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

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ClinicalTrials.gov Identifier: NCT01585870
Recruitment Status : Completed
First Posted : April 26, 2012
Last Update Posted : October 27, 2015
Onyx Therapeutics, Inc.
Information provided by (Responsible Party):

Brief 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.

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
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
Study Start Date : July 2012
Primary Completion Date : September 2015
Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Number of participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to 30 months ]
  2. AUC (area under the plasma concentration vs time curve) of BAY43-9006 [ Time Frame: Up to 9 weeks ]
  3. Cmax (maximum drug concentration in plasma after single dose administration) of BAY43-9006 [ Time Frame: Up to 9 weeks ]
  4. 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 :
  1. Clinical benefit and response measured by RESIST (1.1) criteria [ Time Frame: Approximately 3-18 weeks depending on tumor response ]

Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01585870     History of Changes
Other Study ID Numbers: 15977
2011-005849-12 ( EudraCT Number )
First Posted: April 26, 2012    Key Record Dates
Last Update Posted: October 27, 2015
Last Verified: October 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