Advanced Solid Tumors
Conditions
Keywords
Advanced Solid Tumors, Failure of Multiple Prior Chemotherapy Regimens
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.
Interventions
DRUGeribulin
Cycle 1 day 1: radio-labeled dose of 2 mg radioactive eribulin, followed by 1.4 mg/m\^2 of non-radio-labeled eribulin thereafter on days 1 and 8 every 21 days.
Sponsors
Eisai Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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). Patients with measurable tumors according to RECIST are desirable but not essential. 2. Patients must be aged 18 years or older. 3. Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0,1, or 2. 4. Patients must have adequate renal function as evidenced by serum creatinine ≤135 µM/L (≤1.5 mg/dL) or creatinine clearance \>= 40 mL/minute (min). 5. Patients must have adequate bone marrow function as evidenced by absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L and platelet count \>= 100 x 10\^9/L. 6. 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 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. 7. Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or below, except for stable sensory neuropathy ≤ Grade 2 and alopecia. 8. Patients must be willing and able to comply with the study protocol for the duration of the study. 9. 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.
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Netherlands
Participant flow
Recruitment details
This study was recruited at 1 center in The Netherlands during the period of Mar 2009 to Jun 2009.
Participants by arm
| Arm | Count |
|---|---|
| Eribulin Cycle 1 Day 1: radio-labeled dose of 2 mg radioactive eribulin, followed by 1.4 mg/m\^2 of non-radio-labeled eribulin thereafter on Days 1 and 8 every 21 days. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Eribulin |
|---|---|
| Age Continuous | 57.5 years STANDARD_DEVIATION 13.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Excretion Balance of Radio-labeled 14C-eribulin: Total Recovery of Radioactive Dose in Urine and Feces.
Time frame: 312 hours postdose
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 14C-eribulin/Eribulin | Excretion Balance of Radio-labeled 14C-eribulin: Total Recovery of Radioactive Dose in Urine and Feces. | 90.4 percent recovery | Standard Deviation 11.73 |
Primary
Pharmacokinetics AUC (0-t) for Eribulin in Plasma
Area under the plasma concentration-time curve from time zero to last quantifiable plasma concentration measuring exposure to eribulin.
Time frame: Between Days 1 and 8 of Cycle 1
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 14C-eribulin/Eribulin | Pharmacokinetics AUC (0-t) for Eribulin in Plasma | 301 ng eq*hr/mL/mg | Standard Deviation 164.9 |
Primary
Pharmacokinetics: AUC (0-t) for Total Radioactivity in Plasma
Area under the plasma concentration-time curve from time zero to last quantifiable plasma concentration measuring total radioactivity exposure.
Time frame: Between Days 1 and 8 of Cycle 1
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 14C-eribulin/Eribulin | Pharmacokinetics: AUC (0-t) for Total Radioactivity in Plasma | 269 ng eq*hr/mL/mg | Standard Deviation 153.4 |