A Study Evaluating STA-9090 in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor (GIST)

Study Overview
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Brief Summary
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The purpose of this study is to determine if STA-9090 is effective in the treatment of patients with metastatic and/or unresectable GIST.

Detailed Description
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Planned: Stage 1: 23 patients. If ≥4 patients had clinical benefit, an additional 32 patients were to be enrolled. Up to 3 additional patients with platelet-derived growth factor receptor, alpha polypeptide (PDGFRA) mutation were to be enrolled, regardless of the total study enrollment. Stage 2: 55 patients. Progressing to this stage was dependent on Stage 1 results. Analyzed: Stage 1: 27 patients were enrolled and analyzed. The study was not expanded to Stage 2 due to insufficient efficacy.

Official Title
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A Non-randomized, Open Label, Multi-center Phase 2 Study Evaluating the Efficacy and Safety of STA-9090 in Patients With Metastatic and/or Unresectable GIST Resistant or Refractory to Prior Systemic Treatments Including Imatinib and Sunitinib

Conditions
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Gastrointestinal Stromal Tumor

Intervention / Treatment
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* Drug: Ganetespib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be at least 18 years of age at the time of study entry Must have histologically confirmed metastatic and/or unresectable GIST Must have measurable disease on computed tomography or magnetic resonance imaging as defined by Response Evaluation Criteria in Solid Tumors (RECIST) Must have documented failure (due to either progression or intolerance)of at least prior imatinib and sunitinib. Previous administration of other known heat shock protein 90 (Hsp90) inhibitors is permitted Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Must have acceptable laboratory values as defined in the protocol Exclusion Criteria: Known central nervous system metastases Major surgery within 4 weeks prior to receiving STA-9090 Use of any investigational agents within 2 weeks or 6 half-lives of the agent, whichever is shorter prior to receiving STA-9090 No treatment with chronic immunosuppressants Must have otherwise adequate health status as defined in the protocol Left ventricular ejection fraction (LVEF) < than or = 50% at baseline Baseline corrected QT interval (QTc) > 470 msec Pregnant or lactating females

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ganetespib 200 mg/m^2<br>Ganetespib (STA-9090) 200 mg/m^2 intravenous infusion once weekly for 3 consecutive weeks followed by one week dose free interval (3 weeks on and 1 week off represent a treatment cycle). Treatment continues until disease progression or unacceptable toxicity. | Drug: Ganetespib<br>* Ganetespib 200 mg/m^2 during an approximately 1-hour infusion once weekly for three consecutive weeks followed by a treatment-free week. Participants who demonstrate acceptable tolerability and objective clinical benefit (defined by at least stable disease or objective response per RECIST) can continue to receive ganetespib until disease progression or appearance of unacceptable toxicity.<br>* Other names: STA-9090;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Showing Clinical Benefit Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 | Clinical benefit is defined as showing a complete response (CR), a partial response (PR) or stable disease (SD) for at least 16 weeks. CR: disappearance of all target lesions and non-target lesions and no new lesions PR: at least a 30% decrease in the sum of the longest diameter of target lesions, no disease progression for non-target lesions, and no new lesions SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, no disease progression for non-target lesions, and no new lesions | Week 16 up to Week 47 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Showing an Objective Response Based on RECIST Version 1.0 | Objective response included participants whose best response with confirmation was a complete response (CR) or partial response (PR) from first dose until progression or end of study. CR: disappearance of all target lesions and non-target lesions and no new lesions PR: at least a 30% decrease in the sum of the longest diameter of target lesions, no disease progression for non-target lesions, and no new lesions | Week 16 up to Week 47 | 
| Kaplan-Meier Estimate of Progression Free Survival (PFS) | PFS was defined as the time from the baseline CT scan to disease progression per RECIST or death for any cause. Progressive disease (PD) was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions or the unequivocal progression of existing nontarget lesions | Day 1 up to Week 47 | 
| Kaplan-Meier Estimate of Overall Survival | Overall survival was defined as the time from first dose to death or the date last known alive. | Day 1 up to week 97 | 
| Percentage of Participants Showing a Tumor Response During Cycle 1 in Selected Participants Measured by Positron Emission Tomography (PET) | PET imaging was completed on selected patients only from one investigative site. Treatment phase PET and biopsy was completed on any day from Cycle 1 Day 2 through Day 10. PET imaging data were analyzed utilizing the European Organization for Research and Treatment of Cancer (EORTC) PET Study Group guidelines [Young H, Eur J Cancer, 1999]. Tumor response was considered a complete response (CR) or a partial response (PR). | Day 2 to Day 10 | 
| Count of Participants With Treatment-Emergent Adverse Events (AEs) | Treatment-emergent AEs were defined as AEs that occurred from the time of first dose through 30 days after the last dose of study medication. The Investigator graded the severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death A Serious AE is defined as any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or constitutes an important medical event. Dose modification includes dose delay and dose reduction. | Day 1 up to Week 51 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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G.I. Stromal Tumor, GIST