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

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

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

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Stromal Tumor
• Intervention / Treatment: Drug: Ganetespib

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University-Knight Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ganetespib 200 mg/m^2; 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; 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.; Other Names: STA-9090

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Synta Pharmaceuticals Corp.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: December 23, 2009
• First Submitted That Met QC Criteria: December 24, 2009
• First Posted (Estimate): December 25, 2009

Study Record Updates

• Last Update Posted (Estimate): March 10, 2016
• Last Update Submitted That Met QC Criteria: February 11, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: GIST; G.I. Stromal Tumor
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors
• Other Study ID Numbers: 9090-05