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

NCT01585870 | Completed Phase 1

• 2 other identifiers: 159772011-005849-12
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 4

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.

Conditions

Neoplasms

Keywords

Safety; Tolerability; Pharmacokinetics; Clinical benefit; Sorafenib; Eribulin; advanced metastatic solid tumors

Outcome Measures

Primary Outcomes (4)

• Number of participants with Adverse Events as a Measure of Safety and Tolerability

  Up to 30 months

• AUC (area under the plasma concentration vs time curve) of BAY43-9006

  Up to 9 weeks

• Cmax (maximum drug concentration in plasma after single dose administration) of BAY43-9006

  Up to 9 weeks

• QT time, assessed by QTcF / QTcB (QT interval corrected for heart rate according to Fridericia / Bazett)

  Up to 9 weeks

Secondary Outcomes (1)

• Clinical benefit and response measured by RESIST (1.1) criteria

  Approximately 3-18 weeks depending on tumor response

Study Arms (1)

Sorafenib + Eribulin

EXPERIMENTAL

Drug: Sorafenib (Nexavar, BAY43-9006); Drug: Eribulin

Interventions

Sorafenib (Nexavar, BAY43-9006) DRUG

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.

Sorafenib + Eribulin

Eribulin DRUG

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

Sorafenib + Eribulin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead
• Onyx Therapeutics, Inc.: collaborator

Study Sites (4)

Unknown Facility

Toulouse, 31052, France

Location

Unknown Facility

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Unknown Facility

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Unknown Facility

Berlin, State of Berlin, 10117, Germany

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Sorafenib; eribulin

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2012
• First Posted: April 26, 2012
• Study Start: July 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: October 27, 2015

Record last verified: 2015-10

Locations

DE (3); FR (1)