A Phase II, Pharmacokinetic (PK), Pharmacodynamic (PD) and Biological Correlative Study of the Efficacy and Safety of Dual Antiangiogenic Inhibition Using Bevacizumab and Sorafenib in Patients With Advanced Malignant Melanoma
- Determine the clinical biologic activity of sorafenib tosylate and bevacizumab, defined
as the sum of complete response, partial response, and prolonged stable disease for ≥
16 weeks, in patients with unresectable stage III or stage IV malignant melanoma
previously treated with at least 2 regimens of immunotherapy, cytokines, biologic
therapy, or vaccine therapy or in previously untreated patients who are not appropriate
candidates to receive aldesleukin-based treatment.
- Evaluate the safety and tolerability of sorafenib tosylate and bevacizumab in these
- Evaluate the biologic activity of this regimen, in terms of time to progression,
progression-free survival at 6 months, and overall survival, in these patients.
- Describe significant pharmacokinetic interactions between bevacizumab and sorafenib
- Characterize the pharmacodynamic relationships between the plasma concentration of
sorafenib tosylate and bevacizumab and the effects of treatment on normal organ
function and tumor tissue in these patients.
- Identify predictive biomarkers of response to this regimen in these patients.
- Correlate changes in biological measurements with patient outcomes.
OUTLINE: This is an open-label, multicenter study.
Patients receive oral sorafenib tosylate on days 1-5, 8-12, 15-19, and 22-26 and bevacizumab
IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days in the absence of
unacceptable toxicity or disease progression.
Blood samples and tumor biopsies are obtained periodically for pharmacokinetic and
pharmacodynamic studies. Samples are examined by liquid chromatography, mass spectrometry,
immunohistochemistry, gene expression analysis, DNA mutation analysis, and genomic analysis
for biological markers.
After completion of study treatment, patients are followed for 4 weeks.
PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.
Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Clinical biologic activity of treatment, defined as the sum of complete response, partial response, and prolonged stable disease for ≥ 16 weeks, upon treatment with the combination of sorafenib and bevacizumab, in patients with advanced metastatic melanoma previously treated with immunotherapy or in previously untreated patients who are not appropriate candidates to receive IL-2-based treatment.
John Sarantopoulos, MD
University of Texas Health Science Center San Antonio
United States: Food and Drug Administration
|Brooke Army Medical Center||Fort Sam Houston, Texas 78234-6200|
|Cancer Therapy and Research Center||San Antonio, Texas 78229|