Gastrointestinal Stromal Tumor
Conditions
Keywords
G.I. Stromal Tumor, GIST
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.
Interventions
DRUGGanetespib
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.
Sponsors
Synta Pharmaceuticals Corp.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Pre-assignment details
Thirty-one patients were screened; 4 of the 31 were screen failures.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Survival Follow-up | Death | 23 |
| Survival Follow-up | Sponsor decision | 4 |
| Treatment | Adverse Event | 3 |
| Treatment | Physician Decision | 2 |
| Treatment | Progressive disease | 20 |
| Treatment | Treatment failure | 2 |
Baseline characteristics
| Characteristic | Ganetespib 200 mg/m^2 |
|---|---|
| Age, Continuous | 54.4 years STANDARD_DEVIATION 8.35 |
| Any Prior Exposure to Heat Shock Protein 90 (HSP90) Inhibitors No | 21 participants |
| Any Prior Exposure to Heat Shock Protein 90 (HSP90) Inhibitors Unknown | 1 participants |
| Any Prior Exposure to Heat Shock Protein 90 (HSP90) Inhibitors Yes | 5 participants |
| Best Response From Prior Systemic Treatment Complete response | 3 participants |
| Best Response From Prior Systemic Treatment Partial response | 6 participants |
| Best Response From Prior Systemic Treatment Progressive disease | 1 participants |
| Best Response From Prior Systemic Treatment Stable Disease | 17 participants |
| Best Response From Prior Systemic Treatment Unknown | 0 participants |
| Body Surface Area (BSA) | 1.863 m^2 STANDARD_DEVIATION 0.2909 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 14 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 13 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 171.57 cm STANDARD_DEVIATION 10.295 |
| Number of Prior Systemic Treatment Regimens for GIST | 5.85 regimens STANDARD_DEVIATION 2.476 |
| Prior Systemic Treatment for GIST No | 0 participants |
| Prior Systemic Treatment for GIST Yes | 27 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 15 Participants |
| Time from Initial Gastrointestinal Stromal Tumor (GIST) Diagnosis to Consent | 68.71 months STANDARD_DEVIATION 34.699 |
| Time from Metastatic/Unresectable GIST Diagnosis to Consent | 46.77 months STANDARD_DEVIATION 28.606 |
| Weight | 74.94 kg STANDARD_DEVIATION 22.095 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 27 / 27 |
| serious Total, serious adverse events | 10 / 27 |
Outcome results
Primary
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
Time frame: Week 16 up to Week 47
Population: Full analysis set which included participants receiving at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ganetespib 200 mg/m^2 | Percentage of Participants Showing Clinical Benefit Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 | 18.5 percentage of participants |
Secondary
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.
Time frame: Day 1 up to Week 51
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ganetespib 200 mg/m^2 | Count of Participants With Treatment-Emergent Adverse Events (AEs) | >=1 AE | 27 participants |
| Ganetespib 200 mg/m^2 | Count of Participants With Treatment-Emergent Adverse Events (AEs) | >=1 AE with severity grade >=3 | 15 participants |
| Ganetespib 200 mg/m^2 | Count of Participants With Treatment-Emergent Adverse Events (AEs) | >= 1 SAE | 10 participants |
| Ganetespib 200 mg/m^2 | Count of Participants With Treatment-Emergent Adverse Events (AEs) | >=1 AE leading to dose modification | 10 participants |
| Ganetespib 200 mg/m^2 | Count of Participants With Treatment-Emergent Adverse Events (AEs) | >=1 AE leading to dose interruption | 1 participants |
| Ganetespib 200 mg/m^2 | Count of Participants With Treatment-Emergent Adverse Events (AEs) | >=1 AE leading to study drug discontinuation | 3 participants |
| Ganetespib 200 mg/m^2 | Count of Participants With Treatment-Emergent Adverse Events (AEs) | >=1 AE with an outcome of death | 1 participants |
Secondary
Kaplan-Meier Estimate of Overall Survival
Overall survival was defined as the time from first dose to death or the date last known alive.
Time frame: Day 1 up to week 97
Population: Full analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ganetespib 200 mg/m^2 | Kaplan-Meier Estimate of Overall Survival | 10.3 months |
Secondary
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
Time frame: Day 1 up to Week 47
Population: Full analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ganetespib 200 mg/m^2 | Kaplan-Meier Estimate of Progression Free Survival (PFS) | 1.8 months |
Secondary
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
Time frame: Week 16 up to Week 47
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ganetespib 200 mg/m^2 | Percentage of Participants Showing an Objective Response Based on RECIST Version 1.0 | 0 percentage of participants |
Secondary
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).
Time frame: Day 2 to Day 10
Population: Participants from one investigative site who provided consent for the PET/CT imaging.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ganetespib 200 mg/m^2 | Percentage of Participants Showing a Tumor Response During Cycle 1 in Selected Participants Measured by Positron Emission Tomography (PET) | 66.7 percentage of participants |