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

Phase 2

Completed

Conditions: Gastrointestinal Stromal Tumor

Interventions: Drug: Ganetespib

Registration Number: NCT01039519

Lead Sponsor: Synta Pharmaceuticals Corp.

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 27

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ganetespib 200 mg/m^2	Ganetespib	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Showing Clinical Benefit Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0	Week 16 up to Week 47	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

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Showing an Objective Response Based on RECIST Version 1.0	Week 16 up to Week 47	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
Kaplan-Meier Estimate of Progression Free Survival (PFS)	Day 1 up to Week 47	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
Kaplan-Meier Estimate of Overall Survival	Day 1 up to week 97	Overall survival was defined as the time from first dose to death or the date last known alive.
Percentage of Participants Showing a Tumor Response During Cycle 1 in Selected Participants Measured by Positron Emission Tomography (PET)	Day 2 to Day 10	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).
Count of Participants With Treatment-Emergent Adverse Events (AEs)	Day 1 up to Week 51	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.

Trial Locations

Locations (4): Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
Oregon Health and Science University-Knight Cancer Institute
🇺🇸
Portland, Oregon, United States
UCLA Medical Center
🇺🇸
Los Angeles, California, United States
Dana Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States