LAPC: Dasatinib Added to Gemcitabine for Subjects With Locally-advanced Pancreatic Cancer

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01395017
• Collaborator: (none)
• Enrollment: 202
• Locations: 77
• Arms: 2
• Duration (Months): 45
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether patients with locally advanced pancreatic cancer who receive dasatinib added to standard of care (gemcitabine) live longer, compared to patients who receive standard of care (gemcitabine) plus placebo; i.e. gemcitabine alone.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Drug: dasatinib; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 202 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Placebo-controlled Double-blind Trial of Dasatinib Added to Gemcitabine for Subjects With Locally-advanced Pancreatic Cancer
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group 1 One arm will receive standard of care treatment (ie, GEM 1000 mg/m2 by intravenous [IV] infusion weekly for 3 weeks of a 4-week cycle) plus dasatinib 100 mg by mouth once daily (QD).	Drug: dasatinib; GEM 1000 mg/m2 by intravenous [IV] infusion weekly for 3 weeks of a 4-week cycle plus dasatinib 100 mg (or matched placebo) by mouth once daily (QD). Subjects will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.; Other Names: BMS-354825
Placebo Comparator: Group 2 The other arm will receive standard of care treatment (ie, GEM 1000 mg/m2 by intravenous [IV] infusion weekly for 3 weeks of a 4-week cycle) plus matched placebo by mouth once daily (QD).	Drug: Placebo; Matching Placebo

Outcome Measures

Primary Outcome Measures

1. Overall Survival [From randomization until date of death from any cause by 02 December 2013]

   Overall survival (OS) is the time from randomization until time of death from any cause by 02 December 2013.

Secondary Outcome Measures

1. Progression Free Survival (PFS) [Time from randomization to earliest PFS event by 02 December 2013]

   PFS - time from randomization to unequivocal local or distant disease progression, death or discontinuation from trial for any reason by 02 December 2013. Progression events were determined according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 every 8 weeks.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologic or cytologic documentation of unresectable adenocarcinoma of the pancreas.

• Recovery from toxicity of previous procedures to establish the diagnosis. ECOG PS 0 or

• Adequate organ function.

Exclusion Criteria:

• Evidence of metastatic disease.

• Previous radiotherapy or chemoradiotherapy.

• History of or current pleural effusion.

• History of significant cardiovascular disease.

• Clinically significant bleeding disorder or coagulopathy.

• Concomitant medication with strong CYP 3A4 inhibitor.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States	35249
2		Los Angeles	California	United States	90095
3		Orange	California	United States	92868
4		San Francisco	California	United States	94115
5		Aurora	Colorado	United States	80045
6		Boynton Beach	Florida	United States	33426
7		Tampa	Florida	United States	33606
8		Wichita	Kansas	United States	67214
9		Minneapolis	Minnesota	United States	55455
10		Albuquerque	New Mexico	United States	87131
11		Bethlehem	Pennsylvania	United States	18015
12		Blacktown	New South Wales	Australia	2148
13		Liverpool	New South Wales	Australia	2170
14		Tweed Heads	New South Wales	Australia	2485
15		Footscray	Victoria	Australia	3011
16		Frankston	Victoria	Australia	3199
17		Parkville	Victoria	Australia	3050
18		Wien		Austria	1090
19		Brussels		Belgium	1200
20		Gent		Belgium	9000
21		Leuven		Belgium	3000
22		Toronto	Ontario	Canada	M4N 3M5
23		Toronto	Ontario	Canada	M5G 2M9
24		Montreal	Quebec	Canada	H2X 3J4
25		Olomouc		Czech Republic	77520
26		Pardubice		Czech Republic	532 03
27		Prague 8		Czech Republic	180 81
28		Zlin		Czech Republic	76275
29		Clermont Ferrand cedex 1	Auvergne	France	63003
30		Paris	Cedex 14	France	75674
31		Saint-Priest-en-Jarez	Loire	France	42271
32		Angers	Maine-et-Loire	France	49933
33		Besançon cedex		France	25030
34		Clichy		France	92110
35		Lille		France	59037
36		Lyon cedex 03		France	69437
37		Saint-Priest-en-Jarez cedex 2		France	42277
38		Tübingen	Baden-Württemberg	Germany	72076
39		Hamburg		Germany	20249
40		Köln		Germany	50937
41		München		Germany	81925
42		Pecs	Baranya	Hungary	7624
43		Budapest		Hungary	1097
44		Budapest		Hungary	1122
45		Gyor		Hungary	9024
46		Dublin 24		Ireland
47		Dublin 4		Ireland
48		Dublin 7		Ireland
49		Dublin 9		Ireland
50		Milan	MI	Italy	20133
51		Udine	UD	Italy	33100
52		Ancona		Italy	60020
53		Reggio Emilia		Italy	42100
54		Jelenia Gora		Poland	58-506
55		Lublin		Poland	20-090
56		Olsztyn		Poland	10-228
57		Craiova	Dolj	Romania	200385
58		Bucharest		Romania	022328
59		Cluj-Napoca		Romania	400015
60		Kazan	Tatarstan Republic	Russian Federation	420029
61		Chelyabinsk		Russian Federation	454087
62		Krasnodar		Russian Federation	350040
63		Moscow		Russian Federation	115478
64		Voronezh		Russian Federation	394000
65		Hull	East Yorks	United Kingdom	HU16 5JQ
66		Chelmsford	Essex	United Kingdom	CM1 7ET
67		Maidstone	Kent	United Kingdom	ME16 9QQ
68		Northwood	Middlesex	United Kingdom	HA6 2RN
69		Sutton	Surrey	United Kingdom	SM2 5PT
70		Leeds	West Yorkshire	United Kingdom	LS9 7TF
71		Edinburgh		United Kingdom	EH4 2XU
72		Glasgow		United Kingdom	G12 OYN
73		Liverpool		United Kingdom	L69 3GA
74		London		United Kingdom	SW3 6JJ
75		London		United Kingdom	W12 0HS
76		Salisbury		United Kingdom	SP2 8BJ
77		Wirral		United Kingdom	CH63 4JY

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT01395017
• Other Study ID Numbers: 287-11-201
• First Posted: Jul 15, 2011
• Last Update Posted: Apr 8, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.: Pancreatic cancer; Dasatinib; chemotherapy; Locally advanced
• Additional relevant MeSH terms: Pancreatic Neoplasms; Dasatinib

Study Results

Participant Flow

Recruitment Details	202 participants were enrolled at 79 study sites in 15 countries.
Pre-assignment Detail	Participants were randomly assigned in a 1:1 ratio to receive dasatinib + gemcitabine (GEM) or placebo + GEM. Participants were stratified at the time of randomization by baseline Eastern Cooperative Oncology Group performance status (ECOG PS) (0 versus 1) and intent to receive radiotherapy (RT) (yes or no).

Arm/Group Title	Dasatinib + GEM	Placebo + GEM
Arm/Group Description	GEM 1000 mg/m2 by intravenous (IV) infusion weekly for 3 weeks of a 4-week cycle plus dasatinib 100 mg by mouth once daily (QD).	GEM 1000 mg/m2 by IV infusion weekly for 3 weeks of a 4-week cycle plus matched placebo by mouth QD.
Period Title: Overall Study
STARTED	100	102
Treated	98	101
COMPLETED	0	0
NOT COMPLETED	100	102

Baseline Characteristics

Arm/Group Title	Dasatinib + GEM	Placebo + GEM	Total
Arm/Group Description	GEM 1000 mg/m2 by IV infusion weekly for 3 weeks of a 4-week cycle plus dasatinib 100 mg by mouth QD.	GEM 1000 mg/m2 by IV infusion weekly for 3 weeks of a 4-week cycle plus matched placebo by mouth QD.	Total of all reporting groups
Overall Participants	100	102	202
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.8 (9.1)	64.7 (9.6)	64.8 (9.4)
Sex: Female, Male (Count of Participants)
Female	43 43%	56 54.9%	99 49%
Male	57 57%	46 45.1%	103 51%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Overall survival (OS) is the time from randomization until time of death from any cause by 02 December 2013.
Time Frame	From randomization until date of death from any cause by 02 December 2013

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) data which was composed of all randomized participants.

Arm/Group Title	Dasatinib + GEM	Placebo + GEM
Arm/Group Description	GEM 1000 mg/m2 by IV infusion weekly for 3 weeks of a 4-week cycle plus dasatinib 100 mg by mouth QD	GEM 1000 mg/m2 by IV infusion weekly for 3 weeks of a 4-week cycle plus matched placebo by mouth QD.
Measure Participants	100	102
Median (95% Confidence Interval) [Days]	375	393

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dasatinib + GEM, Placebo + GEM
	Comments	Using a 1-sided alpha=0.2, a population of 200 participants (100 GEM plus dasatinib and 100 GEM plus placebo) has 79% power to show an increase in median OS from 10 to 13.3 months (hazard ratio [HR] =0.75, assuming analysis of 135 deaths).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3864
	Comments	The log-rank test was used to test OS. As a sensitivity analysis, HR and its confidence interval was also provided for OS using the Cox proportional hazard model.
	Method	Cox proportional hazard model
	Comments	Adjusting for baseline factors - treatment, ECOG PS, region, CA19-9 level (< 1000 IU/mL or >/=1000 IU/mL), and RT during trial (yes or no).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS - time from randomization to unequivocal local or distant disease progression, death or discontinuation from trial for any reason by 02 December 2013. Progression events were determined according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 every 8 weeks.
Time Frame	Time from randomization to earliest PFS event by 02 December 2013

Outcome Measure Data

Analysis Population Description

The ITT data which was composed of all randomized participants.

Arm/Group Title	Dasatinib + GEM	Placebo + GEM
Arm/Group Description	GEM 1000 mg/m2 by IV infusion weekly for 3 weeks of a 4-week cycle plus dasatinib 100 mg by mouth QD.	GEM 1000 mg/m2 by IV infusion weekly for 3 weeks of a 4-week cycle plus matched placebo by mouth QD.
Measure Participants	100	102
Median (95% Confidence Interval) [Days]	167	166

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dasatinib + GEM, Placebo + GEM
	Comments	Trial has 88% power to show a median PFS increase from 5 to 7 months (with 1-sided alpha=0.15, total 176 events, HR=0.714).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6761
	Comments	The log-rank test was used to test PFS. As a sensitivity analysis, HR and its confidence interval was also provided for PFS using the Cox proportional hazard model.
	Method	Cox proportional hazard model
	Comments	Adjusting for baseline factors: treatment, ECOG PS, region, CA19-9 level (< 1000 IU/mL or >/=1000 IU/mL), and RT during trial (yes or no).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse events (AEs) were collected from randomization, throughout each treatment cycle to final study visit. Follow-up visits conducted until all ongoing AEs resolved or clinically stable.
Adverse Event Reporting Description	The safety data set (participants who received at least one dose of study treatment) included 98 participants in the Dasatinib + GEM group and 101 participants in the placebo + GEM group.
Arm/Group Title	Dasatinib + GEM		Placebo + GEM
Arm/Group Description	GEM 1000 mg/m2 by IV infusion weekly for 3 weeks of a 4-week cycle plus dasatinib 100 mg by mouth QD		GEM 1000 mg/m2 by IV infusion weekly for 3 weeks of a 4-week cycle plus matched placebo by mouth QD.
All Cause Mortality
	Dasatinib + GEM		Placebo + GEM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dasatinib + GEM		Placebo + GEM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/98 (54.1%)		48/101 (47.5%)
Blood and lymphatic system disorders
Anemia	3/98 (3.1%)		1/101 (1%)
Cardiac disorders
Arrhythmia	0/98 (0%)		1/101 (1%)
Atrial fibrillation	0/98 (0%)		1/101 (1%)
Cardiac arrest	0/98 (0%)		1/101 (1%)
Cardiac failure	4/98 (4.1%)		2/101 (2%)
Cardiac failure acute	1/98 (1%)		0/101 (0%)
Cardiac failure congestive	1/98 (1%)		0/101 (0%)
Cardio-respiratory arrest	0/98 (0%)		1/101 (1%)
Cardiomyopathy	1/98 (1%)		0/101 (0%)
Sick sinus syndrome	1/98 (1%)		0/101 (0%)
Congenital, familial and genetic disorders
Pyloric stenosis	0/98 (0%)		1/101 (1%)
Gastrointestinal disorders
Abdominal pain	3/98 (3.1%)		1/101 (1%)
Abdominal pain upper	1/98 (1%)		1/101 (1%)
Ascites	2/98 (2%)		2/101 (2%)
Constipation	2/98 (2%)		0/101 (0%)
Diarrhoea	3/98 (3.1%)		0/101 (0%)
Duodenal stenosis	0/98 (0%)		0/101 (0%)
Duodenal ulcer perforation	0/98 (0%)		1/101 (1%)
Duodenitis	1/98 (1%)		0/101 (0%)
Enteritis	0/98 (0%)		1/101 (1%)
Intestinal obstruction	1/98 (1%)		1/101 (1%)
Nausea	1/98 (1%)		0/101 (0%)
Obstruction gastric	3/98 (3.1%)		1/101 (1%)
Pancreatic necrosis	1/98 (1%)		0/101 (0%)
Small intestine obstruction	0/98 (0%)		1/101 (1%)
Vomiting	3/98 (3.1%)		2/101 (2%)
General disorders
Asthenia	0/98 (0%)		1/101 (1%)
Device occlusion	5/98 (5.1%)		5/101 (5%)
General physical health deterioration	0/98 (0%)		1/101 (1%)
Generalised oedema	1/98 (1%)		0/101 (0%)
Hyperthermia	0/98 (0%)		1/101 (1%)
Multi-organ failure	1/98 (1%)		0/101 (0%)
Oedema	1/98 (1%)		0/101 (0%)
Oedema peripheral	3/98 (3.1%)		0/101 (0%)
Pyrexia	1/98 (1%)		4/101 (4%)
Stent malfunction	0/98 (0%)		1/101 (1%)
Sudden death	0/98 (0%)		1/101 (1%)
Hepatobiliary disorders
Bile duct obstruction	4/98 (4.1%)		2/101 (2%)
Bile duct stenosis	2/98 (2%)		0/101 (0%)
Cholangitis	4/98 (4.1%)		2/101 (2%)
Cholecystitis	1/98 (1%)		2/101 (2%)
Cholecystitis acute	1/98 (1%)		0/101 (0%)
Hepatotoxicity	0/98 (0%)		1/101 (1%)
Hyperbilirubinaemia	5/98 (5.1%)		1/101 (1%)
Jaundice	0/98 (0%)		1/101 (1%)
Jaundice cholestatic	2/98 (2%)		0/101 (0%)
Infections and infestations
Abdominal abscess	0/98 (0%)		1/101 (1%)
Abscess	0/98 (0%)		1/101 (1%)
Bacteraemia	1/98 (1%)		0/101 (0%)
Biliary sepsis	1/98 (1%)		0/101 (0%)
Biliary tract infection	2/98 (2%)		0/101 (0%)
Bronchitis	1/98 (1%)		0/101 (0%)
Cellulitis	2/98 (2%)		0/101 (0%)
Device related infection	0/98 (0%)		1/101 (1%)
Escherichia infection	1/98 (1%)		0/101 (0%)
Escherichia sepsis	1/98 (1%)		0/101 (0%)
Infective exacerbation of chronic obstructive airways disease	0/98 (0%)		1/101 (1%)
Liver abcess	1/98 (1%)		1/101 (1%)
Lower respiratory tract infection	0/98 (0%)		1/101 (1%)
Lung infection	1/98 (1%)		0/101 (0%)
Peritonitis	0/98 (0%)		1/101 (1%)
Pneumonia	3/98 (3.1%)		1/101 (1%)
Sepsis	2/98 (2%)		1/101 (1%)
Streptococcal infection	1/98 (1%)		0/101 (0%)
Urinary tract infection	3/98 (3.1%)		0/101 (0%)
Viral infection	1/98 (1%)		1/101 (1%)
Injury, poisoning and procedural complications
Accidental overdose	1/98 (1%)		0/101 (0%)
Chemical peritonitis	0/98 (0%)		1/101 (1%)
Fall	1/98 (1%)		0/101 (0%)
Gastrointestinal stoma complication	1/98 (1%)		0/101 (0%)
Head injury	1/98 (1%)		0/101 (0%)
Post procedural bile leak	0/98 (0%)		1/101 (1%)
Spinal compression fracture	0/98 (0%)		1/101 (1%)
Investigations
Hepatic enzyme increased	0/98 (0%)		1/101 (1%)
Liver function test abnormal	1/98 (1%)		0/101 (0%)
Platelet count decreased	1/98 (1%)		0/101 (0%)
Metabolism and nutrition disorders
Dehydration	2/98 (2%)		1/101 (1%)
Diabetes mellitus	1/98 (1%)		0/101 (0%)
Failure to thrive	2/98 (2%)		0/101 (0%)
Fluid retention	1/98 (1%)		0/101 (0%)
Hypoglycaemia	0/98 (0%)		2/101 (2%)
Hypokalaemia	1/98 (1%)		0/101 (0%)
Malnutrition	1/98 (1%)		0/101 (0%)
Musculoskeletal and connective tissue disorders
Osteonecrosis	1/98 (1%)		0/101 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	2/98 (2%)		1/101 (1%)
Metastases to bone	0/98 (0%)		1/101 (1%)
Tumour haemorrhage	0/98 (0%)		1/101 (1%)
Psychiatric disorders
Confusional state	0/98 (0%)		1/101 (1%)
Depression	1/98 (1%)		0/101 (0%)
Renal and urinary disorders
Renal failure	1/98 (1%)		0/101 (0%)
Renal failure acute	1/98 (1%)		0/101 (0%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/98 (1%)		1/101 (1%)
Acute respiratory failure	0/98 (0%)		1/101 (1%)
Asthmatic crisis	1/98 (1%)		0/101 (0%)
Chronic obstructive pulmonary disease	1/98 (1%)		0/101 (0%)
Dyspnoea	2/98 (2%)		1/101 (1%)
Dyspnoea exertional	1/98 (1%)		0/101 (0%)
Interstitial lung disease	0/98 (0%)		1/101 (1%)
Lung disorder	0/98 (0%)		1/101 (1%)
Pleural effusion	6/98 (6.1%)		2/101 (2%)
Pneumothorax	0/98 (0%)		1/101 (1%)
Pulmonary arterial hypertension	1/98 (1%)		0/101 (0%)
Pulmonary embolism	0/98 (0%)		1/101 (1%)
Pulmonary fibrosis	0/98 (0%)		1/101 (1%)
Respiratory failure	0/98 (0%)		1/101 (1%)
Skin and subcutaneous tissue disorders
Erythema	1/98 (1%)		0/101 (0%)
Necrolytic migratory erythema	1/98 (1%)		0/101 (0%)
Toxic skin eruption	0/98 (0%)		1/101 (1%)
Vascular disorders
Deep vein thrombosis	0/98 (0%)		1/101 (1%)
Hypertension	0/98 (0%)		1/101 (1%)
Hypotension	0/98 (0%)		1/101 (1%)
Thrombosis	1/98 (1%)		0/101 (0%)
Venous thrombosis	0/98 (0%)		1/101 (1%)
Other (Not Including Serious) Adverse Events
	Dasatinib + GEM		Placebo + GEM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	93/98 (94.9%)		98/101 (97%)
Blood and lymphatic system disorders
Anemia	50/98 (51%)		28/101 (27.7%)
Leukopenia	8/98 (8.2%)		13/101 (12.9%)
Lymphopenia	5/98 (5.1%)		7/101 (6.9%)
Neutropenia	53/98 (54.1%)		49/101 (48.5%)
Thrombocytopenia	38/98 (38.8%)		39/101 (38.6%)
Gastrointestinal disorders
Abdominal pain	33/98 (33.7%)		36/101 (35.6%)
Abdominal pain upper	10/98 (10.2%)		18/101 (17.8%)
Ascites	8/98 (8.2%)		6/101 (5.9%)
Constipation	33/98 (33.7%)		28/101 (27.7%)
Diarrhoea	41/98 (41.8%)		29/101 (28.7%)
Dry mouth	5/98 (5.1%)		6/101 (5.9%)
Dyspepsia	9/98 (9.2%)		7/101 (6.9%)
Flatulence	6/98 (6.1%)		11/101 (10.9%)
Nausea	65/98 (66.3%)		49/101 (48.5%)
Stomatitis	9/98 (9.2%)		8/101 (7.9%)
Vomiting	40/98 (40.8%)		34/101 (33.7%)
General disorders
Asthenia	17/98 (17.3%)		16/101 (15.8%)
Chest pain	2/98 (2%)		7/101 (6.9%)
Chills	6/98 (6.1%)		4/101 (4%)
Face oedema	5/98 (5.1%)		1/101 (1%)
Fatigue	50/98 (51%)		46/101 (45.5%)
Oedema peripheral	32/98 (32.7%)		22/101 (21.8%)
Pain	2/98 (2%)		8/101 (7.9%)
Pyrexia	22/98 (22.4%)		27/101 (26.7%)
Hepatobiliary disorders
Hyperbilirubinaemia	3/98 (3.1%)		7/101 (6.9%)
Infections and infestations
Nasopharyngitis	7/98 (7.1%)		5/101 (5%)
Oral candidiasis	7/98 (7.1%)		5/101 (5%)
Upper respiratory tract infection	7/98 (7.1%)		3/101 (3%)
Urinary tract infection	6/98 (6.1%)		1/101 (1%)
Investigations
Alanine aminotransferase increased	22/98 (22.4%)		14/101 (13.9%)
Aspartate aminotransferase increased	16/98 (16.3%)		11/101 (10.9%)
Blood alkalne phosphatase increased	15/98 (15.3%)		8/101 (7.9%)
Blood bilirubin increased	13/98 (13.3%)		6/101 (5.9%)
Gamma glutamyltransferase increased	5/98 (5.1%)		1/101 (1%)
Haemaglobin decreased	5/98 (5.1%)		6/101 (5.9%)
Neutrophil count decreased	6/98 (6.1%)		5/101 (5%)
Platelet count decreased	7/98 (7.1%)		4/101 (4%)
Weight decreased	21/98 (21.4%)		11/101 (10.9%)
White blood cell count decreased	8/98 (8.2%)		2/101 (2%)
Metabolism and nutrition disorders
Decreased appetite	48/98 (49%)		23/101 (22.8%)
Hyperglycaemia	9/98 (9.2%)		6/101 (5.9%)
Hypokalaemia	12/98 (12.2%)		10/101 (9.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/98 (3.1%)		6/101 (5.9%)
Back pain	8/98 (8.2%)		16/101 (15.8%)
Muscloskeletal pain	1/98 (1%)		6/101 (5.9%)
Pain in extremity	10/98 (10.2%)		5/101 (5%)
Nervous system disorders
Dizziness	4/98 (4.1%)		11/101 (10.9%)
Dysgeusia	12/98 (12.2%)		6/101 (5.9%)
Headache	12/98 (12.2%)		9/101 (8.9%)
Psychiatric disorders
Anxiety	10/98 (10.2%)		4/101 (4%)
Depression	6/98 (6.1%)		5/101 (5%)
Insomnia	12/98 (12.2%)		14/101 (13.9%)
Respiratory, thoracic and mediastinal disorders
Cough	14/98 (14.3%)		13/101 (12.9%)
Dyspnoea	25/98 (25.5%)		19/101 (18.8%)
Pleural effusion	20/98 (20.4%)		5/101 (5%)
Skin and subcutaneous tissue disorders
Alopecia	10/98 (10.2%)		7/101 (6.9%)
Dry skin	5/98 (5.1%)		3/101 (3%)
Erythema	5/98 (5.1%)		3/101 (3%)
Night sweats	6/98 (6.1%)		2/101 (2%)
Pruritus	6/98 (6.1%)		9/101 (8.9%)
Rash	20/98 (20.4%)		14/101 (13.9%)
Vascular disorders
Hypertension	4/98 (4.1%)		10/101 (9.9%)

Limitations/Caveats

5 participants (who had not experienced disease progression at the time of event-driven data cut-off) were told the study results and were instructed to indicate "sponsor discontinued study" if they did not want to continue in the study.

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Certain Agreements

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

There is NOT 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.