CancerPhase 1NCT00706095
Study Of Eribulin (E7389) In Patients With Advanced Solid Tumors And Normal Or Reduced Hepatic Function As Per Child-Pugh System
A Phase 1 study testing E7389 in people with Cancer, run by Eisai Inc. at 2 sites in Netherlands.
Trial summary
This is an open-label, three-parallel group pharmacokinetic study. Patients with advanced solid tumors will be assigned to one of three groups to receive I.V. doses of eribulin (E7389). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- E7389
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesNetherlands
- Study dates
- Feb 2008to Apr 2010
- 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)
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
- Life expectancy of ≥ 3 months
- Adequate renal function as evidenced by serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance ≥ 40 mL/minute (min) per the Cockcroft and Gault formula.
- Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, hemoglobin ≥ 10.0 g/dL (a hemoglobin <10.0 g/dL is acceptable if it is corrected by growth factor or transfusion), and platelet count ≥ 100 x 10^9/L
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- Patients willing and able to comply with the study protocol for the duration of the study
- Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.
- Additional Inclusion Criteria for the Group of Patients with No Hepatic Impairment:
- All the general inclusion criteria listed above plus: Normal hepatic function as evidenced by bilirubin ≤ 34 μmol/l (≤2.0 mg/dL) and alkaline phosphatase, alanine transaminase (ALT), and aspartate transaminase (AST) ≤3 times the upper limits of normal (ULN) (in the case of liver metastases ≤5 x ULN), or in the case of bone metastases, the liver specific alkaline phosphatase ≤3 times the upper limits of normal (ULN), and in the case of concomitant liver metastases, ≤5 x ULN.
- Additional Inclusion Criteria for the Group of Patients with Hepatic Impairment:
- All the general inclusion criteria listed above plus:
- Mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic dysfunction according to the Child-Pugh scoring system criteria, where patients with laboratory values within normal ranges will not be included in the Child-Pugh A category
- Or, Moderate hepatic dysfunction (Child-Pugh B) according to the Child-Pugh scoring system criteria
Who cannot join
- Patients who have received any of the following treatments within the specified period before E7389 treatment start:
- Chemotherapy, radiation, biological therapy within 3 weeks.
- Hormonal therapy within 1 week.
- Any investigational drug within 4 weeks.
- Patients with any clinically significant laboratory abnormality except for those parameters influenced by hepatic impairment.
- Patients with severe (Child-Pugh C) hepatic dysfunction according to the Child-Pugh scoring system.
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- Patients with encephalopathy ≥ Grade 1.
- Patients receiving any drug known to induce or inhibit CYP3A4 activity. Clinically significant drugs are listed in a comprehensive list that can be found at http://medicine/iupui.edu/flockhart/table.htm.
- Patients, who require therapeutic anti-coagulant therapy other than for line patency with warfarin or related compounds and cannot be changed to heparin-based therapy, are not eligible.
- 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 are not willing to use contraception
- 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 six months, or serious cardiac arrhythmia).
- Patients with organ allografts requiring immunosuppression (not including blood and blood components transfusions).
- Patients with known positive HIV status.
- Patients with brain or subdural metastases are not eligible, unless they are stable and have completed local therapy and have discontinued the use of corticosteroids for this indication for at least four weeks before starting treatment with E7389.
- Patients with meningeal carcinomatosis.
- Patients with a hypersensitivity to halichondrin B and/or halichondrin B-like compounds.
- Patients who participated in a prior E7389 clinical trial.
- Patients with preexisting 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
2 sites in 1 country.
Netherlands2 sites
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Amsterdam, 1066 CX
Utrecht Medical Centre
Utrecht
About this study
Official title: An Open-label, Parallel Group Study to Explore the Pharmacokinetics of Eribulin Mesylate (E7389) in Patients With Advanced Solid Tumors and Normal or Reduced Hepatic Function According to the Child-Pugh System
This is an open-label, three-parallel group pharmacokinetic study. Patients with advanced solid tumors will be assigned to one of three groups to receive I.V. doses of eribulin (E7389). The three groups are: normal hepatic function, mild hepatic impairment (Child-Pugh A) and moderate hepatic impairment (Child-Pugh B) according to the Child-Pugh System for classifying hepatic impairment.
- Conditions
- Cancer
- Being tested
- E7389
- Keywords
- Cancer, advanced 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.
E7389Drug
Also called Eribulin mesylate
E7389 Intravenous injection starting dose on Day 1 is 1.4 mg/m^2 for normal hepatic function.
E7389Drug
Also called Eribulin mesylate
E7389 Intravenous injection starting dose on Day 1 is 1.1 mg/m^2 for mild hepatic impairment (Child-Pugh A)
E7389Drug
Also called Eribulin mesylate
E7389 Intravenous injection starting dose on Day 1 is 0.7 mg/m^2 for moderate hepatic impairment (Child-Pugh B)
| Study group | Role | What they receive |
|---|---|---|
| E7389 1.4 mg/m^2 | Experimental | Not described Receives: Drug: E7389 |
| E7389 1.1 mg/m^2 | Experimental | Not described Receives: Drug: E7389 |
| E7839 0.7 mg/m^2 | Experimental | Not described Receives: Drug: E7389 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean (SD) Pharmacokinetic (PK) Parameter Area Under Concentration Time Curve From Zero to Infinity (AUC0-oo)
Measured: Pre-dose (-0.5h); post-dose at 15 min, 30 min, 60 min, 2 hrs, 4 hrs, 6 hrs, 10 hrs, 24 hrs, 48 hrs, 72hrs, 96 hrs, 120 hrs and 144 hours.
Mean (SD) Pharmacokinetic (PK) Parameter Maximum Observed Plasma Concentration (Cmax)
Measured: Pre-dose (-0.5h); post-dose at 15 min, 30 min, 60 min, 2 hrs, 4 hrs, 6 hrs, 10 hrs, 24 hrs, 48 hrs, 72hrs, 96 hrs, 120 hrs and 144 hours.
Best Overall Response Per Response Evaluation Criteria in Solid Tumors (RECIST)
Defined as the best response from the start of treatment until disease progression or recurrence. Lesions measured by computed tomography (CT) scan and magnetic resonance imaging (MRI). Objective response rate: complete response (CR-disappearance of all lesions)+ partial response (PR-30% decrease in lesion diameter), Progressive Disease (PD-20% increase in lesion diameter), stable disease (SD-neither shrinkage nor increase of lesions).
Measured: throughout the study and up to 30 days after the last dose of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2008 (estimated)
- Study startFeb 2008
- Primary completionSep 2009
- Study completionApr 2010
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.
- More trials run by Eisai Inc.The 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Prof. JHM Schellens, Principal investigator, National Cancer Institute-Antoni van Leuwenhoek Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00706095
- Sponsor's protocol ID
- E7389-E044-108
- Status last verified
- Mar 2012
- First submitted
- 4 Feb 2008
- Last updated
- 27 Mar 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Parallel Group Study to Explore the Pharmacokinetics of Eribulin Mesylate (E7389) in Patients With Advanced Solid Tumors and Normal or Reduced Hepatic Function According to the Child-Pugh System
- ClinicalTrials.gov ID
- NCT00706095
- Acronym / sponsor ID
- E7389-E044-108
- Conditions
- Cancer
- Keywords
- Cancer, advanced solid tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- Feb 2008
- Primary completion
- Sep 2009 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 27 Jun 2008 (estimated)
- Results
- Posted 30 Jan 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, three-parallel group pharmacokinetic study. Patients with advanced solid tumors will be assigned to one of three groups to receive I.V. doses of eribulin (E7389). The three groups are: normal hepatic function, mild hepatic impairment (Child-Pugh A) and moderate hepatic impairment (Child-Pugh B) according to the Child-Pugh System for classifying hepatic impairment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| E7389 1.4 mg/m^2 | Experimental | Drug: E7389 |
| E7389 1.1 mg/m^2 | Experimental | Drug: E7389 |
| E7839 0.7 mg/m^2 | Experimental | Drug: E7389 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 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)
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
- Life expectancy of ≥ 3 months
- Adequate renal function as evidenced by serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance ≥ 40 mL/minute (min) per the Cockcroft and Gault formula.
Key exclusion criteria (21 listed)
- Patients who have received any of the following treatments within the specified period before E7389 treatment start:
- Patients with any clinically significant laboratory abnormality except for those parameters influenced by hepatic impairment.
- Patients with severe (Child-Pugh C) hepatic dysfunction according to the Child-Pugh scoring system.
- Patients with encephalopathy ≥ Grade 1.
- Patients receiving any drug known to induce or inhibit CYP3A4 activity. Clinically significant drugs are listed in a comprehensive list that can be found at http://medicine/iupui.edu/flockhart/table.htm.
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 |
|---|---|---|
| E7389Also: Eribulin mesylateE7389 Intravenous injection starting dose on Day 1 is 1.4 mg/m^2 for normal hepatic function. | Drug | E7389 1.4 mg/m^2 |
| E7389Also: Eribulin mesylateE7389 Intravenous injection starting dose on Day 1 is 1.1 mg/m^2 for mild hepatic impairment (Child-Pugh A) | Drug | E7389 1.1 mg/m^2 |
| E7389Also: Eribulin mesylateE7389 Intravenous injection starting dose on Day 1 is 0.7 mg/m^2 for moderate hepatic impairment (Child-Pugh B) | Drug | E7839 0.7 mg/m^2 |
Primary outcome
Mean (SD) Pharmacokinetic (PK) Parameter Area Under Concentration Time Curve From Zero to Infinity (AUC0-oo)
Time frame: Pre-dose (-0.5h); post-dose at 15 min, 30 min, 60 min, 2 hrs, 4 hrs, 6 hrs, 10 hrs, 24 hrs, 48 hrs, 72hrs, 96 hrs, 120 hrs and 144 hours.
Mean (SD) Pharmacokinetic (PK) Parameter Maximum Observed Plasma Concentration (Cmax)
Time frame: Pre-dose (-0.5h); post-dose at 15 min, 30 min, 60 min, 2 hrs, 4 hrs, 6 hrs, 10 hrs, 24 hrs, 48 hrs, 72hrs, 96 hrs, 120 hrs and 144 hours.
Best Overall Response Per Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: throughout the study and up to 30 days after the last dose of study drug
Defined as the best response from the start of treatment until disease progression or recurrence. Lesions measured by computed tomography (CT) scan and magnetic resonance imaging (MRI). Objective response rate: complete response (CR-disappearance of all lesions)+ partial response (PR-30% decrease in lesion diameter), Progressive Disease (PD-20% increase in lesion diameter), stable disease (SD-neither shrinkage nor increase of lesions).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2012.
- 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.
Prof. JHM Schellens principal investigator
National Cancer Institute-Antoni van Leuwenhoek Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing E7389 in people with Cancer, run by Eisai Inc. at 2 sites 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 14 inclusion and 21 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 27 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 2 sites 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 30 Jan 2012). 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) Pharmacokinetic (PK) Parameter Area Under Concentration Time Curve From Zero to Infinity (AUC0-oo) (time frame: Pre-dose (-0.5h); post-dose at 15 min, 30 min, 60 min, 2 hrs, 4 hrs, 6 hrs, 10 hrs, 24 hrs, 48 hrs, 72hrs, 96 hrs, 120 hrs and 144 hours.). The study lists 3 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 27 Mar 2012.