Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of Sorafenib and Eribulin in Combination
Information source: Bayer
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Neoplasms
Intervention: Sorafenib (Nexavar, BAY43-9006) (Drug); Eribulin (Drug)
Phase: Phase 1
Status: Active, not recruiting
Sponsored by: Bayer Official(s) and/or principal investigator(s): Bayer Study Director, Study Director, Affiliation: Bayer
Summary
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.
Clinical Details
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
Study design: Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Number of participants with Adverse Events as a Measure of Safety and TolerabilityAUC (area under the plasma concentration vs time curve) of BAY43-9006 Cmax (maximum drug concentration in plasma after single dose administration) of BAY43-9006 QT time, assessed by QTcF / QTcB (QT interval corrected for heart rate according to Fridericia / Bazett)
Secondary outcome: Clinical benefit and response measured by RESIST (1.1) criteria
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Subjects with advanced, metastatic or refractory solid malignancy who are not
candidates for standard therapy. For subject with metastatic breast cancer, prior
therapy should have included an anthracycline and a taxane in either the adjuvant or
metastatic setting.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate bone marrow, cardiac, liver, renal and pancreatic function
- Predicted life expectancy of at least 12 weeks
Exclusion Criteria:
- Prolonged corrected QT (QTc), defined as QTcF (QT interval corrected for heart rate
according to Fridericia) interval > 450 msec at screening by central reader
- Cardiac disease: Congestive heart failure > NYHA Class II; subjects must not have
unstable angina (angina symptoms at rest) or new-onset angina (began within the last
3 months) or myocardial infarction within the past 6 months; cardiac ventricular
arrhythmias requiring anti-arrhythmic therapy
- Arterial or venous thrombi, including cerebrovascular accident and myocardial
infarction in the past 6 months
- Pulmonary hemorrhage event ≥ CTCAE (common toxicity criteria for adverse events)
Grade 2 within 4 weeks
- Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks
- Chemotherapy, hormonal therapy, investigational drugs, or radiotherapy within the
last 28 days and/or not recovered (< Grade 1) from prior therapy. Start of study
treatment is allowed within less than 28 days of the prior therapy provided that 5
half-lives of the prior treatment drug(s) have elapsed.
- Use of medication that may prolong QTc
Locations and Contacts
Toulouse 31052, France
Berlin 10117, Germany
Freiburg, Baden-Württemberg 79106, Germany
Heidelberg, Baden-Württemberg 69120, Germany
Additional Information
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Starting date: July 2012
Last updated: July 28, 2015
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