QT Interval Prolongation Study of Eribulin Mesylate (E7389) in Patients With Advanced Solid Tumors

NCT01106248 | Completed Phase 1 Results

• 1 other identifier: E7389-E044-110
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to assess whether eribulin mesylate (E7389) has an impact on the electrocardiogram (ECG) with focus on cardiac repolarization, as measured by QT/QTc interval as well as through a pharmacokinetic-pharmacodynamic (PK/PD) analysis.

Conditions

Advanced Solid Tumor

Keywords

tumor

Outcome Measures

Primary Outcomes (1)

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

  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.

  48 hours postdose after Day 1 and after Day 8

Secondary Outcomes (4)

• Pharmacokinetic Profile of Eribulin Mesylate: Observed Maximal Plasma Concentration (Cmax)

  Days 1 and 8

• To Assess Best Overall Response Using RECIST Criteria in Patients With Measurable Disease.

  21 day cycle

• To Further Explore the Safety and Tolerability of Eribulin Mesylate When Administered on Days 1 and 8 of a 21-day Cycle in Patients With Solid Tumors.

  21 day cycle

• Pharmacokinetic Profile of Eribulin Mesylate: Time to Maximum Observed Plasma Concentration (Tmax).

  Days 1 and 8

Study Arms (1)

Eribulin Mesylate

OTHER

Drug: Eribulin Mesylate

Interventions

Eribulin Mesylate DRUG

1.4 mg/m\^2 intravenous (IV) bolus given over 2-5 minutes on Days 1 and 8 every 21 days.

Eribulin Mesylate

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy \</= Grade 2 and alopecia.
• Age \>/= 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
• Patients must have a sinus rhythm and QRS \< 120msec.
• Adequate renal function as evidenced by serum creatinine \</= 2.0 mg/dL or calculated creatinine clearance \>/= 40 mL/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.
• 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) \</= 3 x ULN (in the case of liver metastases \</= 5 x ULN), 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.
• 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.

You may not qualify if:

• 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
• Have had radiation therapy encompassing \> 30% of bone marrow.
• Have received prior treatment with mitomycin C or nitrosourea.
• Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
• 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 weeks.
• Patients with meningeal carcinomatosis.
• 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).
• Patients with marked baseline prolongation of QT/QTc interval (QTc interval \> 500 msec).
• 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).
• Patients with uncontrolled metabolic disorders (e.g hypokalemia, hypercalcemia and hypomagnesemia) at entry to the study.
• Patients treated with antiarrythmic drugs or other medications that prolong the QT/QTc, that cannot be discontinued prior to entry into the study phase.
• Patients with implantable pacemaker or automatic implantable cardioverter defibrillator (AICD).

Sponsors & Collaborators

• Eisai Limited: lead

Study Sites (2)

Medicale

Dunkirk, *CS, 44229, France

Location

Service d'Oncologie

Dunkirk, *CS, 44229, France

Location

MeSH Terms

Conditions

Neoplasms

Interventions

eribulin

Results Point of Contact

• Title: Dr. Peter Tarassoff
• Organization: Eisai

888-422-4743

Study Officials

• Jantien Wanders, MD

  Eisai Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2010
• First Posted: April 19, 2010
• Study Start: March 1, 2009
• Primary Completion: September 1, 2010
• Last Updated: April 13, 2012
• Results First Posted: April 13, 2012

Record last verified: 2012-03

Locations

FR (2)