Small Cell Lung CancerPhase 2NCT01173523
Study of Hsp90 Inhibitor, STA-9090 for Relapsed or Refractory Small Cell Lung Cancer
A Phase 2 study testing STA-9090 in people with Small Cell Lung Cancer, run by David M. Jackman, MD at 3 sites in United States.
Trial 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%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer
- What is being tested?
- STA-9090
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 3 sitesUnited States
- Study dates
- 28 Jul 2010to 4 Nov 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massacusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: 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.
Read more
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.
Read the 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
- Conditions
- Small Cell Lung Cancer
- Being tested
- STA-9090
- Keywords
- Hsp90 Inhibitor, relapsed, refractory
- Medical subject headings
- Small Cell Lung Carcinoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
STA-9090Drug
Also called Ganetespib
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: STA-9090 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
The objective response rate (ORR) was defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Measured: 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
Progression-free survival (PFS) based on the Kaplan-Meier method is defined as the time from study entry to the earliest documentation of disease progression (PD) based on RECIST 1.1 criteria or death. Participants alive without evidence of PD were censored at the date of last adequate disease assessment. Per RECIST 1.1 for target lesions 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. For non-target lesions, progression is appearance of one or more new lesions and/or unequivocal progression on existing non-target lesions.
Measured: 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
Overall survival estimated using Kaplan-Meier (KM) methods is defined as the time from study entry to death due to any cause or date last known alive.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2010 (estimated)
- Study start28 Jul 2010
- Primary completion7 Jun 2013
- Study completion4 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- David M. Jackman, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Synta Pharmaceuticals Corp.
- Responsible party
- Sponsor-investigator, David M. Jackman, MD, Dana-Farber Cancer Institute
- Investigators
- David Jackman, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01173523
- Sponsor's protocol ID
- 10-048
- Status last verified
- Apr 2019
- First submitted
- 29 Jul 2010
- Last updated
- 16 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of the Hsp90 Inhibitor, STA-9090, in Patients With Relapsed or Refractory Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT01173523
- Acronym / sponsor ID
- 10-048
- Conditions
- Small Cell Lung Cancer
- Keywords
- Hsp90 Inhibitor, relapsed, refractory
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- David M. Jackman, MDUniversity, hospital or other
- Collaborators
- Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Synta Pharmaceuticals Corp.
- Study start
- 28 Jul 2010 (actual)
- Primary completion
- 7 Jun 2013 (actual)
- Study completion
- 4 Nov 2016 (actual)
- First posted
- 2 Aug 2010 (estimated)
- Results
- Posted 11 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A: STA-9090 | Experimental | Drug: STA-9090Once 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. |
| Cohort B: STA-9090 | Experimental | Drug: STA-9090Once 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| STA-9090Also: Ganetespib | Drug | Cohort A: STA-9090, Cohort B: STA-9090 |
Primary outcome
8-Week Progression-Free Rate
Time frame: 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.
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.
3 secondary outcomes
Overall Response Rate
Time frame: 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
Time frame: 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
Time frame: 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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Jackman, MD principal investigator
Dana-Farber Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing STA-9090 in people with Small Cell Lung Cancer, run by David M. Jackman, MD at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
8-Week Progression-Free Rate (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2019.