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

• Sponsor: Synta Pharmaceuticals Corp. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01039519
• Collaborator: (none)
• Enrollment: 27
• Locations: 4
• Arm: 1
• Duration (Months): 23
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Stromal Tumor	Drug: Ganetespib	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. 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

3. 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.

4. 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).

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Medical Center	Los Angeles	California	United States	90095
2	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
3	Oregon Health and Science University-Knight Cancer Institute	Portland	Oregon	United States	97239
4	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111-2497

Sponsors and Collaborators

• Synta Pharmaceuticals Corp.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Synta Pharmaceuticals Corp.
• ClinicalTrials.gov Identifier: NCT01039519
• Other Study ID Numbers: 9090-05
• First Posted: Dec 25, 2009
• Last Update Posted: Mar 10, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Synta Pharmaceuticals Corp.: G.I. Stromal Tumor; GIST
• Additional relevant MeSH terms: Gastrointestinal Stromal Tumors

Study Results

Participant Flow

Pre-assignment Detail	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
NOT COMPLETED	27
Period Title: Treatment
STARTED	27
COMPLETED	0
NOT COMPLETED	27

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 Participants	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.4 (8.35)
Sex: Female, Male (Count of Participants)
Female	12 44.4%
Male	15 55.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	27 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	4 14.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 7.4%
White	21 77.8%
More than one race	0 0%
Unknown or Not Reported	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	74.94 (22.095)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	171.57 (10.295)
Body Surface Area (BSA) (m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m^2]	1.863 (0.2909)
Time from Initial Gastrointestinal Stromal Tumor (GIST) Diagnosis to Consent (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	68.71 (34.699)
Time from Metastatic/Unresectable GIST Diagnosis to Consent (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	46.77 (28.606)
Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
0	14 51.9%
1	13 48.1%
Any Prior Exposure to Heat Shock Protein 90 (HSP90) Inhibitors (participants) [Number]
Yes	5 18.5%
No	21 77.8%
Unknown	1 3.7%
Prior Systemic Treatment for GIST (participants) [Number]
Yes	27 100%
No	0 0%
Number of Prior Systemic Treatment Regimens for GIST (regimens) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [regimens]	5.85 (2.476)
Best Response From Prior Systemic Treatment (participants) [Number]
Complete response	3 11.1%
Partial response	6 22.2%
Stable Disease	17 63%
Progressive disease	1 3.7%
Unknown	0 0%

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.
Measure Participants	27
Number [percentage of participants]	18.5 68.5%

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.
Measure Participants	27
Number [percentage of participants]	0 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.
Measure Participants	27
Median (95% Confidence Interval) [months]	1.8

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.
Measure Participants	27
Median (95% Confidence Interval) [months]	10.3

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.
Measure Participants	12
Number [percentage of participants]	66.7 247%

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.
Measure Participants	27
>=1 AE	27 100%
>=1 AE with severity grade >=3	15 55.6%
>= 1 SAE	10 37%
>=1 AE leading to dose modification	10 37%
>=1 AE leading to dose interruption	1 3.7%
>=1 AE leading to study drug discontinuation	3 11.1%
>=1 AE with an outcome of death	1 3.7%

Adverse Events

Time Frame	Day 1 up to Week 51
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 (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ganetespib 200 mg/m^2
	Affected / at Risk (%)	# Events
Total	10/27 (37%)
Blood and lymphatic system disorders
Anaemia	2/27 (7.4%)
Gastrointestinal disorders
Abdominal pain	2/27 (7.4%)
Colonic fistula	1/27 (3.7%)
Gastrointestinal haemorrhage	1/27 (3.7%)
Intussusception	1/27 (3.7%)
Nausea	1/27 (3.7%)
Oesophageal ulcer	1/27 (3.7%)
Vomiting	1/27 (3.7%)
Hepatobiliary disorders
Hepatic pain	1/27 (3.7%)
Infections and infestations
Infection	1/27 (3.7%)
Investigations
Amylase increased	1/27 (3.7%)
Blood bilirubin increased	1/27 (3.7%)
Lipase increased	1/27 (3.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression	1/27 (3.7%)
Psychiatric disorders
Confusional state	1/27 (3.7%)
Other (Not Including Serious) Adverse Events
	Ganetespib 200 mg/m^2
	Affected / at Risk (%)	# Events
Total	27/27 (100%)
Blood and lymphatic system disorders
Anaemia	9/27 (33.3%)
Lymphopenia	2/27 (7.4%)
Leukopenia	1/27 (3.7%)
Neutropenia	1/27 (3.7%)
Cardiac disorders
Tachycardia	3/27 (11.1%)
Arrhythmia superventribular	1/27 (3.7%)
Ear and labyrinth disorders
Ear discomfort	1/27 (3.7%)
Eye disorders
Eye pain	1/27 (3.7%)
Vision blurred	1/27 (3.7%)
Gastrointestinal disorders
Diarrhoea	22/27 (81.5%)
Nausea	13/27 (48.1%)
Vomiting	10/27 (37%)
Constipation	7/27 (25.9%)
Abdominal distension	6/27 (22.2%)
Abdominal pain	5/27 (18.5%)
Abdominal discomfort	4/27 (14.8%)
Abdominal pain lower	4/27 (14.8%)
Abdominal pain upper	2/27 (7.4%)
Abdominal tenderness	2/27 (7.4%)
Dyspepsia	2/27 (7.4%)
Rectal haemorrhage	2/27 (7.4%)
Retching	2/27 (7.4%)
Anal fissure	1/27 (3.7%)
Ascites	1/27 (3.7%)
Frequent bowel movements	1/27 (3.7%)
Haematochezia	1/27 (3.7%)
Haemorrhoidal haemorrhage	1/27 (3.7%)
Haemorrhoids	1/27 (3.7%)
Proctalgia	1/27 (3.7%)
Small intestinal obstruction	1/27 (3.7%)
Stomatitis	1/27 (3.7%)
General disorders
Fatigue	15/27 (55.6%)
Asthenia	2/27 (7.4%)
Malaise	2/27 (7.4%)
Pyrexia	2/27 (7.4%)
Chest pain	1/27 (3.7%)
Chills	1/27 (3.7%)
Early satiety	1/27 (3.7%)
Feeling jittery	1/27 (3.7%)
Influenza like illness	1/27 (3.7%)
Localised oedema	1/27 (3.7%)
Oedema	1/27 (3.7%)
Infections and infestations
Bronchitis	1/27 (3.7%)
Candidiasis	1/27 (3.7%)
Ear infection	1/27 (3.7%)
Eye infection bacterial	1/27 (3.7%)
Fungal skin infection	1/27 (3.7%)
Gastroenteritis viral	1/27 (3.7%)
Labyrinthitis	1/27 (3.7%)
Pharyngitis streptococcal	1/27 (3.7%)
Sinusitis	1/27 (3.7%)
Upper respiratory tract infection	1/27 (3.7%)
Urinary tract infection	1/27 (3.7%)
Injury, poisoning and procedural complications
Contusion	3/27 (11.1%)
Infusion related reaction	3/27 (11.1%)
Post procedural haemorrhage	2/27 (7.4%)
Compression fracture	1/27 (3.7%)
Post procedural complication	1/27 (3.7%)
Seroma	1/27 (3.7%)
Thermal burn	1/27 (3.7%)
Investigations
Blood alkaline phosphatase increased	7/27 (25.9%)
Weight decreased	5/27 (18.5%)
Amylase increased	4/27 (14.8%)
Aspartate aminotransferase increased	4/27 (14.8%)
Lipase increased	4/27 (14.8%)
Activated partial thromboplastin time prolonged	2/27 (7.4%)
Blood creatine phosphokinase increased	2/27 (7.4%)
Alanine aminotransferase increased	1/27 (3.7%)
Blood albumin decreased	1/27 (3.7%)
Blood creatinine increased	1/27 (3.7%)
Blood lactate dehydrogenase increased	1/27 (3.7%)
Blood magnesium decreased	1/27 (3.7%)
Blood phosphorus decreased	1/27 (3.7%)
Blood potassium decreased	1/27 (3.7%)
Electrocardiogram QT prolonged	1/27 (3.7%)
Hypertriglyceridaemia	1/27 (3.7%)
Hypocalcaemia	1/27 (3.7%)
Hypomagnesaemia	1/27 (3.7%)
Hypophosphataemia	1/27 (3.7%)
Metabolism and nutrition disorders
Decreased appetite	5/27 (18.5%)
Hyperglycaemia	5/27 (18.5%)
Dehydration	3/27 (11.1%)
Hyperuricaemia	2/27 (7.4%)
Hypoglycaemia	2/27 (7.4%)
Hypokalaemia	2/27 (7.4%)
Hypercalcaemia	1/27 (3.7%)
Hypercholesterolaemia	1/27 (3.7%)
Hyperkalaemia	1/27 (3.7%)
Hypertriglyceridaemia	1/27 (3.7%)
Hypocalcaemia	1/27 (3.7%)
Hypomagnesaemia	1/27 (3.7%)
Hypophosphataemia	1/27 (3.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/27 (22.2%)
Back pain	6/27 (22.2%)
Myalgia	5/27 (18.5%)
Pain in extremity	2/27 (7.4%)
Flank pain	1/27 (3.7%)
Musculoskeletal discomfort	1/27 (3.7%)
Musculoskeletal pain	1/27 (3.7%)
Temporomandibular joint syndrome	1/27 (3.7%)
Torticollis	1/27 (3.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	1/27 (3.7%)
Nervous system disorders
Headache	10/27 (37%)
Dizziness	4/27 (14.8%)
Presyncope	3/27 (11.1%)
Dysgeusia	2/27 (7.4%)
Peripheral sensory neuropathy	2/27 (7.4%)
Somnolence	2/27 (7.4%)
Paraesthesia	1/27 (3.7%)
Peripheral motor neuropathy	1/27 (3.7%)
Psychiatric disorders
Insomnia	8/27 (29.6%)
Anxiety	2/27 (7.4%)
Confusional state	2/27 (7.4%)
Nightmare	2/27 (7.4%)
Abnormal dreams	1/27 (3.7%)
Agitation	1/27 (3.7%)
Depressed mood	1/27 (3.7%)
Renal and urinary disorders
Bladder pain	1/27 (3.7%)
Fanconi syndrome acquired	1/27 (3.7%)
Proteinuria	1/27 (3.7%)
Urinary hesitation	1/27 (3.7%)
Reproductive system and breast disorders
Polymenorrhoea	1/27 (3.7%)
Respiratory, thoracic and mediastinal disorders
Cough	4/27 (14.8%)
Dyspnoea	2/27 (7.4%)
Dyspnoea exertional	2/27 (7.4%)
Hiccups	1/27 (3.7%)
Increased upper airway secretion	1/27 (3.7%)
Pleural effusion	1/27 (3.7%)
Productive cough	1/27 (3.7%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	5/27 (18.5%)
Eczema	2/27 (7.4%)
Night sweats	2/27 (7.4%)
Dermatitis acneiform	1/27 (3.7%)
Dermatitis contact	1/27 (3.7%)
Exfoliative rash	1/27 (3.7%)
Hair colour changes	1/27 (3.7%)
Nail disorder	1/27 (3.7%)
Onychoclasis	1/27 (3.7%)
Vascular disorders
Hypertension	4/27 (14.8%)
Deep vein thrombosis	1/27 (3.7%)
Flushing	1/27 (3.7%)
Hot flush	1/27 (3.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.