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

NCT01173523 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 10-048
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

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.

Conditions

Small Cell Lung Cancer

Keywords

Hsp90 Inhibitor; relapsed; refractory

Outcome Measures

Primary Outcomes (1)

• 8-Week Progression-Free Rate

  The 8-week progression free rate is defined as the percentage of participants achieving complete response (CR), partial response (PR) or stable disease (SD) based on RECIST 1.1 criteria by the time of the first disease assessment (8 weeks). Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions; PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD; and SD is neither sufficient decrease to qualify as PR nor sufficient increase to qualify as progressive disease (PD). PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. Response needed confirmation within 4 weeks. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.

  Disease was evaluated radiographically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity. Relevant for this endpoint was the first 8 week disease re-assessment.

Secondary Outcomes (3)

• Overall Response Rate

  Disease was evaluated radiographically at baseline and every 8 weeks on treatment. Treatment duration was a median of 2 cycles (parallel to 2 months given the 4 week cycle length) and range of 1-2 cycles in this study cohort.

• Progression-Free Survival

  Disease was evaluated radiographically at baseline and every 8 weeks on treatment. Treatment duration was a median of 2 cycles (parallel to 2 months given the 4 week cycle length) and range of 1-2 cycles in this study cohort.

• Overall Survival

  Long-term follow-up for survival occurred every 4 weeks. As of this analysis, follow-up among survivors was a median (range) of 11.5 months (0.9-47.9).

Study Arms (2)

Cohort A: STA-9090

EXPERIMENTAL

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.

Drug: STA-9090

Cohort B: STA-9090

EXPERIMENTAL

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.

Drug: STA-9090

Interventions

STA-9090 DRUG

Also known as: Ganetespib

Cohort A: STA-9090; Cohort B: STA-9090

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of small cell lung cancer and confirmed progressive disease by radiographic study
• \</= 3 prior chemotherapy regimens
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• David M. Jackman, MD: lead
• Massachusetts General Hospital: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Synta Pharmaceuticals Corp.: collaborator

Study Sites (3)

Massacusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Recurrence

Interventions

STA 9090

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: David M. Jackman, MD
• Organization: Dana-Farber Cancer Institute

617.632.3468

Study Officials

• David Jackman, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 29, 2010
• First Posted: August 2, 2010
• Study Start: July 28, 2010
• Primary Completion: June 7, 2013
• Study Completion: November 4, 2016
• Last Updated: April 16, 2019
• Results First Posted: April 11, 2017

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)