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An Open-Label, Multicenter, Single Arm QT Interval Prolongation Study of Eribulin Mesylate (E7389) in Patients With Advanced Solid Tumors

Phase 1
Not Enrolling
Advanced Solid Tumor

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Trial Information

An Open-Label, Multicenter, Single Arm QT Interval Prolongation Study of Eribulin Mesylate (E7389) in Patients With Advanced Solid Tumors

This is an open-label, multicenter, single arm QT Interval prolongation study of eribulin
mesylate (E7389) in patients with advanced solid tumors.

Personal history of unexplained syncope within the last year prior to entry

Inclusion Criteria:

1. Patients with 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).

2. Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or
lower, except for stable sensory neuropathy
3. Age >/= 18 years.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.

5. Patients must have a sinus rhythm and QRS < 120msec.

6. Adequate renal function as evidenced by serum creatinine creatinine clearance >/= 40 mL/min per the Cockcroft and Gault formula.

7. 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.

8. Adequate liver function as evidenced by bilirubin >/= 1.5 times the upper limits of
normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate
aminotransferase (AST) unless there are bone metastases, in which case liver specific alkaline phosphatase
must be separated from the total and used to assess the liver function instead of the
total alkaline phosphatase.

9. Patients willing and able to comply with the study protocol for the duration of the

10. Written informed consent prior to any study-specific screening procedures with the
understanding that the patient may withdraw consent at any time without prejudice.

Exclusion Criteria:

1. Patients who have received any of the following treatments within the specified
period before start of treatment with eribulin mesylate:

- Chemotherapy, radiation or biological therapy within three weeks

- Hormonal therapy within one week

- Any investigational drug within four weeks

2. Have had radiation therapy encompassing > 30% of bone marrow.

3. Have received prior treatment with mitomycin C or nitrosourea.

4. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring
active treatment, including the use of oxygen.

5. 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 in this study. Any signs
(e.g. radiologic) and/or symptoms of brain metastases must be stable for at least 4

6. Patients with meningeal carcinomatosis.

7. Significant cardiovascular impairment (history of congestive heart failure > NYHA
grade II, unstable angina or myocardial infarction within the past six months, or
serious cardiac arrhythmia).

8. Patients with marked baseline prolongation of QT/QTc interval (QTc interval > 500

9. Patients with a history of additional risk factors for Torsades des pointes (e.g.,
heart failure, cardiac ischemia, recent Myocardial Infarction (MI), family history of
Long QT Syndrome).

10. Patients with uncontrolled metabolic disorders (e.g hypokalemia, hypercalcemia and
hypomagnesemia) at entry to the study.

11. Patients treated with antiarrythmic drugs or other medications that prolong the
QT/QTc, that cannot be discontinued prior to entry into the study phase.

12. Patients with implantable pacemaker or automatic implantable cardioverter
defibrillator (AICD).

13. .Bradycardia (defined as
14. Personal history of unexplained syncope within the last year prior to entry into the

15. Patients with other significant disease or disorders that, in the Investigator's
opinion, should exclude the patient from the study.

16. 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.

17. 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.

18. Severe/uncontrolled intercurrent illness/infection.

19. Patients with organ allografts requiring immunosuppression.

20. Patients with known positive HIV status.

21. Patients who have had a prior malignancy, other than carcinoma in situ of the cervix,
or non-melanoma skin cancer, unless the prior malignancy was diagnosed and
definitively treated >/= 5 years previously with no subsequent evidence of

22. Patients with pre-existing neuropathy > Grade 2.

23. Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical

24. Patients who participated in a prior eribulin mesylate clinical trial.

25. Patients with pericardial effusion or pericardial metastases.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Mean Time-matched, Baseline Corrected QTcF at Any Time Point Postdosing.

Outcome Description:

The primary endpoint is mean time-matched, baseline corrected QTcF at any time point postdosing. This was to determine the effect of eribulin on cardiac repolarization as measured by QT/QTc interval.

Outcome Time Frame:

48 hours postdose after Day 1 and after Day 8

Safety Issue:


Principal Investigator

Jantien Wanders, MD

Investigator Role:

Study Director

Investigator Affiliation:

Eisai Inc.


European Union: European Medicines Agency

Study ID:




Start Date:

March 2009

Completion Date:

Related Keywords:

  • Advanced Solid Tumor
  • tumor
  • Neoplasms