ZELIG: Zactima in Non Small Cell Lung Cancer (NSCLC) ELderly Patients In Combination With or Versus Gemcitabine

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00753714
• Collaborator: (none)
• Enrollment: 124
• Locations: 15
• Arms: 2
• Duration (Months): 38
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of this study is to demonstrate an improvement in Progression-Free Survival (PFS) for the combination of vandetanib plus gemcitabine compared with gemcitabine plus placebo in chemonaïve (not including an adjuvant regimen) patients aged ≥ 70 years with advanced NSCLC.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer	Drug: ZD6474, Vandetanib; Drug: Placebo to Match ZD6474, Vandetanib; Drug: Gemcitabine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 124 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase II, Randomised, Double-blind, Two-arm, Parallel Study of Vandetanib (ZACTIMA™ , ZD6474) Plus Gemcitabine (Gemzar® ) or Gemcitabine Plus Placebo as First Line Treatment of Advanced (Stage IIIB or IV) Non Small Cell Lung Cancer (NSCLC) Elderly Patients.
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1.Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with vandetanib alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued.	Drug: ZD6474, Vandetanib; 100 mg as a once daily oral dose, from Day 1 until disease progression or unacceptable toxicity or consent withdrawal whichever occurs first; Other Names: Zactima ; Drug: Gemcitabine; administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle UP to 6 cycles or UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first; Other Names: Gemzar
Placebo Comparator: B Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1.Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with placebo alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued.	Drug: Placebo to Match ZD6474, Vandetanib; 100 mg as a once daily oral dose, from Day 1 UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first; Other Names: Zactima ; Drug: Gemcitabine; administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle UP to 6 cycles or UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first; Other Names: Gemzar

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [Oct 2008- dec 2011]

Secondary Outcome Measures

1. Overall Survival [Oct 2008- dec 2011]

2. Overall Objective Response [Oct 2008- dec 2011]

3. Duration of Response [Oct 2008- dec 2011]

4. The Safety and Tolerability Profile of ZD6474 (Vandetanib) in Combination With Gemcitabine [Oct 2008- Dec 2011]

   The Safety and Tolerability Profile of ZD6474 (Vandetanib) in Combination With Gemcitabine is defined as the number of Adverse Events which includes any symptoms and/or Clinically Significant Laboratory or Vital Signs Abnormalities, and/or ECGs Changes

Eligibility Criteria

Criteria

• Ages Eligible for Study: 70 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologic or cytologic confirmation of advanced NSCLC (stage IIIB with supraclavicular lymph node metastases or pleural effusion or stage IV) on entry into study

• One or more measurable lesions at least 10 mm in the longest diameter (LD) by spiral CT scan or 20 mm with conventional techniques according to RECIST criteria

• Chemotherapy-naïve (prior chemotherapy in the adjuvant setting completed more than 3 months before the trial entry is accepted).

• Female or male aged 70 years or above

Exclusion Criteria:

• Patients must not have received prior anti-cancer therapy except in the adjuvant setting

• Inadequate end-organ function or Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial

• Significant cardiovascular event (e.g. myocardial infarction, superior vena cava [SVC] syndrome, New York Heart Association [NYHA] classification of heart disease ³2) within 3 months before entry, or presence of cardiac disease that in the opinion of

• History of arrhythmia or QTc with Bazett's correction unmeasurable or ≥ 480 msec on screening ECG

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Meldola	(fc)	Italy
2	Research Site	Avellino	AV	Italy
3	Research Site	Bari	BA	Italy
4	Research Site	Treviglio	BG	Italy
5	Research Site	Bologna	BO	Italy
6	Research Site	Genova	GE	Italy
7	Research Site	Taormina	ME	Italy
8	Research Site	Milano	MI	Italy
9	Research Site	Perugia	PG	Italy
10	Research Site	Ravenna	RA	Italy
11	Research Site	Trento	TN	Italy
12	Research Site	Orbassano	TO	Italy
13	Research Site	Udine	UD	Italy
14	Research Site	Padova		Italy
15	Research Site	Roma		Italy

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

• Gridelli C. Treatment of advanced non small-cell lung cancer in the elderly: from best supportive care to the combination of platin-based chemotherapy and targeted therapies. J Clin Oncol. 2008 Jan 1;26(1):13-5. doi: 10.1200/JCO.2007.14.1820.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT00753714
• Other Study ID Numbers: D4200L00012; EUDRACT n° 2007-004521-22
• First Posted: Sep 16, 2008
• Last Update Posted: Oct 17, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Genzyme, a Sanofi Company: ZD6474; VANDETANIB; ZACTIMA; ADVANCED; NSCLC; LUNG CANCER; ELDERLY PATIENTS; GEMCITABINE; PHASE II; RANDOMIZED; DOUBLE-BLIND; histologically or cytologically-confirmed advanced (stage IIIB with supraclavicular lymph node metastases or pleural effusion or stage IV) NSCLC
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Gemcitabine

Study Results

Participant Flow

Recruitment Details	A total of 124 patients have been enrolled in a period of 19 months in 17 actively recruiting Oncologic Medical Department in Italy.

Arm/Group Title	ZD6474 (Vandetanib),Gemcitabine	Placebo to Match ZD6474 (Vandetanib),Gemcitabine
Arm/Group Description	Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1. Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with vandetanib alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued.	Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1. Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with placebo alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued
Period Title: Overall Study
STARTED	61	63
COMPLETED	1	1
NOT COMPLETED	60	62

Baseline Characteristics

Arm/Group Title	ZD6474 (Vandetanib),Gemcitabine	Placebo to Match ZD6474 (Vandetanib),Gemcitabine	Total
Arm/Group Description	Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1. . Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with vandetanib alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued.	Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1. . Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with placebo alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued.	Total of all reporting groups
Overall Participants	61	63	124
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	75.03 (3.34)	75.48 (3.49)	75.25 (3.41)
Sex: Female, Male (Count of Participants)
Female	16 26.2%	18 28.6%	34 27.4%
Male	45 73.8%	45 71.4%	90 72.6%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival
Time Frame	Oct 2008- dec 2011

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ZD6474 (Vandetanib),Gemcitabine	Placebo to Match ZD6474 (Vandetanib),Gemcitabine
Arm/Group Description	Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1.Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with vandetanib alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued.	Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1. . Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with placebo alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued
Measure Participants	61	63
Median (95% Confidence Interval) [days]	183	169

2. Secondary Outcome

Title	Overall Survival
Time Frame	Oct 2008- dec 2011

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ZD6474 (Vandetanib),Gemcitabine	Placebo to Match ZD6474 (Vandetanib),Gemcitabine
Arm/Group Description	Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1. . Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with vandetanib alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued	Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1. . Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with placebo alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued
Measure Participants	61	63
Median (95% Confidence Interval) [days]	262	305

3. Secondary Outcome

Title	Overall Objective Response
Time Frame	Oct 2008- dec 2011

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ZD6474 ( (Vandetanib),Gemcitabine	Placebo to Match ZD6474 (Vandetanib),Gemcitabine
Arm/Group Description	Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1. . Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with vandetanib alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued.	Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1. . Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with placebo alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued.
Measure Participants	61	63
Number [Participants]	9 14.8%	8 12.7%

4. Secondary Outcome

Title	Duration of Response
Time Frame	Oct 2008- dec 2011

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ZD6474 (Vandetanib),Gemcitabine	Placebo to Match ZD6474 (Vandetanib),Gemcitabine
Arm/Group Description	Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1. . Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with vandetanib alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued	Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1. . Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with placebo alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued
Measure Participants	61	63
Median (95% Confidence Interval) [days]	225	214

5. Secondary Outcome

Title	The Safety and Tolerability Profile of ZD6474 (Vandetanib) in Combination With Gemcitabine
Description	The Safety and Tolerability Profile of ZD6474 (Vandetanib) in Combination With Gemcitabine is defined as the number of Adverse Events which includes any symptoms and/or Clinically Significant Laboratory or Vital Signs Abnormalities, and/or ECGs Changes
Time Frame	Oct 2008- Dec 2011

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ZD6474 (Vandetanib),Gemcitabine	Placebo to Match ZD6474 (Vandetanib),Gemcitabine
Arm/Group Description	Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1. . Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with vandetanib alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued	Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1. . Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with placebo alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued.
Measure Participants	61	63
Number [Adverse Events]	378	381

Adverse Events

Arm/Group Title	ZD6474 (Gemcitabine), Vandetanib		Placebo to Match ZD6474 (Gemcitabine), Vandetanib
Arm/Group Description	Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1. . Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with vandetanib alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued.		Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1. . Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with placebo alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued
All Cause Mortality
	ZD6474 (Gemcitabine), Vandetanib		Placebo to Match ZD6474 (Gemcitabine), Vandetanib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ZD6474 (Gemcitabine), Vandetanib		Placebo to Match ZD6474 (Gemcitabine), Vandetanib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/61 (42.6%)		25/63 (39.7%)
Blood and lymphatic system disorders
Pancytopenia	1/61 (1.6%)		0/63 (0%)
Cardiac disorders
Cardiac Failure Acute	1/61 (1.6%)		0/63 (0%)
Myocardial infarction	1/61 (1.6%)		0/63 (0%)
Pleuropericarditis	1/61 (1.6%)		0/63 (0%)
tachycardia	0/61 (0%)		1/63 (1.6%)
Eye disorders
Eye Disorder	1/61 (1.6%)		0/63 (0%)
Gastrointestinal disorders
Pancreatitis	1/61 (1.6%)		0/63 (0%)
Vomiting	1/61 (1.6%)		0/63 (0%)
Ascites	0/61 (0%)		1/63 (1.6%)
Dysphagia	0/61 (0%)		1/63 (1.6%)
General disorders
Pyrexia	0/61 (0%)		3/63 (4.8%)
Chest Pain	0/61 (0%)		1/63 (1.6%)
Hepatobiliary disorders
Hepatic Cirrhosis	0/61 (0%)		1/63 (1.6%)
Infections and infestations
Pneumonia	2/61 (3.3%)		1/63 (1.6%)
Urinary Tract Infection	1/61 (1.6%)		0/63 (0%)
Injury, poisoning and procedural complications
Femur Fracture	1/61 (1.6%)		0/63 (0%)
Investigations
Weight Decrease	1/61 (1.6%)		0/63 (0%)
Musculoskeletal and connective tissue disorders
Muscoloskeletal Pain	1/61 (1.6%)		0/63 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ear Neoplasm	1/61 (1.6%)		0/63 (0%)
Malignant Melanoma	0/61 (0%)		1/63 (1.6%)
Oesophageal Adenocarcinoma	0/61 (0%)		1/63 (1.6%)
Nervous system disorders
Cerebral Infarction	1/61 (1.6%)		0/63 (0%)
Depressed Level Of Consciuosness	1/61 (1.6%)		0/63 (0%)
Cerebral Ischemia	0/61 (0%)		2/63 (3.2%)
Presyncope	0/61 (0%)		1/63 (1.6%)
Psychiatric disorders
Confusional State	1/61 (1.6%)		1/63 (1.6%)
Renal and urinary disorders
Renal Failure	2/61 (3.3%)		0/63 (0%)
Uraniry Retention	0/61 (0%)		1/63 (1.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/61 (4.9%)		9/63 (14.3%)
Pulmunary embolism	3/61 (4.9%)		3/63 (4.8%)
Pneumonitis	2/61 (3.3%)		0/63 (0%)
Pulmunary Oedema	2/61 (3.3%)		0/63 (0%)
respiratory failure	2/61 (3.3%)		1/63 (1.6%)
acute pulmunary oedema	1/61 (1.6%)		0/63 (0%)
chronic obstructive pulmunary disease	1/61 (1.6%)		0/63 (0%)
Cough	1/61 (1.6%)		0/63 (0%)
Pleural Effusion	1/61 (1.6%)		0/63 (0%)
Pleurisy	1/61 (1.6%)		1/63 (1.6%)
Pneumothorax	1/61 (1.6%)		0/63 (0%)
Respiratory Distress	1/61 (1.6%)		0/63 (0%)
Acute Respiratory Failure	0/61 (0%)		1/63 (1.6%)
Skin and subcutaneous tissue disorders
rash	1/61 (1.6%)		0/63 (0%)
Skin Toxicity	1/61 (1.6%)		0/63 (0%)
Vascular disorders
Infarction	0/61 (0%)		1/63 (1.6%)
Peripheral Ischaemia	0/61 (0%)		1/63 (1.6%)
Vena Cava Thrombosis	0/61 (0%)		1/63 (1.6%)
Other (Not Including Serious) Adverse Events
	ZD6474 (Gemcitabine), Vandetanib		Placebo to Match ZD6474 (Gemcitabine), Vandetanib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/61 (96.7%)		62/63 (98.4%)
Blood and lymphatic system disorders
PLT count decrease	7/61 (11.5%)		9/63 (14.3%)
Neutropenia	12/61 (19.7%)		12/63 (19%)
Anaemia	8/61 (13.1%)		14/63 (22.2%)
Thrombocytopenia	7/61 (11.5%)		4/63 (6.3%)
Alanine Aminotransferase Increased	5/61 (8.2%)		1/63 (1.6%)
Neutrphil Count Decreased	5/61 (8.2%)		2/63 (3.2%)
Aspartate Aminotransferase Inctìreased	4/61 (6.6%)		1/63 (1.6%)
Gastrointestinal disorders
Diarrhoea	9/61 (14.8%)		9/63 (14.3%)
Nausea	7/61 (11.5%)		8/63 (12.7%)
Vomiting	4/61 (6.6%)		7/63 (11.1%)
Constipation	2/61 (3.3%)		4/63 (6.3%)
General disorders
pyrexia	17/61 (27.9%)		17/63 (27%)
Fatigue	14/61 (23%)		15/63 (23.8%)
Asthenia	9/61 (14.8%)		13/63 (20.6%)
Mucosal Inflammation	4/61 (6.6%)		4/63 (6.3%)
Oedema Peripheral	4/61 (6.6%)		12/63 (19%)
Chest Pain	2/61 (3.3%)		15/63 (23.8%)
Metabolism and nutrition disorders
Anorexia	8/61 (13.1%)		17/63 (27%)
Hypokaliemia	2/61 (3.3%)		7/63 (11.1%)
Psychiatric disorders
Depression	3/61 (4.9%)		4/63 (6.3%)
Insomnia	1/61 (1.6%)		4/63 (6.3%)
Respiratory, thoracic and mediastinal disorders
Dispnoea	13/61 (21.3%)		19/63 (30.2%)
Cough	9/61 (14.8%)		10/63 (15.9%)
Pulmunary Embolism	4/61 (6.6%)		3/63 (4.8%)
Respiratory Failure	4/61 (6.6%)		1/63 (1.6%)
Skin and subcutaneous tissue disorders
Rash	15/61 (24.6%)		5/63 (7.9%)
Pruritus	4/61 (6.6%)		2/63 (3.2%)
Vascular disorders
Phlebitis	5/61 (8.2%)		3/63 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.