Abraxane and Avastin as Therapy for Patients With Malignant Melanoma, a Phase II Study
It has been suggested that chemotherapy administration may be synergistic with the effects
of an antiangiogenic agent such as Avastin. A "Proof of Principal" of the concept of the
synergistic effects of chemotherapy and antiangiogenic therapy has been shown in the
favorable results reported with temozolomide administered in combination with thalidomide in
melanoma, the favorable results reported for the use of FOLFOX4 in combination with Avastin
in previously treated patients with advanced or metastatic colorectal cancer, and the
approval of the combination of Avastin with 5-fluorouracil-based chemotherapy in the
treatment of patients with metastatic carcinoma of the colon or rectum.
A number of lines of evidence suggest that the combination of Abraxane and Avastin may be
effective as first-line therapy for melanoma:
- Taxanes are active agents in melanoma:
1. In a clinical trial in patients who had failed combination chemotherapy (the
Dartmouth regimen, there was a 24% response rate in patients treated with
paclitaxel (in combination with tamoxifen).
2. Paclitaxel is being used in a Phase III trial with carboplatin and Sorafenib in
patients with metastatic melanoma who have failed no more than one previous
systemic chemotherapeutic treatment.
3. In a phase II trial of docetaxel in patients with metastatic melanoma, objective
responses lasting more than 2 years were observed.
- Abraxane is a taxane that has efficacy superior to that of Taxol for the treatment of
metastatic breast cancer. Abraxane was evaluated as first- and second-line therapy for
patients with metastatic melanoma. Results were encouraging. In this study, Abraxane
will be combined with Avastin in an effort to improve the clinical benefit and prolong
the time to disease progression.
The primary end-point of the study is progression-free survival (PFS) at 4 months.
Secondary end-points include progression-free survival, overall survival (OS), objective
Response Rate (RR) in patients with measurable lesions, time to objective response, duration
of objective response in patients with measurable lesions, and safety and tolerability of
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression-free survival (PFS) at 4 months
April 2007 through December 2009
Lynn E. Spitler, MD
Northern California Melanoma Center
United States: Institutional Review Board
|Northern California Melanoma Center||San Francisco, California 94109|
|The Angeles Clinic and Research Institute||Los Angeles, California 90025|