxel in the urine.
Secondary Objective:
- To compare the metabolite ratios of the major metabolites of docetaxel in the presence and absence of CYP3A inhibition.
Read the detailed description
Introduction: This is a follow-up protocol to an earlier study entitled "A phase I study of docetaxel with ketoconazole modulation in solid tumors" (PH14/01) which showed 2-fold reduction in docetaxel clearance and a clear correlation with renal function.
Aims: The aim of this study is to confirm that ketoconazole inhibition of CYP3A activity changes the urinary excretion profile of docetaxel.
Methodology: This is a single-centre, crossover study. Ten patients (calculated sample size =5, α=0.05, β=0.8, difference in means=5%, within group standard deviation=3) will be accrued and randomly assigned to receive docetaxel at either 75mg/m2 q3w x 1 dose or 70mg q3w x 1 dose with ketoconazole 200mg bid x q3d at cycle 1 of chemotherapy. This will be followed by a 20-day washout period before receiving the other regimen of docetaxel at cycle 2. Blood samples of 5mls each will be drawn at times 0, 0.5h, 1h, 1.5h, 3h, 4h, 6h and 24h after the onset of docetaxel infusion for pharmacokinetics analysis. A 24-hour urine collection commencing on the same day as docetaxel infusion will be required of the patients. All urine over the next 24 hours must be collected and returned to the study coordinator on Day 2 of each study cycle for docetaxel analysis and creatinine clearance determination. The amount of docetaxel excreted by each patient with and without ketoconazole modulation will be determined by a LCMSMS method and compared.
Clinical Relevance: This is to ensure the safe advocation of a dose-sparing strategy established in an earlier study for the costly agent docetaxel by confirming if changes in excretion profile occurs once its major route of hepatic metabolism is blocked.
- Conditions
- Solid Tumors
- Being tested
- Docetaxel, Ketoconazole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DocetaxelDrug
70mg q3wx 1 dose
KetoconazoleDrug
6 doses of oral ketoconazole 200mg bid starting 2 days before, and with 1 dose to be completed after, docetaxel infusion
| Study group | Role | What they receive |
|---|---|---|
| docetaxel only | Experimental | Not described Receives: Drug: Docetaxel |
| docetaxel with ketoconazole | Experimental | Not described Receives: Drug: Docetaxel; Drug: Ketoconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
To confirm if ketoconazole inhibition of CYP3A activity affects fractional excretion of docetaxel in the urine.
Measured: 9 weeks
Secondary outcomes (1)
To compare the metabolite ratios of the major metabolites of docetaxel in the presence and absence of CYP3A inhibition.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2008 (estimated)
- Study startOct 2006
- Primary completionOct 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Haematology-Oncology, National University Hospital, Singapore
- Investigators
- Boon Cher Goh, MBBS, MRCP, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00697437
- Sponsor's protocol ID
- PK01/01/06
- Status last verified
- Dec 2013
- First submitted
- 11 Jun 2008
- Last updated
- 10 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Goh BC, Lee SC, Wang LZ, Fan L, Guo JY, Lamba J, Schuetz E, Lim R, Lim HL, Ong AB, Lee HS. Explaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies. J Clin Oncol. 2002 Sep 1;20(17):3683-90. doi: 10.1200/JCO.2002.01.025.
PubMed 12202670Tham LS, Goh BC, Wang LZ, Yong WP, Wong CI, Lee SC, Soo R, Sukri N, Lee HS. Ketoconazole inhibition of CYP3A activity made midazolam but not docetaxel pharmacokinetics more predictable. (Abstr) 2006 American Society for Clinical Pharmacology and Therapeutics Annual Meeting (Baltimore, MD).
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Ketoconazole Inhibition of CYP3A on Urinary Excretion of Docetaxel
- ClinicalTrials.gov ID
- NCT00697437
- Acronym / sponsor ID
- PK01/01/06
- Conditions
- Solid Tumors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- Oct 2006
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 13 Jun 2008 (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.
Primary Objective:
- To confirm if ketoconazole inhibition of CYP3A activity affects fractional excretion of docetaxel in the urine.
Secondary Objective:
- To compare the metabolite ratios of the major metabolites of docetaxel in the presence and absence of CYP3A inhibition.
Detailed description
Introduction: This is a follow-up protocol to an earlier study entitled "A phase I study of docetaxel with ketoconazole modulation in solid tumors" (PH14/01) which showed 2-fold reduction in docetaxel clearance and a clear correlation with renal function.
Aims: The aim of this study is to confirm that ketoconazole inhibition of CYP3A activity changes the urinary excretion profile of docetaxel.
Methodology: This is a single-centre, crossover study. Ten patients (calculated sample size =5, α=0.05, β=0.8, difference in means=5%, within group standard deviation=3) will be accrued and randomly assigned to receive docetaxel at either 75mg/m2 q3w x 1 dose or 70mg q3w x 1 dose with ketoconazole 200mg bid x q3d at cycle 1 of chemotherapy. This will be followed by a 20-day washout period before receiving the other regimen of docetaxel at cycle 2. Blood samples of 5mls each will be drawn at times 0, 0.5h, 1h, 1.5h, 3h, 4h, 6h and 24h after the onset of docetaxel infusion for pharmacokinetics analysis. A 24-hour urine collection commencing on the same day as docetaxel infusion will be required of the patients. All urine over the next 24 hours must be collected and returned to the study coordinator on Day 2 of each study cycle for docetaxel analysis and creatinine clearance determination. The amount of docetaxel excreted by each patient with and without ketoconazole modulation will be determined by a LCMSMS method and compared.
Clinical Relevance: This is to ensure the safe advocation of a dose-sparing strategy established in an earlier study for the costly agent docetaxel by confirming if changes in excretion profile occurs once its major route of hepatic metabolism is blocked.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| docetaxel only | Experimental | Drug: Docetaxel |
| docetaxel with ketoconazole | Experimental | Drug: Docetaxel, Drug: Ketoconazole |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which docetaxel is indicated.
- Patients must have measurable or evaluable disease.
- With the exception of alopecia, fatigue, nausea and asthenia, patients must have resolution of all acute toxic effects of any prior surgery' radiotherapy or chemotherapy to National Cancer Institute (NCI) Common Toxicity Criteria version 3.0 grade < 1.
- Patients must have ECOG performance status ≤ 2 (Karnofsky ≥ 60%).
- Patients must have a life expectancy of greater than 3 months.
Key exclusion criteria (7 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents.
- Patients who have rapidly progressive intracranial or spinal metastatic disease (including patients who require corticosteroid for CNS disease).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel or ketoconazole used in study.
- Patients who have prior medications known to be metabolized by or induce/inhibit CYP3A4 within 1 week of each treatment cycle.
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 |
|---|---|---|
| Docetaxel70mg q3wx 1 dose | Drug | docetaxel only, docetaxel with ketoconazole |
| Ketoconazole6 doses of oral ketoconazole 200mg bid starting 2 days before, and with 1 dose to be completed after, docetaxel infusion | Drug | docetaxel with ketoconazole |
Primary outcome
To confirm if ketoconazole inhibition of CYP3A activity affects fractional excretion of docetaxel in the urine.
Time frame: 9 weeks
1 secondary outcome
To compare the metabolite ratios of the major metabolites of docetaxel in the presence and absence of CYP3A inhibition.
Time frame: 12 weeks
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 10 Dec 2013.
- Background: PubMed 12202670Goh BC, Lee SC, Wang LZ, Fan L, Guo JY, Lamba J, Schuetz E, Lim R, Lim HL, Ong AB, Lee HS. Explaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies. J Clin Oncol. 2002 Sep 1;20(17):3683-90. doi: 10.1200/JCO.2002.01.025.
- BackgroundTham LS, Goh BC, Wang LZ, Yong WP, Wong CI, Lee SC, Soo R, Sukri N, Lee HS. Ketoconazole inhibition of CYP3A activity made midazolam but not docetaxel pharmacokinetics more predictable. (Abstr) 2006 American Society for Clinical Pharmacology and Therapeutics Annual Meeting (Baltimore, MD).
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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.
Boon Cher Goh, MBBS, MRCP principal investigator
National University Hospital, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Docetaxel and Ketoconazole in people with Solid Tumors, run by National University Hospital, Singapore at 1 site in Singapore.
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 15 inclusion and 7 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 10 Dec 2013. 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 Singapore. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
To confirm if ketoconazole inhibition of CYP3A activity affects fractional excretion of docetaxel in the urine. (time frame: 9 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00697437, which also lists 2 linked publications.
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 10 Dec 2013.