check_circleStudy Completed

Neoplasms

Bayer Identifier:

15977

ClinicalTrials.gov Identifier:

NCT01585870

EudraCT Number:

2011-005849-12

EU CT Number:

Not Available
Safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of sorafenib and eribulin in combination

Trial 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.

Key Participants Requirements

Sex

Both

Age

18 - N/A
  • - 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
  • - 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

Trial summary

Enrollment Goal
40
Trial Dates
July 2012 - September 2015
Phase
Phase 1
Could I Receive a placebo
No
Products
Nexavar (Sorafenib, BAY43-9006)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Heidelberg, 69120, Germany
Completed
Berlin, 10117, Germany
Completed
Freiburg, 79106, Germany
Completed
TOULOUSE, 31052, France

Primary Outcome

  • Number of participants with Adverse Events as a Measure of Safety and Tolerability
    date_rangeTime Frame:
    Up to 30 months
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    Safety Issue:
    Yes
  • AUC (area under the plasma concentration vs time curve) of BAY43-9006
    date_rangeTime Frame:
    Up to 9 weeks
    enhanced_encryption
    Safety Issue:
    No
  • Cmax (maximum drug concentration in plasma after single dose administration) of BAY43-9006
    date_rangeTime Frame:
    Up to 9 weeks
    enhanced_encryption
    Safety Issue:
    No
  • QT time, assessed by QTcF / QTcB (QT interval corrected for heart rate according to Fridericia / Bazett)
    date_rangeTime Frame:
    Up to 9 weeks
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    Safety Issue:
    Yes

Secondary Outcome

  • Clinical benefit and response measured by RESIST (1.1) criteria
    date_rangeTime Frame:
    Approximately 3-18 weeks depending on tumor response
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    Safety Issue:
    No

Trial design

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
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
N/A
Blinding
Open Label
Assignment
Single Group Assignment
Trial Arms
1

Additional Information

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