A Dose-Finding Study of E7389 in Combination With Carboplatin in Patients With Solid Tumors
|Cancer||Drug: E7389 + carboplatin AUC 5 Drug: E7389 + carboplatin AUC 6 Drug: E7389+carboplatin AUC 6||Phase 1|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase Ib Open-Label, Two-Arm, Dose-Finding Study of E7389 in Combination With Carboplatin in Patients With Solid Tumors|
- Maximum Tolerated Dose (MTD) of Eribulin Mesylate of E7389 in Combination With Carboplatin in Subjects With Advanced Solid Tumors. [ Time Frame: 21 days (first cycle) ]MTD was established by summarizing the number and percent of subject with dose- limiting toxicities (DLTs) for the first cycle.
- Safety of Eribulin Mesylate in Combination With Carboplatin as Measured by the Number of Subjects With Treatment Emergent Adverse Events. [ Time Frame: Throughout the entire study ]Adverse events were considered treatment emergent if they started on or after the date of administration of the first dose of study drug, or if they were present prior to the administration of the first dose of study drug and increased in severity during the study.
- Percent of Subjects With Best Overall Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. [ Time Frame: From start of eribulin treatment until disease progression or death ]Objective response measured by Response Evaluation Criteria In Solid Tumors (RECIST) criteria and is Complete Response (disappearance of all target lesions) plus Partial Response (at least 30% decrease in sum of longest diameter [LD] of target lesions compared baseline sum of LD).
|Study Start Date:||October 2006|
|Primary Completion Date:||November 2011 (Final data collection date for primary outcome measure)|
Drug: E7389 + carboplatin AUC 5
Patients will receive E7389 before (Schedule A) or after (Schedule B) carboplatin AUC 5 infusion. E7389 will be administered as a 2-5 minute intravenous (IV) bolus infusion at a starting dose of 0.7 mg/m^2 on Days 1 and 8 every 21 days. Carboplatin 5 AUC will be administered as a 30-minute IV infusion on Day 1 every 21 days. Dose escalation will be performed in cohorts of three patients per dose level per schedule.
Drug: E7389 + carboplatin AUC 6
After MTD is reached with carboplatin AUC 5, dose escalation of E7389 in combination with carboplatin at AUC 6 will begin at one dose level below MTD, using the preferred schedule (A or B).
If carboplatin AUC 6 with E7389 is tolerated, the MTD reached will be used to enroll 20 additional patients with Stage IIIB or IV non-small cell lung cancer (NSCLC). If carboplatin AUC 6 is not tolerated, these patients will be enrolled at the MTD determined with the combination of E7389 and carboplatin AUC 5.
Drug: E7389+carboplatin AUC 6
In a population of patients who had generally received multiple prior chemotherapies, the eribulin MTD has been determined to be 1.1 mg/m2 in combination with carboplatin at an AUC of 6. The first-line NSCLC patients in the extension arm may tolerate a higher dose of eribulin, because they have not been exposed to the toxicity of other chemotherapies. To investigate this possibility, the dose of eribulin will be increased to 1.4 mg/m2 for subsequent patients, if the first six of these patients do not experience a DLT during their first cycle of eribulin at 1.1 mg/m2 and carboplatin at AUC 6 combination therapy. If no more than one of the first six patients experience a DLT during the first cycle with the 1.4 mg/m2 dose of eribulin, then the 1.4 mg/m2 dose will be considered the recommended dose for front-line NSCLC therapy and the remaining patients will be treated using this dose.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00268905
|United States, New Jersey|
|New Brunswick, New Jersey, United States|
|United States, New York|
|Bronx, New York, United States|
|Lake Success, New York, United States|
|New York, New York, United States|
|Vijayawada, Andhra Pradesh, India|
|New Delhi, Delhi, India|
|Pune, Maharashtra, India|
|Melur, Tamil Nadu, India|
|Study Director:||Eisai US Medical Services||Eisai Inc.|