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Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of Sorafenib and Eribulin in Combination

This study has been completed.
Onyx Therapeutics, Inc.
Information provided by (Responsible Party):
Bayer Identifier:
First received: April 12, 2012
Last updated: October 26, 2015
Last verified: October 2015

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.

Condition Intervention Phase
Neoplasms Drug: Sorafenib (Nexavar, BAY43-9006) Drug: Eribulin Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (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

Resource links provided by NLM:

Further study details as provided by Bayer:

Primary Outcome Measures:
  • Number of participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to 30 months ]
  • AUC (area under the plasma concentration vs time curve) of BAY43-9006 [ Time Frame: Up to 9 weeks ]
  • Cmax (maximum drug concentration in plasma after single dose administration) of BAY43-9006 [ Time Frame: Up to 9 weeks ]
  • QT time, assessed by QTcF / QTcB (QT interval corrected for heart rate according to Fridericia / Bazett) [ Time Frame: Up to 9 weeks ]

Secondary Outcome Measures:
  • Clinical benefit and response measured by RESIST (1.1) criteria [ Time Frame: Approximately 3-18 weeks depending on tumor response ]

Enrollment: 40
Study Start Date: July 2012
Study Completion Date: September 2015
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: Eribulin
Eribulin: 1.4 mg/m2 as an intravenous infusion on Days 1 and 8 of each 21-day cycle.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01585870

Toulouse, France, 31052
Freiburg, Baden-Württemberg, Germany, 79106
Heidelberg, Baden-Württemberg, Germany, 69120
Berlin, Germany, 10117
Sponsors and Collaborators
Onyx Therapeutics, Inc.
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer Identifier: NCT01585870     History of Changes
Other Study ID Numbers: 15977
2011-005849-12 ( EudraCT Number )
Study First Received: April 12, 2012
Last Updated: October 26, 2015

Keywords provided by Bayer:
Clinical benefit
advanced metastatic solid tumors

Additional relevant MeSH terms:
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs processed this record on September 19, 2017