A Study to Determine the Metabolism and Elimination of Carbon-14 Labeled Eribulin Acetate (14C-Eribulin) in Patients With Advanced Solid Tumors

Phase 1

Completed

• Conditions: Advanced Solid Tumors
• Interventions: Drug: eribulin

• Registration Number: NCT00908908
• Lead Sponsor: Eisai Inc.

Brief Summary

The purpose of this study is to determine the metabolism and elimination of carbon-14 labeled eribulin acetate (14C-eribulin) in patients with advanced solid tumors.

Detailed Description

The study will be conducted in two phases, the initial Study phase to administer the radio-labeled 14C-eribulin and collection of PK samples, and the Extension Phase when the patients will continue to receive non-radio-labeled eribulin. In the initial Study phase, patients will receive a single 2 mg flat dose of 14C-eribulin (approximately 80 to 90 microCuries) administered on Cycle 1 Day 1 as an intravenous (IV) bolus injection or infusion over 2-5 minutes. Following this initial dose, patients will remain in the research unit until Day 8 to complete sample collections of urine, blood and feces for PK analysis and determination of 14C-eribulin concentrations between Days 1 and 8.

On Day 8 patients will be re-assessed and discharged, and return on day 15 for physical exam, adverse event evaluation, and lab tests. The patients will then enter the Extension Phase of the study and continue to receive on-radio-labeled eribulin at a dose of 1.4 mg/m\^2 on Days 1 and 8 of every 21 day cycle.

Study Timeline

• Study Start: 2009-03
• Study First Submitted: 2009-05-20
• Study First Submitted QC: 2009-05-24
• Study First Posted: 2009-05-27
• Primary Completion: 2011-05
• Study Completion: 2011-05
• Results First Submitted: 2011-12-22
• Results First Submitted QC: 2011-12-22
• Results First Posted: 2012-01-27
• Status Verified: 2012-03
• Last Update Submitted: 2012-03-07
• Last Update Posted: 2012-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

Not provided

Exclusion Criteria

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

   • chemotherapy, radiation, or biological therapy within three weeks
   • hormonal therapy within one week
   • any investigational drug within 4 weeks
   • systemic unconventional or alternative therapies including, but not limited to, herbal remedies within 4 weeks

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

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

4. Have had major surgery within 4 weeks before starting study treatment

5. Patients with pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.

6. 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.

7. Patients with meningeal carcinomatosis.

8. 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.

9. 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. Peri-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.

10. Patients with severe/uncontrolled intercurrent illness/infection.

11. 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).

12. Patients with organ allografts requiring immunosuppression.

13. Patients with known positive HIV status.

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

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

16. Patients who participated in a prior eribulin clinical trial, whether or not they received eribulin (E7389).

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	eribulin	-

Primary Outcome Measures

Name	Time	Method
Excretion Balance of Radio-labeled 14C-eribulin: Total Recovery of Radioactive Dose in Urine and Feces.	312 hours postdose
Pharmacokinetics: AUC (0-t) for Total Radioactivity in Plasma	Between Days 1 and 8 of Cycle 1	Area under the plasma concentration-time curve from time zero to last quantifiable plasma concentration measuring total radioactivity exposure.
Pharmacokinetics AUC (0-t) for Eribulin in Plasma	Between Days 1 and 8 of Cycle 1	Area under the plasma concentration-time curve from time zero to last quantifiable plasma concentration measuring exposure to eribulin.

Trial Locations

Locations (1)

Netherlands Cancer Institute; 🇳🇱 Amsterdam, Netherlands