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

• ClinicalTrials.gov Identifier: NCT01039519
• Recruitment Status: Completed
• First Posted: December 25, 2009
• Results First Posted: March 10, 2016
• Last Update Posted: March 10, 2016
• Sponsor: Synta Pharmaceuticals Corp.
• Information provided by (Responsible Party): Synta Pharmaceuticals Corp.

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Gastrointestinal Stromal Tumor
• Intervention: Drug: Ganetespib
• Enrollment: 27

Participant Flow

Recruitment Details
Pre-assignment Details	Thirty-one patients were screened; 4 of the 31 were screen failures.

Arm/Group Title	Ganetespib 200 mg/m^2
Arm/Group Description	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.
Period Title: Treatment
Started	27
Completed	0 [1]
Not Completed	27
Reason Not Completed
Progressive disease	20
Treatment failure	2
Adverse Event	3
Physician Decision	2
[1] Reason not completed represents reason for terminating treatment.
Period Title: Survival Follow-up
Started	27
Completed	0
Not Completed	27
Reason Not Completed
Death	23
Sponsor decision	4

Baseline Characteristics

Arm/Group Title		Ganetespib 200 mg/m^2
Arm/Group Description		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.
Overall Number of Baseline Participants		27
Baseline Analysis Population Description		Full analysis set, which includes participants given at least one dose of study medication.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	27 participants
		54.4 (8.35)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
	Female	12 44.4%
	Male	15 55.6%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	27 100.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
	American Indian or Alaska Native	0 0.0%
	Asian	4 14.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	2 7.4%
	White	21 77.8%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	27 participants
		74.94 (22.095)
Height; Mean (Standard Deviation); Unit of measure: Cm
	Number Analyzed	27 participants
		171.57 (10.295)
Body Surface Area (BSA); Mean (Standard Deviation); Unit of measure: M^2
	Number Analyzed	27 participants
		1.863 (0.2909)
Time from Initial Gastrointestinal Stromal Tumor (GIST) Diagnosis to Consent [1]; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	27 participants
		68.71 (34.699)
		[1] Measure Description: N = 25 participants
Time from Metastatic/Unresectable GIST Diagnosis to Consent [1]; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	27 participants
		46.77 (28.606)
		[1] Measure Description: N = 20 participants GIST = gastrointestinal stromal tumor
Eastern Cooperative Oncology Group (ECOG) Performance Status [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	27 participants
0		14
1		13
		[1] Measure Description: The ECOG scale is as follows: Grade 0: Fully active, able to carry on all pre-disease activities without restriction;; Grade 1: Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature;; Grade 2: Ambulatory and capable of all self-care but unable to work. Up and about more than 50% of waking hours;; Grade 3: Capable of only limited self-care, confined to bed or chair > 50% of waking hours;; Grade 4: Completely disabled. Cannot carry on any self-care. Confined to bed or Chair.
Any Prior Exposure to Heat Shock Protein 90 (HSP90) Inhibitors; Measure Type: Number; Unit of measure: Participants	Number Analyzed	27 participants
Yes		5
No		21
Unknown		1
Prior Systemic Treatment for GIST; Measure Type: Number; Unit of measure: Participants	Number Analyzed	27 participants
Yes		27
No		0
Number of Prior Systemic Treatment Regimens for GIST; Mean (Standard Deviation); Unit of measure: Regimens
	Number Analyzed	27 participants
		5.85 (2.476)
Best Response From Prior Systemic Treatment [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	27 participants
Complete response		3
Partial response		6
Stable Disease		17
Progressive disease		1
Unknown		0
		[1] Measure Description: Target Lesion Response Criteria, RECIST (version 1.0); Complete response - disappearance of all target lesions; Partial response - at least a 30% decrease in the sum of the longest diameter of target lesions; Stable disease - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease; Progressive disease - 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

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Showing Clinical Benefit Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set which included participants receiving at least one dose of study medication.

Arm/Group Title	Ganetespib 200 mg/m^2
Arm/Group Description:	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.
Overall Number of Participants Analyzed	27
Measure Type: Number; Unit of Measure: percentage of participants
	18.5

2. Secondary Outcome

Title	Percentage of Participants Showing an Objective Response Based on RECIST Version 1.0
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Ganetespib 200 mg/m^2
Arm/Group Description:	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.
Overall Number of Participants Analyzed	27
Measure Type: Number; Unit of Measure: percentage of participants
	0

3. Secondary Outcome

Title	Kaplan-Meier Estimate of Progression Free Survival (PFS)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Ganetespib 200 mg/m^2
Arm/Group Description:	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.
Overall Number of Participants Analyzed	27
Median (95% Confidence Interval); Unit of Measure: months
	1.8; (1.6 to 3.5)

4. Secondary Outcome

Title	Kaplan-Meier Estimate of Overall Survival
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Ganetespib 200 mg/m^2
Arm/Group Description:	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.
Overall Number of Participants Analyzed	27
Median (95% Confidence Interval); Unit of Measure: months
	10.3; (5.8 to 13.6)

5. Secondary Outcome

Title	Percentage of Participants Showing a Tumor Response During Cycle 1 in Selected Participants Measured by Positron Emission Tomography (PET)
Description	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

Outcome Measure Data

Analysis Population Description

Participants from one investigative site who provided consent for the PET/CT imaging.

Arm/Group Title	Ganetespib 200 mg/m^2
Arm/Group Description:	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.
Overall Number of Participants Analyzed	12
Measure Type: Number; Unit of Measure: percentage of participants
	66.7

6. Secondary Outcome

Title	Count of Participants With Treatment-Emergent Adverse Events (AEs)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Ganetespib 200 mg/m^2
Arm/Group Description:	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.
Overall Number of Participants Analyzed	27
Measure Type: Number; Unit of Measure: participants
>=1 AE	27
>=1 AE with severity grade >=3	15
>= 1 SAE	10
>=1 AE leading to dose modification	10
>=1 AE leading to dose interruption	1
>=1 AE leading to study drug discontinuation	3
>=1 AE with an outcome of death	1

Adverse Events

Time Frame	Day 1 up to Week 51
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Ganetespib 200 mg/m^2
Arm/Group Description	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.
All-Cause Mortality
	Ganetespib 200 mg/m^2
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Ganetespib 200 mg/m^2
	Affected / at Risk (%)
Total	10/27 (37.04%)
Blood and lymphatic system disorders
Anaemia † 1	2/27 (7.41%)
Gastrointestinal disorders
Abdominal pain † 1	2/27 (7.41%)
Colonic fistula † 1	1/27 (3.70%)
Gastrointestinal haemorrhage † 1	1/27 (3.70%)
Intussusception † 1	1/27 (3.70%)
Nausea † 1	1/27 (3.70%)
Oesophageal ulcer † 1	1/27 (3.70%)
Vomiting † 1	1/27 (3.70%)
Hepatobiliary disorders
Hepatic pain † 1	1/27 (3.70%)
Infections and infestations
Infection † 1	1/27 (3.70%)
Investigations
Amylase increased † 1	1/27 (3.70%)
Blood bilirubin increased † 1	1/27 (3.70%)
Lipase increased † 1	1/27 (3.70%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression † 1	1/27 (3.70%)
Psychiatric disorders
Confusional state † 1	1/27 (3.70%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (15.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Ganetespib 200 mg/m^2
	Affected / at Risk (%)
Total	27/27 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	9/27 (33.33%)
Lymphopenia † 1	2/27 (7.41%)
Leukopenia † 1	1/27 (3.70%)
Neutropenia † 1	1/27 (3.70%)
Cardiac disorders
Tachycardia † 1	3/27 (11.11%)
Arrhythmia superventribular † 1	1/27 (3.70%)
Ear and labyrinth disorders
Ear discomfort † 1	1/27 (3.70%)
Eye disorders
Eye pain † 1	1/27 (3.70%)
Vision blurred † 1	1/27 (3.70%)
Gastrointestinal disorders
Diarrhoea † 1	22/27 (81.48%)
Nausea † 1	13/27 (48.15%)
Vomiting † 1	10/27 (37.04%)
Constipation † 1	7/27 (25.93%)
Abdominal distension † 1	6/27 (22.22%)
Abdominal pain † 1	5/27 (18.52%)
Abdominal discomfort † 1	4/27 (14.81%)
Abdominal pain lower † 1	4/27 (14.81%)
Abdominal pain upper † 1	2/27 (7.41%)
Abdominal tenderness † 1	2/27 (7.41%)
Dyspepsia † 1	2/27 (7.41%)
Rectal haemorrhage † 1	2/27 (7.41%)
Retching † 1	2/27 (7.41%)
Anal fissure † 1	1/27 (3.70%)
Ascites † 1	1/27 (3.70%)
Frequent bowel movements † 1	1/27 (3.70%)
Haematochezia † 1	1/27 (3.70%)
Haemorrhoidal haemorrhage † 1	1/27 (3.70%)
Haemorrhoids † 1	1/27 (3.70%)
Proctalgia † 1	1/27 (3.70%)
Small intestinal obstruction † 1	1/27 (3.70%)
Stomatitis † 1	1/27 (3.70%)
General disorders
Fatigue † 1	15/27 (55.56%)
Asthenia † 1	2/27 (7.41%)
Malaise † 1	2/27 (7.41%)
Pyrexia † 1	2/27 (7.41%)
Chest pain † 1	1/27 (3.70%)
Chills † 1	1/27 (3.70%)
Early satiety † 1	1/27 (3.70%)
Feeling jittery † 1	1/27 (3.70%)
Influenza like illness † 1	1/27 (3.70%)
Localised oedema † 1	1/27 (3.70%)
Oedema † 1	1/27 (3.70%)
Infections and infestations
Bronchitis † 1	1/27 (3.70%)
Candidiasis † 1	1/27 (3.70%)
Ear infection † 1	1/27 (3.70%)
Eye infection bacterial † 1	1/27 (3.70%)
Fungal skin infection † 1	1/27 (3.70%)
Gastroenteritis viral † 1	1/27 (3.70%)
Labyrinthitis † 1	1/27 (3.70%)
Pharyngitis streptococcal † 1	1/27 (3.70%)
Sinusitis † 1	1/27 (3.70%)
Upper respiratory tract infection † 1	1/27 (3.70%)
Urinary tract infection † 1	1/27 (3.70%)
Injury, poisoning and procedural complications
Contusion † 1	3/27 (11.11%)
Infusion related reaction † 1	3/27 (11.11%)
Post procedural haemorrhage † 1	2/27 (7.41%)
Compression fracture † 1	1/27 (3.70%)
Post procedural complication † 1	1/27 (3.70%)
Seroma † 1	1/27 (3.70%)
Thermal burn † 1	1/27 (3.70%)
Investigations
Blood alkaline phosphatase increased † 1	7/27 (25.93%)
Weight decreased † 1	5/27 (18.52%)
Amylase increased † 1	4/27 (14.81%)
Aspartate aminotransferase increased † 1	4/27 (14.81%)
Lipase increased † 1	4/27 (14.81%)
Activated partial thromboplastin time prolonged † 1	2/27 (7.41%)
Blood creatine phosphokinase increased † 1	2/27 (7.41%)
Alanine aminotransferase increased † 1	1/27 (3.70%)
Blood albumin decreased † 1	1/27 (3.70%)
Blood creatinine increased † 1	1/27 (3.70%)
Blood lactate dehydrogenase increased † 1	1/27 (3.70%)
Blood magnesium decreased † 1	1/27 (3.70%)
Blood phosphorus decreased † 1	1/27 (3.70%)
Blood potassium decreased † 1	1/27 (3.70%)
Electrocardiogram QT prolonged † 1	1/27 (3.70%)
Hypertriglyceridaemia † 1	1/27 (3.70%)
Hypocalcaemia † 1	1/27 (3.70%)
Hypomagnesaemia † 1	1/27 (3.70%)
Hypophosphataemia † 1	1/27 (3.70%)
Metabolism and nutrition disorders
Decreased appetite † 1	5/27 (18.52%)
Hyperglycaemia † 1	5/27 (18.52%)
Dehydration † 1	3/27 (11.11%)
Hyperuricaemia † 1	2/27 (7.41%)
Hypoglycaemia † 1	2/27 (7.41%)
Hypokalaemia † 1	2/27 (7.41%)
Hypercalcaemia † 1	1/27 (3.70%)
Hypercholesterolaemia † 1	1/27 (3.70%)
Hyperkalaemia † 1	1/27 (3.70%)
Hypertriglyceridaemia † 1	1/27 (3.70%)
Hypocalcaemia † 1	1/27 (3.70%)
Hypomagnesaemia † 1	1/27 (3.70%)
Hypophosphataemia † 1	1/27 (3.70%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	6/27 (22.22%)
Back pain † 1	6/27 (22.22%)
Myalgia † 1	5/27 (18.52%)
Pain in extremity † 1	2/27 (7.41%)
Flank pain † 1	1/27 (3.70%)
Musculoskeletal discomfort † 1	1/27 (3.70%)
Musculoskeletal pain † 1	1/27 (3.70%)
Temporomandibular joint syndrome † 1	1/27 (3.70%)
Torticollis † 1	1/27 (3.70%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain † 1	1/27 (3.70%)
Nervous system disorders
Headache † 1	10/27 (37.04%)
Dizziness † 1	4/27 (14.81%)
Presyncope † 1	3/27 (11.11%)
Dysgeusia † 1	2/27 (7.41%)
Peripheral sensory neuropathy † 1	2/27 (7.41%)
Somnolence † 1	2/27 (7.41%)
Paraesthesia † 1	1/27 (3.70%)
Peripheral motor neuropathy † 1	1/27 (3.70%)
Psychiatric disorders
Insomnia † 1	8/27 (29.63%)
Anxiety † 1	2/27 (7.41%)
Confusional state † 1	2/27 (7.41%)
Nightmare † 1	2/27 (7.41%)
Abnormal dreams † 1	1/27 (3.70%)
Agitation † 1	1/27 (3.70%)
Depressed mood † 1	1/27 (3.70%)
Renal and urinary disorders
Bladder pain † 1	1/27 (3.70%)
Fanconi syndrome acquired † 1	1/27 (3.70%)
Proteinuria † 1	1/27 (3.70%)
Urinary hesitation † 1	1/27 (3.70%)
Reproductive system and breast disorders
Polymenorrhoea † 1	1/27 (3.70%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	4/27 (14.81%)
Dyspnoea † 1	2/27 (7.41%)
Dyspnoea exertional † 1	2/27 (7.41%)
Hiccups † 1	1/27 (3.70%)
Increased upper airway secretion † 1	1/27 (3.70%)
Pleural effusion † 1	1/27 (3.70%)
Productive cough † 1	1/27 (3.70%)
Skin and subcutaneous tissue disorders
Hyperhidrosis † 1	5/27 (18.52%)
Eczema † 1	2/27 (7.41%)
Night sweats † 1	2/27 (7.41%)
Dermatitis acneiform † 1	1/27 (3.70%)
Dermatitis contact † 1	1/27 (3.70%)
Exfoliative rash † 1	1/27 (3.70%)
Hair colour changes † 1	1/27 (3.70%)
Nail disorder † 1	1/27 (3.70%)
Onychoclasis † 1	1/27 (3.70%)
Vascular disorders
Hypertension † 1	4/27 (14.81%)
Deep vein thrombosis † 1	1/27 (3.70%)
Flushing † 1	1/27 (3.70%)
Hot flush † 1	1/27 (3.70%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (15.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Sponsor has the right, 60 days before submission for publication, to review disclosures and require deletion of its confidential information, excluding the study results. Public disclosure shall be delayed for up to 60 additional days in order for the Sponsor to file a patent application, if needed. Single center publications will be postponed until after disclosure of pooled data (all sites), or, for a period of 18 months from study completion/termination at all participating sites.

Results Point of Contact

• Name/Title: VP Clinical Research
• Organization: Synta Pharmaceuticals
• Phone: 781-541-7156
• EMail: aoneill@syntapharma.com

• Responsible Party: Synta Pharmaceuticals Corp.
• ClinicalTrials.gov Identifier: NCT01039519
• Other Study ID Numbers: 9090-05
• First Submitted: December 23, 2009
• First Posted: December 25, 2009
• Results First Submitted: February 11, 2016
• Results First Posted: March 10, 2016
• Last Update Posted: March 10, 2016