Study of Pazopanib in the Treatment of Surgically Unresectable or Metastatic Liposarcoma

• Sponsor: Vector Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT01506596
• Collaborator: Novartis (Industry)
• Enrollment: 42
• Locations: 9
• Arm: 1
• Duration (Months): 48
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effectiveness and safety of single agent pazopanib in subjects with unresectable or metastatic liposarcoma.

Condition or Disease	Intervention/Treatment	Phase
Liposarcoma; Surgically Unresectable Liposarcoma; Metastatic Liposarcoma	Drug: pazopanib	Phase 2

Detailed Description

This is a Phase II, multicenter, prospective, open label, single arm study. The primary endpoint of the study is progression-free rate as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.1 at week 12 after start of treatment. The secondary endpoints include overall progression-free survival (PFS), response rate (RR), duration of response, overall survival (OS), and toxicity assessment through the reporting of adverse events.

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Pazopanib in the Treatment of Surgically Unresectable or Metastatic Liposarcoma
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: pazopanib Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity.	Drug: pazopanib; Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity.; Other Names: Votrient

Outcome Measures

Primary Outcome Measures

1. 12-week Progression Free Rate [Assessed after 12 weeks of study treatment]

   Progression will be as defined per Response Evaluation Criteria In Solid Tumors (RECIST) guidelines version 1.1. Subjects who remain under observation and progression free at 12 weeks will be defined as treatment successes. Subjects who progress per RECIST by 12 weeks or who drop out without evidence of progression prior to 12 weeks will be defined as treatment failures.Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as a >=20% increase in the sum of diameters of target lesions, or a measurable increase in a non-target lesion, or the appearance of >=1 new lesion.

Secondary Outcome Measures

1. Progression Free Survival (PFS) [Date of Consent until progression or death, up to 27 months]

   PFS was measured from date of consent until the subject experiences disease progression (assessed approximately every 12 weeks) or death, whichever came first, up to 27 months. Repeat radiologic imaging will be conducted after every 3 cycles of treatment (approximately every 12 weeks) to evaluate disease status per RECIST v1.1. Subjects who discontinue study treatment for reasons other than disease progression will continue to have their disease status reported every 3 months post end of treatment up to 27 months.

2. Best Overall Response [Date of consent until end of study treatment, up to 32 months]

   Best overall response is defined as the best response across all time points. Repeat radiologic imaging was conducted after every 3 cycles of treatment (approximately every 12 weeks). Response was evaluated using RECIST v1.1 guidelines, where complete response (CR) is the disappearance of all target and non-target lesions; partial response (PR) is >=30% decrease in the sum of diameters of target lesions; progressive disease (PD) is >=20% increase in the sum of diameters of target lesions, or a measurable increase in a non-target lesion, or the appearance of >=1 new lesion; stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

3. Duration of Response [Measure of the amount of time that the criteria for response per RECIST are first met until disease progression]

   Response is defined as Complete Response (CR) or Partial Response (PR) per RECIST v1.1. Repeat radiologic imaging will be conducted after every 3 cycles of treatment (approximately every 12 weeks) to evaluate disease status per RECIST v1.1. Confirmation of CR or PR is required by repeat scans that should be performed 4 weeks after the criteria for response are first met.

4. Overall Survival (OS) [Date of Consent until death, up to 32 months]

   OS was measured from date of consent until time of death from any cause, up to 32 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent.

• Age > or = to 18 years.

• Histologically or cytologically confirmed high- or intermediate-grade liposarcoma (allowed subtypes include liposarcoma dedifferentiated, myxoid/round cell, pleomorphic, mixed-type, or not otherwise specified).

• Surgically unresectable or metastatic disease.

• Any number of prior treatment treatment regimens, including treatment naive subjects.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Measurable or evaluable (non-measurable) disease per RECIST guidelines version 1.1. Subjects must have documented disease progression within the past 6 months.

• Adequate organ system function determined within 14 days prior to first dose of study treatment.

• Left ventricular ejection fraction (LVEF) > 50% of the institutional LLN within 28 days prior to the first dose of study treatment.

• Females must be of either non-child bearing potential or have a negative pregnancy test within 7 days prior to the first dose of study treatment.

Exclusion Criteria:

• Well differentiated liposarcoma.

• Prior treatment with tyrosine kinase inhibitors (TKIs) or vascular endothelial growth factor (VEGF) inhibitors.

• Prior malignancy (Note: subjects who have had another malignancy and have been disease-free for 3 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible).

• History or clinical evidence of central nervous system metastases or leptomeningeal carcinomatosis, unless previously treated, asymptomatic, and off steroids and anti-seizure medication for 6 months prior to first dose of study drug

• Clinically significant gastrointestinal (GI) abnormalities that may increase the risk for GI bleeding.

• Clinically significant GI abnormalities that may affect absorption of investigational product.

• Presence of uncontrolled infection.

• Corrected QT interval > 480 msecs using Bazett's formula.

• History of certain cardiovascular conditions within the past 6 months.

• Poorly controlled hypertension [defined as systolic blood pressure of > or = 140 mmHg or diastolic blood pressure > or = 90 mmHg].

• History of cerebrovascular accident including transient ischemic attack, pulmonary embolism, or untreated deep vein thrombosis within the past 6 months.

• Prior major surgery or trauma within 28 days prior to the first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.

• Evidence of active bleeding or bleeding diathesis.

• Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.

• Hemoptysis in excess of 2.5 mL within 8 weeks of first dose of study drug.

• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.

• Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug, whichever is longer, prior to the first dose of study drug and for the duration of study treatment.

• Radiation therapy, minor surgery, tumor embolization, chemotherapy, immunotherapy, biologic therapy, investigational therapy, or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug.

• Administration of any non-oncologic investigational drug within 30 days or five half-lives (whichever is longer) prior to receiving the first dose of study drug.

• Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity, except alopecia.

• Known immediate or delayed hypersensitivity reaction to idiosyncrasy to drugs chemically realted to pazopanib or excipients that contraindicates participation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sarcoma Oncology Center	Santa Monica	California	United States	90403
2	Washington Cancer Institute	Washington	District of Columbia	United States	20010
3	Kootenai Cancer Center	Post Falls	Idaho	United States	83854
4	Oncology Specialists, SC	Niles	Illinois	United States	60714
5	University of Iowa	Iowa City	Iowa	United States	52242
6	University of Minnesota	Minneapolis	Minnesota	United States	55455
7	Pennsylvania Oncology Hematology Associates	Philadelphia	Pennsylvania	United States	19106
8	West Clinic	Memphis	Tennessee	United States	38120
9	MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Vector Oncology
• Novartis

Investigators

• Study Chair: Brian L Samuels, MD, Northwest Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Vector Oncology
• ClinicalTrials.gov Identifier: NCT01506596
• Other Study ID Numbers: ABLSMLS1101
• First Posted: Jan 10, 2012
• Last Update Posted: Feb 15, 2017
• Last Verified: Mar 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Vector Oncology: Liposarcoma
• Additional relevant MeSH terms: Liposarcoma

Study Results

Participant Flow

Arm/Group Title	Pazopanib
Arm/Group Description	Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity. pazopanib: Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	42
COMPLETED	41
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Pazopanib
Arm/Group Description	Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity. pazopanib: Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity.
Overall Participants	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.0 (15.52)
Gender (Count of Participants)
Female	14 34.1%
Male	27 65.9%
Region of Enrollment (participants) [Number]
United States	41 100%

Outcome Measures

1. Primary Outcome

Title	12-week Progression Free Rate
Description	Progression will be as defined per Response Evaluation Criteria In Solid Tumors (RECIST) guidelines version 1.1. Subjects who remain under observation and progression free at 12 weeks will be defined as treatment successes. Subjects who progress per RECIST by 12 weeks or who drop out without evidence of progression prior to 12 weeks will be defined as treatment failures.Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as a >=20% increase in the sum of diameters of target lesions, or a measurable increase in a non-target lesion, or the appearance of >=1 new lesion.
Time Frame	Assessed after 12 weeks of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pazopanib
Arm/Group Description	Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity. pazopanib: Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity.
Measure Participants	41
Number (95% Confidence Interval) [percentage of participants]	68.29 166.6%

2. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS was measured from date of consent until the subject experiences disease progression (assessed approximately every 12 weeks) or death, whichever came first, up to 27 months. Repeat radiologic imaging will be conducted after every 3 cycles of treatment (approximately every 12 weeks) to evaluate disease status per RECIST v1.1. Subjects who discontinue study treatment for reasons other than disease progression will continue to have their disease status reported every 3 months post end of treatment up to 27 months.
Time Frame	Date of Consent until progression or death, up to 27 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pazopanib
Arm/Group Description	Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity. pazopanib: Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity.
Measure Participants	41
Median (95% Confidence Interval) [months]	4.44

3. Secondary Outcome

Title	Best Overall Response
Description	Best overall response is defined as the best response across all time points. Repeat radiologic imaging was conducted after every 3 cycles of treatment (approximately every 12 weeks). Response was evaluated using RECIST v1.1 guidelines, where complete response (CR) is the disappearance of all target and non-target lesions; partial response (PR) is >=30% decrease in the sum of diameters of target lesions; progressive disease (PD) is >=20% increase in the sum of diameters of target lesions, or a measurable increase in a non-target lesion, or the appearance of >=1 new lesion; stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time Frame	Date of consent until end of study treatment, up to 32 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pazopanib
Arm/Group Description	Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity. pazopanib: Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity.
Measure Participants	41
Complete response	0 0%
Partial Response	2.4 5.9%
Stable Disease	41.5 101.2%
Progressive Disease	43.9 107.1%
Inevaluable	12.2 29.8%

4. Secondary Outcome

Title	Duration of Response
Description	Response is defined as Complete Response (CR) or Partial Response (PR) per RECIST v1.1. Repeat radiologic imaging will be conducted after every 3 cycles of treatment (approximately every 12 weeks) to evaluate disease status per RECIST v1.1. Confirmation of CR or PR is required by repeat scans that should be performed 4 weeks after the criteria for response are first met.
Time Frame	Measure of the amount of time that the criteria for response per RECIST are first met until disease progression

Outcome Measure Data

Analysis Population Description

Since so few patients experienced a response, the pre-specified endpoint of duration of response was not analyzed.

Arm/Group Title	Pazopanib
Arm/Group Description	Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity. pazopanib: Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity.
Measure Participants	0

5. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was measured from date of consent until time of death from any cause, up to 32 months.
Time Frame	Date of Consent until death, up to 32 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pazopanib
Arm/Group Description	Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity. pazopanib: Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity.
Measure Participants	41
Median (95% Confidence Interval) [months]	12.62

Adverse Events

Arm/Group Title	Pazopanib
Arm/Group Description	Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity. pazopanib: Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity.
All Cause Mortality
	Pazopanib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pazopanib
	Affected / at Risk (%)	# Events
Total	17/41 (41.5%)
Blood and lymphatic system disorders
Thrombocytopenia	1/41 (2.4%)
Gastrointestinal disorders
Abdominal Pain	1/41 (2.4%)
Gastric Perforation	2/41 (4.9%)
Large Intestine Perforation	1/41 (2.4%)
Lower Gastrointestinal Haemorrhage	1/41 (2.4%)
Small Intestinal Obstruction	1/41 (2.4%)
Upper Gastrointestinal Haemorrhage	1/41 (2.4%)
General disorders
death	2/41 (4.9%)
Fatigue	1/41 (2.4%)
Hepatobiliary disorders
Hepatic Haemorrhage	1/41 (2.4%)
Infections and infestations
Cellulitis	1/41 (2.4%)
Escherichia Sepsis	1/41 (2.4%)
Perirectal Abscess	1/41 (2.4%)
Sepsis	1/41 (2.4%)
Investigations
International Normalised Ratio Increased	1/41 (2.4%)
Metabolism and nutrition disorders
Dehydration	1/41 (2.4%)
Nervous system disorders
Depressed Level Of Consciousness	1/41 (2.4%)
Dizziness	1/41 (2.4%)
Transient Ischaemic Attack	1/41 (2.4%)
Psychiatric disorders
Mental Disorder Due To A General Medical Condition	1/41 (2.4%)
Renal and urinary disorders
Acute Kidney Injury	1/41 (2.4%)
Respiratory, thoracic and mediastinal disorders
Aspiration	1/41 (2.4%)
Dyspnoea	1/41 (2.4%)
Other (Not Including Serious) Adverse Events
	Pazopanib
	Affected / at Risk (%)	# Events
Total	39/41 (95.1%)
Blood and lymphatic system disorders
Anaemia	7/41 (17.1%)
Leukopenia	1/41 (2.4%)
Neutropenia	1/41 (2.4%)
Thrombocytopenia	2/41 (4.9%)
Cardiac disorders
Atrial Fibrillation	1/41 (2.4%)
Cardiac Failure Congestive	1/41 (2.4%)
Palpitations	1/41 (2.4%)
Sinus Tachycardia	1/41 (2.4%)
Ear and labyrinth disorders
Tinnitus	1/41 (2.4%)
Vertigo	1/41 (2.4%)
Endocrine disorders
Hyperthyroidism	1/41 (2.4%)
Hypothyroidism	8/41 (19.5%)
Eye disorders
Exfoliation Syndrome	1/41 (2.4%)
Exophthalmos	1/41 (2.4%)
Eye Swelling	1/41 (2.4%)
Periorbital Oedema	1/41 (2.4%)
Scleral Disorder	2/41 (4.9%)
Vision Blurred	2/41 (4.9%)
Gastrointestinal disorders
Abdominal Distension	3/41 (7.3%)
Abdominal Pain	9/41 (22%)
Abdominal Pain Lower	2/41 (4.9%)
Abdominal Pain Upper	4/41 (9.8%)
Colonic Fistula	1/41 (2.4%)
Constipation	5/41 (12.2%)
Dental Caries	2/41 (4.9%)
Diarrhoea	14/41 (34.1%)
Dry Mouth	2/41 (4.9%)
Dysphagia	1/41 (2.4%)
Flatulence	2/41 (4.9%)
Gastrointestinal Fistula	1/41 (2.4%)
Gastrointestinal Motility Disorder	1/41 (2.4%)
Gastrooesophageal Reflux Disease	2/41 (4.9%)
Haemorrhoids	1/41 (2.4%)
Ileus	1/41 (2.4%)
Impaired Gastric Emptying	1/41 (2.4%)
Large Intestinal Ulcer Haemorrhage	1/41 (2.4%)
Nausea	16/41 (39%)
Proctalgia	2/41 (4.9%)
Proctitis	1/41 (2.4%)
Rectal Haemorrhage	1/41 (2.4%)
Stomatitis	3/41 (7.3%)
Toothache	1/41 (2.4%)
Vomiting	8/41 (19.5%)
General disorders
Asthenia	1/41 (2.4%)
Chest Pain	1/41 (2.4%)
Early Satiety	1/41 (2.4%)
Fatigue	12/41 (29.3%)
Localised Oedema	1/41 (2.4%)
Non-Cardiac Chest Pain	1/41 (2.4%)
Oedema Peripheral	5/41 (12.2%)
Pain	1/41 (2.4%)
Peripheral Swelling	2/41 (4.9%)
Pyrexia	1/41 (2.4%)
Temperature Intolerance	1/41 (2.4%)
Infections and infestations
Diverticulitis	1/41 (2.4%)
Gastrointestinal Infection	1/41 (2.4%)
Herpes Zoster	1/41 (2.4%)
Nail Infection	1/41 (2.4%)
Pneumonia	1/41 (2.4%)
Septic Shock	1/41 (2.4%)
Skin Infection	2/41 (4.9%)
Upper Respiratory Tract Infection	1/41 (2.4%)
Urinary Tract Infection	4/41 (9.8%)
Injury, poisoning and procedural complications
Fall	2/41 (4.9%)
Stress Fracture	1/41 (2.4%)
Subdural Haematoma	1/41 (2.4%)
Transfusion Reaction	1/41 (2.4%)
Investigations
Activated Partial Thromboplastin Time Prolonged	1/41 (2.4%)
Alanine Aminotransferase Increased	3/41 (7.3%)
Aspartate Aminotransferase Increased	2/41 (4.9%)
Blood Bilirubin Increased	1/41 (2.4%)
Blood Creatinine Increased	4/41 (9.8%)
Blood Culture Positive	1/41 (2.4%)
Blood Thyroid Stimulating Hormone Increased	2/41 (4.9%)
Electrocardiogram QT Prolonged	1/41 (2.4%)
Gastrointestinal Infection	1/41 (2.4%)
International Normalised Ratio Increased	1/41 (2.4%)
Lipase Increased	1/41 (2.4%)
Neutrophil Count Decreased	2/41 (4.9%)
Platelet Count Decreased	7/41 (17.1%)
Prothrombin Time Prolonged	1/41 (2.4%)
Troponin I Increased	1/41 (2.4%)
Urine Output Decreased	1/41 (2.4%)
Urine Protein/Creatinine Ratio	3/41 (7.3%)
Weight Decreased	7/41 (17.1%)
Metabolism and nutrition disorders
Decreased Appetite	7/41 (17.1%)
Hyperkalaemia	2/41 (4.9%)
Hyperuricaemia	1/41 (2.4%)
Hypoalbuminaemia	5/41 (12.2%)
Hypoglycaemia	1/41 (2.4%)
Hypokalaemia	7/41 (17.1%)
Hypomagnesaemia	2/41 (4.9%)
Hyponatraemia	4/41 (9.8%)
Hypophosphataemia	4/41 (9.8%)
Iron Deficiency	1/41 (2.4%)
Metabolic Acidosis	2/41 (4.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/41 (4.9%)
Back Pain	4/41 (9.8%)
Fistula	1/41 (2.4%)
Flank Pain	1/41 (2.4%)
Muscle Spasms	1/41 (2.4%)
Muscular Weakness	1/41 (2.4%)
Musculoskeletal Pain	2/41 (4.9%)
Musculoskeletal Stiffness	1/41 (2.4%)
Myalgia	2/41 (4.9%)
Pain In Extremity	4/41 (9.8%)
Pathological Fracture	1/41 (2.4%)
Tendonitis	1/41 (2.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Salivary Gland Adenoma	1/41 (2.4%)
Nervous system disorders
Aphasia	1/41 (2.4%)
Disturbance In Attention	1/41 (2.4%)
Dizziness	7/41 (17.1%)
Dysgeusia	6/41 (14.6%)
Headache	2/41 (4.9%)
Hypoaesthesia	1/41 (2.4%)
Memory Impairment	1/41 (2.4%)
Metabolic Encephalopathy	1/41 (2.4%)
Neuralgia	1/41 (2.4%)
Paraesthesia	1/41 (2.4%)
Peripheral Sensory Neuropathy	1/41 (2.4%)
Syncope	1/41 (2.4%)
Vocal Cord Paralysis	1/41 (2.4%)
Psychiatric disorders
Agitation	1/41 (2.4%)
Anxiety	1/41 (2.4%)
Confusional State	1/41 (2.4%)
Depression	1/41 (2.4%)
Insomnia	3/41 (7.3%)
Restlessness	1/41 (2.4%)
Renal and urinary disorders
Pollakiuria	2/41 (4.9%)
Proteinuria	1/41 (2.4%)
Urinary Incontinence	1/41 (2.4%)
Reproductive system and breast disorders
Testicular Swelling	1/41 (2.4%)
Vaginal Haemorrhage*f	1/14 (7.1%)
Vulvovaginal Dryness*f	2/14 (14.3%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	1/41 (2.4%)
Cough	3/41 (7.3%)
Dysphonia	1/41 (2.4%)
Dyspnoea	3/41 (7.3%)
Epistaxis	1/41 (2.4%)
Hiccups	1/41 (2.4%)
Oropharyngeal Pain	1/41 (2.4%)
Pleural Effusion	2/41 (4.9%)
Respiratory Failure	1/41 (2.4%)
Rhinitis Allergic	3/41 (7.3%)
Rhinorrhoea	1/41 (2.4%)
Skin and subcutaneous tissue disorders
Alopecia	1/41 (2.4%)
Dermatitis	1/41 (2.4%)
Dry Skin	2/41 (4.9%)
Erythema	1/41 (2.4%)
Erythema Multiforme	2/41 (4.9%)
Granulomatous Dermatitis	1/41 (2.4%)
Hair Colour Changes	3/41 (7.3%)
Intertrigo	1/41 (2.4%)
Nail Discolouration	1/41 (2.4%)
Palmar-Plantar Erythrodysaesthesia Syndrome	5/41 (12.2%)
Pruritus	4/41 (9.8%)
Rash	3/41 (7.3%)
Rash Macular	1/41 (2.4%)
Rash Papular	1/41 (2.4%)
Skin Exfoliation	2/41 (4.9%)
Skin Exfoliation*m	1/27 (3.7%)
Skin Hypopigmentation	3/41 (7.3%)
Skin Mass	1/41 (2.4%)
Skin Necrosis	1/41 (2.4%)
Skin Ulcer	3/41 (7.3%)
Stasis Dermatitis	1/41 (2.4%)
Urticaria	1/41 (2.4%)
Vascular disorders
Deep Vein Thrombosis	2/41 (4.9%)
Hypertension	15/41 (36.6%)
Hypotension	3/41 (7.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Institution/PI may use Institution/PI derived Study results in a Publication provided Publication does not disclose Vector Confidential Information unnecessary to publish Study results. Institution/PI will submit to Vector for review/comment proposed Publication and data necessary for meaningful review at least 30 days prior to submission. Vector may request delay of submission up to 60 days in order to file patent applications relating to an Invention.