Bevacizumab and Sorafenib in Treating Patients With Unresectable Stage III or Stage IV Malignant Melanoma
|Recurrent Melanoma Stage III Skin Melanoma Stage IV Skin Melanoma||Biological: Bevacizumab Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Sorafenib Tosylate||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Response [ Time Frame: 4 months ]
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.
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started of the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
- Safety and Tolerability [ Time Frame: 6 months ]Safety and tolerability of treatment, in terms of toxicity profile and incidence and rating of toxicity, according to NCI CTCAE v3.0 criteria.
- Survival [ Time Frame: 6 months ]Determined by time to progression, progression-free suvival, and overall survival.
|Study Start Date:||August 2006|
|Study Completion Date:||February 2009|
|Primary Completion Date:||February 2009 (Final data collection date for primary outcome measure)|
Experimental: Arm I
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.
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
Correlative studiesDrug: Sorafenib Tosylate
I. 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.
I. Evaluate the safety and tolerability of sorafenib tosylate and bevacizumab in these patients.
II. 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.
III. Describe significant pharmacokinetic interactions between bevacizumab and sorafenib tosylate.
IV. 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.
V. Identify predictive biomarkers of response to this regimen in these patients.
VI. 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00387751
|United States, Texas|
|Cancer Therapy and Research Center at The UT Health Science Center at San Antonio|
|San Antonio, Texas, United States, 78229|
|Principal Investigator:||Muralidhar Beeram||Cancer Therapy and Research Center at The UT Health Science Center at San Antonio|