Single Agent Sorafenib in Advanced Solid Tumors: Phase II Evaluation of Dose Re-Escalation Following a Dose Reduction (IST000375)
- To evaluate the feasibility of re-escalating the dose of sorafenib tosylate in patients
with advanced malignant solid tumors who initially required a dose reduction for
toxicity, and dose escalation in those patients who are able to tolerate the initial
- To evaluate the efficacy of this drug in these patients who are able to tolerate a dose
escalation initially or after a dose reduction compared to those who are unable to
tolerate a dose escalation.
- To evaluate the percentage and demographic characteristics of patients who are able to
tolerate 2 dose escalations without a dose reduction.
OUTLINE: This is a dose-finding study.
- Course 1: Patients receive oral sorafenib tosylate twice daily at dose level 0 on weeks
- Course 2: Patients experiencing no dose-limiting or intolerable toxicities receive oral
sorafenib tosylate at dose level +1 twice daily on weeks 5-8; while patients
experiencing dose-limiting or intolerable toxicities receive oral sorafenib tosylate at
dose level -1 once daily on weeks 5-8.
- Course 3: Depending on whether or not patients are experiencing dose-limiting or
intolerable toxicities, they are escalated to dose level 0 or dose level +2 (patients
in both dose levels receive oral sorafenib tosylate twice daily) in weeks 9-12, or
de-escalated to dose level 0 or dose level -2 (patients in dose level -2 receives oral
sorafenib tosylate once every other day) in weeks 9-12.
- Maintenance therapy: Patients receive oral sorafenib tosylate at the dose level*
attained at the end of course 3. Treatment continues in the absence of unacceptable
NOTE: *Dose level de-escalation for toxicity or dose re-escalation after a toxicity-related
dose reduction allowed to a maximum level of the initial dose level of the maintenance
After completion of study therapy, patients are followed for up to 1 year.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Percentage of patients who are able to maintain a re-escalated dose of sorafenib tosylate for 28 days without dose interruption or de-escalation for toxicity
At least 3 months
Primo N. Lara, MD
University of California, Davis
United States: Food and Drug Administration
|University of California Davis Cancer Center||Sacramento, California 95817|