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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Synta Pharmaceuticals Corp.
ClinicalTrials.gov Identifier:
NCT01039519
First received: December 23, 2009
Last updated: February 11, 2016
Last verified: February 2016
  Purpose
The purpose of this study is to determine if STA-9090 is effective in the treatment of patients with metastatic and/or unresectable GIST.

Condition Intervention Phase
Gastrointestinal Stromal Tumor
Drug: Ganetespib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Synta Pharmaceuticals Corp.:

Primary Outcome Measures:
  • Percentage of Participants Showing Clinical Benefit Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 [ Time Frame: Week 16 up to Week 47 ] [ Designated as safety issue: No ]

    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:
  • Percentage of Participants Showing an Objective Response Based on RECIST Version 1.0 [ Time Frame: Week 16 up to Week 47 ] [ Designated as safety issue: No ]

    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) [ Time Frame: Day 1 up to Week 47 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 1 up to week 97 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 2 to Day 10 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1 up to Week 51 ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 27
Study Start Date: January 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: STA-9090

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01039519

Locations
United States, California
UCLA Medical Center
Los Angeles, California, United States, 90095
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Oregon
Oregon Health and Science University-Knight Cancer Institute
Portland, Oregon, United States, 97239
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
Sponsors and Collaborators
Synta Pharmaceuticals Corp.
  More Information

Responsible Party: Synta Pharmaceuticals Corp.
ClinicalTrials.gov Identifier: NCT01039519     History of Changes
Other Study ID Numbers: 9090-05 
Study First Received: December 23, 2009
Results First Received: February 11, 2016
Last Updated: February 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Synta Pharmaceuticals Corp.:
G.I. Stromal Tumor
GIST

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue

ClinicalTrials.gov processed this record on May 22, 2016