Study of Hsp90 Inhibitor, STA-9090 for Relapsed or Refractory Small Cell Lung Cancer
Status:
Completed
Trial end date:
2016-11-04
Target enrollment:
Participant gender:
Summary
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.
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 propose to study the single-agent activity of STA-9090 in a Phase II trial of patients
with relapsed or refractory small cell lung cancer.
Phase:
Phase 2
Details
Lead Sponsor:
David M. Jackman, MD
Collaborators:
Beth Israel Deaconess Medical Center Massachusetts General Hospital Synta Pharmaceuticals Corp.