Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of Sorafenib and Eribulin in Combination
This Phase 1 study will be conducted in an open-label, non-randomized, dose-escalation design in subjects with advanced, metastatic or refractory solid malignancy who are not candidates for standard therapy. The study drugs are sorafenib and eribulin mesylate.
Up to 24 subjects with solid tumors will participate in the dose escalation part of the study, and once the maximum tolerated dose is defined, up to 30 subjects with advanced, metastatic or refractory solid tumors will participate in the expansion phase of the study.
Eribulin (mesylate) will be administered intravenously at a fixed dose of 1.4 mg/m2 on Days 1 and 8 of 21-day Cycles.
The starting sorafenib dose (Dose Level 1) is 200 mg twice daily. Sorafenib is given orally, continuously on days 11 to 21 of Cycle 1, and from Day 1 to Day 21 of all subsequent cycles. If 200 mg sorafenib twice daily is tolerated with eribulin, the sorafenib dose will be escalated sequentially to 200 mg morning dose and 400 mg evening dose (Dose Level 2) in a new cohort. If Dose Level 2 is tolerated, a second dose escalation to 400 mg twice daily (Dose Level 3) will be studied in a new cohort. If the starting dose of sorafenib is not tolerated with eribulin, the sorafenib dose will be de-escalated to 200 mg once daily in a new cohort. Subjects will need to receive two cycles of eribulin plus sorafenib therapy and safety data for the first and second cycle needs to be available before the start of the next cohort.
|Study Design:||Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1, Multi-center, Non-randomized, Open Label, Dose Escalation Design Study of Sorafenib (BAY43-9006) in Combination With Eribulin in Subjects With Advanced, Metastatic or Refractory Solid Tumors|
- Number of participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to 30 months ] [ Designated as safety issue: Yes ]
- AUC (area under the plasma concentration vs time curve) of BAY43-9006 [ Time Frame: Up to 9 weeks ] [ Designated as safety issue: No ]
- Cmax (maximum drug concentration in plasma after single dose administration) of BAY43-9006 [ Time Frame: Up to 9 weeks ] [ Designated as safety issue: No ]
- QT time, assessed by QTcF / QTcB (QT interval corrected for heart rate according to Fridericia / Bazett) [ Time Frame: Up to 9 weeks ] [ Designated as safety issue: Yes ]
- Clinical benefit and response measured by RESIST (1.1) criteria [ Time Frame: Approximately 3-18 weeks depending on tumor response ] [ Designated as safety issue: No ]
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||April 2015|
|Estimated Primary Completion Date:||April 2015 (Final data collection date for primary outcome measure)|
|Experimental: Sorafenib + Eribulin||
Drug: Sorafenib (Nexavar, BAY43-9006)
Sorafenib (starting dose of 200 mg bid, level 1) administration will begin on Day 11 of Cycle 1, and will be administered twice daily continuously. If the combination is well tolerated, the dose will be escalated in new cohorts to 200 mg AM and 400 mg PM (level 2), then subsequently to 400 mg bid (level 3).
If sorafenib starting dose (level 1) is not well tolerated with eribulin, the sorafenib dose will be de-escalated to 200 mg qd (Dose Level -1) in a new cohort.
Eribulin: 1.4 mg/m2 as an intravenous infusion on Days 1 and 8 of each 21-day cycle.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01585870
|Toulouse, France, 31052|
|Freiburg, Baden-Württemberg, Germany, 79106|
|Heidelberg, Baden-Württemberg, Germany, 69120|
|Berlin, Germany, 10117|
|Study Director:||Bayer Study Director||Bayer|