CancerPhase 1NCT01000376
Evaluating the Pharmacokinetics and Tolerance of Co-administration of Oral Multiple Dose of Ketoconazole and an IV (Bolus) Infusion of Eribulin in Patients With Advanced Solid Tumors
A Phase 1 study testing Eribulin alone and Eribulin plus Ketoconazole in people with Cancer, run by Eisai Limited at 1 site in Netherlands.
Trial summary
The purpose of this study is to investigate whether ketoconazole, taken orally, influences the level of eribulin in the blood when the two drugs are given at the same time. The study will enroll patients with solid tumors whose cancer became worse even after standard treatment, or for whom there is no standard… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- Eribulin alone and Eribulin plus 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
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- Feb 2009to Sep 2009
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 a histologically or cytologically confirmed advanced solid tumor that has progressed following standard therapy or for which no standard therapy exists (including surgery or radiation therapy).
- Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy ≤ Grade 2 and alopecia.
- Patients must be aged ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- Life expectancy of ≥ 3 months.
- Patients must have adequate renal function as evidenced by serum creatinine ≤ 2.0 mg/dL (≤ 176 mol/L) or calculated creatinine clearance ≥ 40 mL/minute (min) per the Cockcroft and Gault formula.
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- Patients must have adequate hepatic function as evidenced by bilirubin ≤ 1.5 times the upper limit of normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 3 times the ULN, (in the case of liver metastases ≤ 5 times ULN or in the case of bone metastases, the liver specific alkaline phosphatase ≤ 3 times ULN).
- Patients must have adequate bone marrow function as evidenced by absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, hemoglobin ≥ 10.0 g/dL or ≥ 6.2 mmol/L (a hemoglobin < 10.0 g/dL or < 6.2 mmol/L is acceptable if it is corrected by growth factor or transfusion), and platelets ≥ 100 x 10^9/L.
- Patients must be willing and able to comply with the study protocol for the duration of the study.
- Patients must give written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.
Who cannot join
- Patients who have received any of the following treatments within the specified period before eribulin treatment starts:
- Chemotherapy, radiation or biological therapy within 2 weeks.
- Hormonal therapy within 1 week.
- Any investigational drug within 4 weeks.
- Patients who are receiving anti-coagulant therapy with warfarin or related compounds, other than for line patency and cannot be changed to heparin-based therapy, are not eligible. If a patient is to continue on mini-dose warfarin, then the prothrombin time (PT) or international normalized ratio (INR) must be closely monitored.
- Patients receiving, at the time the study starts, any medication, dietary supplements or other compounds or substances known to induce or inhibit CYP3A4 activity, with the exception of ketoconazole. A comprehensive list can be found at http://medicine/iupui.edu/flockhart/table.htm.
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- Patients for whom the use of ketoconazole is contraindicated.
- Patients who are receiving drugs that might influence ketoconazole metabolism.
- Women who are pregnant or breast-feeding; women of childbearing potential with either a positive pregnancy test at screening or no pregnancy test; women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the Investigator. Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
- Fertile men who are not willing to use contraception or fertile men with a female partner who is not willing to use contraception.
- Patients whose intestinal absorption is impaired.
- Severe/uncontrolled intercurrent illness/infection.
- Significant cardiovascular impairment (history of congestive heart failure > New York Heart Association (NYHA) Grade II, unstable angina or myocardial infarction within the past 6 months, or serious cardiac arrhythmia.
- Patients with organ allografts requiring immunosuppression (not including blood and blood components transfusions).
- Patients with known positive human immunodeficiency virus (HIV) status.
- Patients with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment with eribulin.
- Patients with meningeal carcinomatosis.
- Patients with a hypersensitivity to halichondrin B and/or halichondrin B-like compounds.
- Patients with pre-existing neuropathy > Grade 2.
- Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
The Netherlands Cancer Institute
Amsterdam, North Holland, 1066 CX
About this study
Official title: An Open-Label, Phase I Study to Evaluate the Pharmacokinetics and Tolerance of Co-administration of Oral Multiple Dose of Ketoconazole and an IV (Bolus) Infusion of Eribulin in Patients With Advanced Solid Tumors
The purpose of this study is to investigate whether ketoconazole, taken orally, influences the level of eribulin in the blood when the two drugs are given at the same time. The study will enroll patients with solid tumors whose cancer became worse even after standard treatment, or for whom there is no standard treatment available. The study will also investigate whether eribulin given together with ketoconazole is safe (has few side-effects) and is effective against cancer.
- Conditions
- Cancer
- Being tested
- Eribulin alone, Eribulin plus Ketoconazole
- Keywords
- Cancer, solid tumors
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eribulin aloneDrug
Group 1 Cycle 1 (28 days): Eribulin IV 1.4 mg/m^2 alone on Day 1, then eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 15 and oral ketoconazole 200 mg alone on Day 16. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days.
Eribulin plus KetoconazoleDrug
Group 2 Cycle 1 (28 days): Eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 1, then oral ketoconazole 200 mg alone on Day 2 and eribulin IV 1.4 mg/m^2 alone on Day 15. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Not described Receives: Drug: Eribulin alone |
| Group 2 | Experimental | Not described Receives: Drug: Eribulin plus Ketoconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean (SD) Maximum Observed Concentration (Cmax) of Eribulin
Measured: 7 days after dosing on Days 1 and 15
Mean (SD) Area Under Concentration Time Curve From Zero to Infinity (AUC 0-oo) of Eribulin
Measured: 7 days after dosing on Days 1 and 15
Secondary outcomes (1)
Safety of Eribulin Administered Alone or Coadministered With Oral Ketoconazole, as Measured by Number of Subjects With Adverse Events.
Measured: monitored throughout
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2009 (estimated)
- Study startFeb 2009
- Primary completionAug 2009
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jantien Wanders, M.D., Study director, Eisai Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01000376
- Sponsor's protocol ID
- E7389-E044-109
- Status last verified
- Sep 2013
- First submitted
- 22 Oct 2009
- Last updated
- 23 Sep 2013
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Phase I Study to Evaluate the Pharmacokinetics and Tolerance of Co-administration of Oral Multiple Dose of Ketoconazole and an IV (Bolus) Infusion of Eribulin in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01000376
- Acronym / sponsor ID
- E7389-E044-109
- Conditions
- Cancer
- Keywords
- Cancer, solid tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Eisai LimitedIndustry (pharma, biotech, devices)
- Study start
- Feb 2009
- Primary completion
- Aug 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 23 Oct 2009 (estimated)
- Results
- Posted 23 Sep 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate whether ketoconazole, taken orally, influences the level of eribulin in the blood when the two drugs are given at the same time. The study will enroll patients with solid tumors whose cancer became worse even after standard treatment, or for whom there is no standard treatment available. The study will also investigate whether eribulin given together with ketoconazole is safe (has few side-effects) and is effective against cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Eribulin alone |
| Group 2 | Experimental | Drug: Eribulin plus Ketoconazole |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must have a histologically or cytologically confirmed advanced solid tumor that has progressed following standard therapy or for which no standard therapy exists (including surgery or radiation therapy).
- Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy ≤ Grade 2 and alopecia.
- Patients must be aged ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- Life expectancy of ≥ 3 months.
Key exclusion criteria (20 listed)
- Patients who have received any of the following treatments within the specified period before eribulin treatment starts:
- Patients who are receiving anti-coagulant therapy with warfarin or related compounds, other than for line patency and cannot be changed to heparin-based therapy, are not eligible. If a patient is to continue on mini-dose warfarin, then the prothrombin time (PT) or international normalized ratio (INR) must be closely monitored.
- Patients receiving, at the time the study starts, any medication, dietary supplements or other compounds or substances known to induce or inhibit CYP3A4 activity, with the exception of ketoconazole. A comprehensive list can be found at http://medicine/iupui.edu/flockhart/table.htm.
- Patients for whom the use of ketoconazole is contraindicated.
- Patients who are receiving drugs that might influence ketoconazole metabolism.
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 |
|---|---|---|
| Eribulin aloneGroup 1 Cycle 1 (28 days): Eribulin IV 1.4 mg/m^2 alone on Day 1, then eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 15 and oral ketoconazole 200 mg alone on Day 16. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days. | Drug | Group 1 |
| Eribulin plus KetoconazoleGroup 2 Cycle 1 (28 days): Eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 1, then oral ketoconazole 200 mg alone on Day 2 and eribulin IV 1.4 mg/m^2 alone on Day 15. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days. | Drug | Group 2 |
Primary outcome
Mean (SD) Maximum Observed Concentration (Cmax) of Eribulin
Time frame: 7 days after dosing on Days 1 and 15
Mean (SD) Area Under Concentration Time Curve From Zero to Infinity (AUC 0-oo) of Eribulin
Time frame: 7 days after dosing on Days 1 and 15
1 secondary outcome
Safety of Eribulin Administered Alone or Coadministered With Oral Ketoconazole, as Measured by Number of Subjects With Adverse Events.
Time frame: monitored throughout
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Jantien Wanders, M.D. study director
Eisai Limited
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 Eribulin alone and Eribulin plus Ketoconazole in people with Cancer, run by Eisai Limited at 1 site in Netherlands.
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 10 inclusion and 20 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 23 Sep 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 Netherlands. 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?
Yes. Results are posted in the registry (first posted 23 Sep 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mean (SD) Maximum Observed Concentration (Cmax) of Eribulin (time frame: 7 days after dosing on Days 1 and 15). The study lists 2 primary outcomes in all. 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 23 Sep 2013.