Pilot Study of Liposomal Doxorubicin Combined With Bevacizumab Followed by Bevacizumab Monotherapy in Adults With Advanced Kaposi's Sarcoma
- Standard treatment for advanced Kaposi's sarcoma (KS) is a liposomal anthracycline,
plus antiretroviral therapy (HAART) in patients with HIV.
- KS is not curable and relapses are common. Prolonged use of liposomal anthracyclines
with cumulative dosing exceeding 550 mg/m(2) is frequently required.
- KS is notable for pathogenic autocrine and paracrine VEGF signaling. The monoclonal
antibody, bevacizumab is a rational agent for the treatment of KS.
- Preliminary results from our phase II study of bevacizumab monotherapy, 03-C0110,
suggest that bevacizumab has promising activity in the treatment of KS.
- The combination of anti-angiogenic therapy with cytotoxic chemotherapy has been a
successful strategy in KS as well as other solid tumors.
- This pilot study will evaluate the activity and safety of liposomal doxorubicin
combined with bevacizumab followed by bevacizumab maintenance in patients with advanced
KS. A goal of this combination strategy is to develop a tolerable and highly active
regimen that would limit the need for prolonged anthracycline use.
- The primary objective is to estimate the overall response rate (ORR) of six cycles of
liposomal doxorubicin combined with bevacizumab in patients with advanced KS.
- Secondary objectives include evaluation of the safety of the regimen, as well as
estimation of the complete response rate after 6 cycles, the median number of cycles
need to obtain a partial response, and 12-month progression-free survival.
- Age greater than or equal to 18
- Biopsy proven KS
- Indication for chemotherapy
- Any HIV status
- Normal MUGA
- Able to tolerate aspirin 81 mg
- SBP < 150, DBP < 90
- Urine protein < 1+ or 500mg/24hrs
- Surgery within 4 weeks
- Thrombo-embolic disease
- Chemotherapy within 3 weeks
- Hemoptysis or gastrointestinal bleeding, unless caused by KS
- Pregnancy or breast feeding
- This is an open label, single center pilot with 2 cohorts. Cohort 1: HIV negative, HIV
infected with stable KS despite 1 year of HAART with HIV viremic control, or HIV
infected with progressive KS despite 4 months of HAART with HIV viremic control.
Cohort 2: All other patients with advanced AIDS-associated KS.
- Subjects will receive bevacizumab 15 mg/kg and liposomal doxorubicin 20 mg/m(2) every 3
weeks until complete response (CR) or a maximum of 6 cycles. Those with stable disease
or better will continue on bevacizumab 15 mg/kg monotherapy every 3 weeks for 11
cycles. HIV infected subjects will receive HAART.
- ORR will be calculated with 80% CI for each cohort separately. If estimates in the two
cohorts are similar (p> 0.30 by a Fisher's exact test), they may be combined to form a
somewhat more precise estimate of ORR after 6 cycles of treatment.
- A total of 10 evaluable patients will be accrued in each cohort.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary objective is to estaimate the overall response rate (ORR) of six cycles of liposomal doxorubicin combined with bevacizumab in patients with advanced KS.
Robert Yarchoan, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|