A Phase II Study of the Hsp90 Inhibitor, STA-9090, in Patients With Relapsed or Refractory Small Cell Lung Cancer
Small cell lung cancer (SCLC) is a chemotherapy and radiotherapy sensitive tumor, but with
very high rates of relapse and metastasis, resulting in a very poor outcome. Among
limited-stage patients, the relapse rate is at least 80% and among extensive-stage patients,
the relapse rate is 95-98%. The impetus to develop more effective therapies against novel
targets in SCLC is therefore high. Hsp-90 inhibitors are a new class of drugs with important
anti-malignant potential in a variety of tumor types because of the reliance of multiple
oncoproteins on Hsp90 function.
Although small cell neuroendocrine tumors generally carry many mutated oncoproteins, without
clearly defined clients for Hsp90 mediating inhibitor effects in these cells, a recent study
demonstrated that Hsp90 inhibition causes massive apoptosis by activating the intrinsic
apoptotic pathway in a number of SCLC cell lines. SCLC is a particularly attractive target
for apoptosis inducing drugs because of high growth rates and evidence of molecular
alterations affecting apoptotic mechanisms. STA-9090 is a novel, small-molecule inhibitor of
Hsp90. Unlike earlier generations of Hsp90 inhibitors, STA-9090 has been shown to be a
potent inducer of apoptosis in a variety of cell lines and has anti-tumor activity in
multiple types of human xenografts. As was seen with other Hsp90 inhibitors, STA-9090 also
induces apoptosis in a number of SCLC cell lines (T. Shimamura and G. Shapiro, personal
communication).
Based on the anti-tumor potential seen pre-clinically with Hsp90 inhibition, the potent
effects of STA-9090 seen pre-clinically as compared with other inhibitors in the same class,
as well as early data suggesting safety and tolerability of this drug in the Phase I
setting, we are evaluating the single-agent activity of STA-9090 in a Phase II trial of
patients with relapsed or refractory small cell lung cancer.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression-free rate at 8 weeks in subjects with relapsed or refractory SCLC who have received = 3 prior regimens of systemic chemotherapy
2 years
No
Leena Gandhi, MD, PhD
Principal Investigator
Dana-Farber Cancer Institute
United States: Food and Drug Administration
10-048
NCT01173523
July 2010
Name | Location |
---|---|
Beth Israel Deaconess Medical Center | Boston, Massachusetts 02215 |
Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
Massacusetts General Hospital | Boston, Massachusetts 02114 |