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

This study is currently recruiting participants.
Verified April 2014 by Bayer
Sponsor:
Collaborator:
Onyx Therapeutics, Inc.
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01585870
First received: April 12, 2012
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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: 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

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 ] [ 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 54
Study Start Date: July 2012
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01585870

Contacts
Contact: Bayer Clinical Trials Contact clinical-trials-contact@bayerhealthcare.com

Locations
France
Recruiting
Toulouse, France, 31052
Germany
Recruiting
Freiburg, Baden-Württemberg, Germany, 79106
Recruiting
Heidelberg, Baden-Württemberg, Germany, 69120
Not yet recruiting
Berlin, Germany, 10117
Sponsors and Collaborators
Bayer
Onyx Therapeutics, Inc.
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01585870     History of Changes
Other Study ID Numbers: 15977, 2011-005849-12
Study First Received: April 12, 2012
Last Updated: April 14, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Bayer:
Safety
Tolerability
Pharmacokinetics
Clinical benefit
Sorafenib
Eribulin
advanced metastatic solid tumors

Additional relevant MeSH terms:
Neoplasms
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014