Lung Cancer Clinical Trial

Study of Hsp90 Inhibitor, STA-9090 for Relapsed or Refractory Small Cell Lung Cancer

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.

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Full 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

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Eligibility Criteria

Inclusion Criteria:

Histologically confirmed diagnosis of small cell lung cancer and confirmed progressive disease by radiographic study
Subjects with brain metastases will be allowed if they have been treated with surgery and/or radiation therapy > 21 days prior, are asymptomatic, and are stable for at least 1 week off steroids
Must have measurable disease
>/= 18 years of age
Life expectancy of greater than 12 weeks
EGOG performance status 0 or 1
Lab values must be within limits outlined in the protocol
Not pregnant or breastfeeding
Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Chemotherapy or radiotherapy within 3 weeks or within 5 half-lives of previous therapy
History of severe allergic or hypersensitivity reactions to taxanes.
Subjects who have not recovered from adverse events or toxicities due to agents administered more than 4 weeks earlier to a grade 1 or less
Not receiving any other study agents
History of or current coronary artery disease, myocardial infarction, angina pectoris, angioplasty or coronary bypass surgery.
Baseline QTc > 470 msec or previous history of QT prolongation while taking other medications.
Ventricular ejection fraction of < 55%.
History or current uncontrolled dysrhythmias, or requirement for antiarrhythmic medications, or Grade 2 or greater left bundle branch block.
ECG with clinically significant ventricular arrhythmias or ischemia
Major surgery within 4 weeks of starting treatment
Poor venous access necessitating use of indwelling catheter for IV therapy
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance
History of another malignancy unless disease-free for 3 years and deemed to be at low risk for recurrence

Study is for people with:

Lung Cancer

Phase:

Phase 2

Estimated Enrollment:

25

Study ID:

NCT01173523

Recruitment Status:

Completed

Sponsor:

David M. Jackman, MD

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There are 2 Locations for this study

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Massacusetts General Hospital
Boston Massachusetts, 02114, United States
Beth Israel Deaconess Medical Center
Boston Massachusetts, 02115, United States
Dana Farber Cancer Institute
Boston Massachusetts, 02115, United States

How clear is this clinincal trial information?

Study is for people with:

Lung Cancer

Phase:

Phase 2

Estimated Enrollment:

25

Study ID:

NCT01173523

Recruitment Status:

Completed

Sponsor:


David M. Jackman, MD

How clear is this clinincal trial information?

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