Phase II Study of Cediranib (AZD2171) in Patients With Alveolar Soft Part Sarcoma
Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor accounting for less than
1% of soft tissue sarcomas. There is no effective systemic treatment for patients with
metastatic ASPS. Little is known with regards to relevant molecular markers as potential
therapeutic targets. Cediranib (AZD2171), a VEGF/KIT tyrosine kinase inhibitor, has recently
demonstrated antitumor activity in early phase clinical trials, which included 7 adult and 3
pediatric patients with ASPS.
(Bullet) To determine the response rate (PR + CR) of AZD2171 in adult patients with ASPS.
(Bullet) To compare gene expression profiles between pre-treatment and post-treatment biopsy
(Bullet) To determine if pediatric patients with ASPS will experience at least a minimal
response rate when treated with AZD2171
Patients must have histologically or cytologically confirmed metastatic alveolar soft part
(Bullet) < 16 years old BSA must be greater than or equal to 1.04 m2 and subject must be
able to swallow tablets.
(Bullet) Adequate organ function.
Adult patients will be treated with AZD2171 at 30 mg by mouth once a day for 28 days (28-day
cycles). Pediatric patients (< 16 years old) will be treated with 12 mg/m2/day once a day
for 28 day (28-day cycles).
Blood pressure will be monitored weekly for the first 2 cycles then every 2 weeks for the
remainder of the study (unless patients have experienced elevated blood pressure requiring
CT scans will be performed at baseline and every 2 cycles for restaging during the first 18
months; after 18 months, restaging CT scans will be performed every 3 months.
The study will be conducted using an optimal two-stage design in both pediatric and adult
patients. The portion in adults will rule out an unacceptably low 5% clinical response rate
(PR+CR) in favor of a modestly high response rate of 25%. In pediatric patients, the study
will rule out an unacceptably low 5% overall clinical response rate (CR + PR) in favor of a
higher response rate of 35%.
Optional biopsies will be performed in adult patients only at baseline and after 3-5 days of
treatment (D3-D5) to evaluate early drug effect. A third optional biopsy after completion of
4 weeks of therapy (between C1D28 and C2D7) may be collected with the intention of providing
further information about disease response to treatment. Depending on results of initial
gene expression profiles, the timing of the biopsies may be adjusted, but without change in
total number of biopsies per patient.
In a retrospective pilot study, CT scans from 20 consecutive off-study patients will be
rereviewed. RECIST imaging measurements will be compared to volumetric density (Total Volume
of Viable Tumor, TVVT) CT measurements. The objective is to establish whether volumetric
density/percent necrosis algorithms such as TVVT more accurately assess extent of disease
and response to therapy than standard RECIST criteria.
The total accrual ceiling is 73 participants (60 adult and 13 pediatric patients).
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the response rate (PR + CR) of AZD2171 in patients with ASPS.
Shivaani Kummar, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|