Clinical trial NCT01173523
Conditions: Small Cell Lung Cancer
Keywords: Hsp90 Inhibitor relapsed refractory
Sponsor: David M. Jackman, MD
Start date: 2010-07-28; Completion date: 2016-11-04
Enrollment: 25 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief 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.

Detailed description:
OBJECTIVES:

Primary Objective

* To determine the progression-free rate at 8 weeks in participants with relapsed or refractory small cell lung cancer who have received \<3 prior regimens of systemic chemotherapy

Secondary Objectives

* To determine the response rate using radiologic assessment according to standard RECIST 1.1 criteria
* To determine median progression free survival and overall survival
* To characterize the toxicity profile of STA-9090 in this patient population

Exploratory Objectives

* To analyze levels of circulating tumor cells (CTCs) from blood samples obtained serially throughout the study and assess the utility of measuring these cell subsets as a marker of disease burden as well as response to therapy
* To analyze the participant population by identification of gene expression profiles (measured in RNA from available tumor biopsies) associated with the efficacy and resistance to STA-9090

Arms: arm 1: Once weekly IV dosing of STA-9090 200mg/m2 was given weeks 1, 2, and 3 of a 4-week cycle. Participants received treatment until evidence of progressive disease or unacceptable toxicity. Participants were stratified at baseline into 2 distinct prognostic groups. Cohort A participants had relapsed \> 60 days following initial chemotherapy completion. arm 2: Once weekly IV dosing of STA-9090 200mg/m2 was given weeks 1, 2, and 3 of a 4-week cycle. Participants received treatment until evidence of progressive disease or unacceptable toxicity. Participants were stratified at baseline into 2 distinct prognostic groups. Cohort B participants had not responded or had relapsed \</= 60 days from the completion of initial chemotherapy.
Interventions: intervention 1: STA-9090
Intervention descriptions: intervention 1: None

Protocol documents: