An Efficacy Study in Gastric and Gastroesophageal Junction Cancer Comparing Ipilimumab Versus Standard of Care Immediately Following First Line Chemotherapy

• ClinicalTrials.gov Identifier: NCT01585987
• Recruitment Status: Completed
• First Posted: April 26, 2012
• Results First Posted: November 18, 2015
• Last Update Posted: May 17, 2016
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Locally Advanced (Unresectable) or Metastatic Adenocarcinoma of the Gastric and Gastro-esophageal Junction
• Interventions: Biological: Ipilimumab; Other: Best Supportive care (BSC)
• Enrollment: 143

Participant Flow

Recruitment Details	Acceptable first-line chemotherapy before randomization to this study for a participant was a regimen containing a fluoropyrimidine agent and a platinum salt. Study initiated July 2012. Primary endpoint July 2014. Study completed April 2015.
Pre-assignment Details	114 enrolled and randomized. 29 enrolled but not randomized to treatment group: 26 no longer met study criteria; 2 withdrew consent, 1 other.

Arm/Group Title	Ipilimumab	All Best Supportive Care (BSC)
Arm/Group Description	Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.	All BSC includes both active and non-active BSC. Active BSC includes the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment. In non-active BSC, the fluoropyrimidine used during lead-in chemotherapy was not continued on study and no other chemotherapy or active treatment was used
Period Title: Randomized
Started	57	57
Completed	57	51
Not Completed	0	6
Reason Not Completed
Withdrawal by Subject	0	4
No longer met criteria	0	2
Period Title: Treated
Started	57	51
Completed	3	2
Not Completed	54	49
Reason Not Completed
Disease Progression	39	36
Study Drug Toxicity	9	5
Adverse Event	3	0
Withdrawal by Subject	1	2
Death	1	0
Lost to Follow-up	0	1
Maximum Clinical Benefit	0	1
Non-Specified	1	2
Subject Request	0	1
Poor/Non-Compliance	0	1

Baseline Characteristics

Arm/Group Title		Ipilimumab	All Best Supportive Care (BSC)	Total
Arm/Group Description		Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.	BSC may include the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment.	Total of all reporting groups
Overall Number of Baseline Participants		57	57	114
Baseline Analysis Population Description		All participants randomized to a treatment arm are summarized.
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	57 participants	57 participants	114 participants
		65.0; (34 to 86)	62.0; (32 to 80)	64.0; (32 to 86)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	57 participants	57 participants	114 participants
Less than (<) 65 years of age		28	35	63
Greater, equal to (>=) 65 years of age		29	22	51
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	57 participants	57 participants	114 participants
	Female	21 36.8%	16 28.1%	37 32.5%
	Male	36 63.2%	41 71.9%	77 67.5%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	57 participants	57 participants	114 participants
Russian Federation		1	1	2
Singapore		1	1	2
Hong Kong		1	0	1
United States		8	6	14
Japan		7	5	12
Taiwan		1	0	1
Poland		0	2	2
Korea, Republic of		21	24	45
Italy		11	8	19
France		3	5	8
Germany		1	0	1
Spain		2	5	7

Outcome Measures

1. Primary Outcome

Title	Immune-related Progression Free Survival (irPFS) as Per Assessment of a Blinded Independent Review Committee (IRC) According to Immune Related Response Criteria (irRC) Guidelines
Description	irPFS is defined as the time between the randomization date and the time of disease progression per irRC or death, whichever occurs first. irRC criteria=Measurable new lesions: incorporated into the tumor burden (eg, added to the index lesions); do not define progression unless the total measurable tumor burden increases by the required amount (25%). New non-measurable lesions: not considered progression if the total measurable tumor burden is stable or shrinking. irPFS was measured in months.
Time Frame	Randomization up to 91 irPFS events (Approximately 19 months )

Outcome Measure Data

Analysis Population Description

All participants who were randomized were summarized.

Arm/Group Title	Ipilimumab	All Best Supportive Care (BSC)
Arm/Group Description:	Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.	BSC may include the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment. All BSC = Active and non-active BSC.
Overall Number of Participants Analyzed	57	57
Median (95% Confidence Interval); Unit of Measure: Months
	2.9240; (1.6100 to 5.1580)	4.8950; (3.4500 to 6.5380)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab, All Best Supportive Care (BSC)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0972
	Comments	Significance level used: 0.2
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.439
	Confidence Interval	(2-Sided) 80%; 1.085 to 1.908
	Estimation Comments	The hazard ratio and its associated two-sided 80% confidence interval (CI) was estimated via a stratified Cox model with treatment arm as the only covariate in the model

2. Secondary Outcome

Title	Progression Free Survival (PFS) Per Modified World Health Organization (mWHO) Criteria
Description	PFS per mWHO was defined as the time between the randomization date and the time of disease progression per mWHO criteria or death, whichever occurred first and was measured in months. mWHO criteria: New lesions always mean progression; Changes in non-measurable lesions contribute in the definitions of Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD).
Time Frame	Randomization up to 91 irPFS events (Approximately 19 months )

Outcome Measure Data

Analysis Population Description

All participants randomized to a treatment group were summarized.

Arm/Group Title	Ipilimumab	All Best Supportive Care (BSC)
Arm/Group Description:	Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.	BSC may include the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment. All BSC = Active and non-active BSC.
Overall Number of Participants Analyzed	57	57
Median (95% Confidence Interval); Unit of Measure: Months
	2.7270; (1.4460 to 2.9570)	4.8950; (3.4500 to 6.0780)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab, All Best Supportive Care (BSC)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0336
	Comments	Significance level used: 0.2
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.588
	Confidence Interval	(2-Sided) 80%; 1.199 to 2.103
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Overall Survival (OS) at Primary Endpoint
Description	OS was defined as the time from the date of randomization until the date of death. For those participants who have not died, OS was censored on the last date the participant was known to be alive.
Time Frame	Randomization up to 91 irPFS events (Approximately 19 months)

Outcome Measure Data

Analysis Population Description

All participants randomized to a treatment group and who received at least one dose of active drug were summarized.

Arm/Group Title	Ipilimumab	All Best Supportive Care (BSC)
Arm/Group Description:	Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.	BSC may include the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment. All BSC = Active and non-active BSC.
Overall Number of Participants Analyzed	57	51
Median (95% Confidence Interval); Unit of Measure: Months
	16.7560; (11.7950 to 23.1290)	12.0570 [1]; (9.3310 to NA)

[1]

Not estimable since the largest observation was censored.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab, All Best Supportive Care (BSC)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6433
	Comments	Significance level used: 0.2
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.874
	Confidence Interval	(2-Sided) 80%; 0.602 to 1.269
	Estimation Comments	HR was based on a stratified Cox proportional hazards model with treatment arm as the only covariate in the model.

4. Secondary Outcome

Title	Overall Survival (OS) at Study Completion
Description	OS was defined as the time from the date of randomization until the date of death. For those participants who have not died, OS was censored on the last date the participant was known to be alive.
Time Frame	Randomization up to end of study, April 2015 (Approximately 28 months)

Outcome Measure Data

Analysis Population Description

All participants randomized to a treatment group and who received at least one dose of active drug were summarized.

Arm/Group Title	Ipilimumab	All Best Supportive Care (BSC)
Arm/Group Description:	Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.	BSC may include the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment. All BSC = Active and non-active BSC.
Overall Number of Participants Analyzed	57	57
Median (95% Confidence Interval); Unit of Measure: Months
	12.68; (10.51 to 18.92)	12.06 [1]; (9.33 to NA)

[1]

Upper limit was not estimable.

5. Secondary Outcome

Title	Percentage of Participants With Immune-Related Best Overall Response (irBOR)
Description	IrBOR rate was defined as the number of participants whose Immune-related Best Overall Response (irBOR) criteria was Immune-related Complete Response (irCR) or Immune-related Partial Response (irPR), divided by the total number of participants. The immune-related sum of products of diameters (irSPD) incorporates - in addition to the index lesions - measurable new lesions that may have developed on-study, providing an assessment that includes both index and new lesions. irCR=Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR=A 50% or greater decrease, relative to baseline of the irSPD, (based on irSPD of all index lesions and any measurable new lesions).
Time Frame	Randomization up to 91 irPFS events (Approximately 19 months)

Outcome Measure Data

Analysis Population Description

All participants randomized to a treatment group were summarized.

Arm/Group Title	Ipilimumab	All Best Supportive Care (BSC)
Arm/Group Description:	Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.	BSC may include the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment. All BSC = Active and non-active BSC.
Overall Number of Participants Analyzed	57	57
Measure Type: Number; Unit of Measure: percentage of participants
	1.8	7.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab, All Best Supportive Care (BSC)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3686
	Comments	Significance level used: 0.2
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.0549
	Confidence Interval	(2-Sided) 80%; 0.7009 to 47.6447
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Randomization to end of study (April 2015)
Adverse Event Reporting Description	Study initiated: July 2012; End of Study: April 2015
Arm/Group Title	Ipilimumab	Active Best Supportive Care (BSC)	Non-Active BSC
Arm/Group Description	Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.	Active BSC includes the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization)	Non-Active BSC involves supportive care with cessation of chemotherapy (no active drug)
All-Cause Mortality
	Ipilimumab	Active Best Supportive Care (BSC)	Non-Active BSC
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	Ipilimumab	Active Best Supportive Care (BSC)	Non-Active BSC
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	31/57 (54.39%)	19/45 (42.22%)	1/6 (16.67%)
Blood and lymphatic system disorders
Anaemia † 1	3/57 (5.26%)	2/45 (4.44%)	0/6 (0.00%)
Febrile neutropenia † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Cardiac disorders
Acute coronary syndrome † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Cardio-respiratory arrest † 1	1/57 (1.75%)	1/45 (2.22%)	0/6 (0.00%)
Endocrine disorders
Hypopituitarism † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Hypothyroidism † 1	2/57 (3.51%)	0/45 (0.00%)	0/6 (0.00%)
Endocrine disorder † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	1/57 (1.75%)	4/45 (8.89%)	0/6 (0.00%)
Dysphagia † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Intestinal obstruction † 1	1/57 (1.75%)	1/45 (2.22%)	0/6 (0.00%)
Large intestinal obstruction † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Obstruction gastric † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Colitis ischaemic † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Dyspepsia † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Vomiting † 1	2/57 (3.51%)	0/45 (0.00%)	0/6 (0.00%)
Colitis † 1	3/57 (5.26%)	0/45 (0.00%)	0/6 (0.00%)
Diarrhoea † 1	7/57 (12.28%)	0/45 (0.00%)	0/6 (0.00%)
Gastrointestinal haemorrhage † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
General disorders
Pyrexia † 1	1/57 (1.75%)	0/45 (0.00%)	1/6 (16.67%)
Hypothermia † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Performance status decreased † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Death † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Disease progression † 1	6/57 (10.53%)	4/45 (8.89%)	0/6 (0.00%)
General physical health deterioration † 1	1/57 (1.75%)	1/45 (2.22%)	0/6 (0.00%)
Malaise † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Asthenia † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Chest pain † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Fatigue † 1	3/57 (5.26%)	1/45 (2.22%)	0/6 (0.00%)
Hepatobiliary disorders
Cholecystocholangitis † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Hyperbilirubinaemia † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Hepatitis acute † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Infections and infestations
Pneumocystis jirovecii pneumonia † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Peritonitis † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Urinary tract infection † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Device related infection † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Escherichia sepsis † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Pneumonia † 1	4/57 (7.02%)	1/45 (2.22%)	0/6 (0.00%)
Abdominal infection † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Injury, poisoning and procedural complications
Compression fracture † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Investigations
Transaminases increased † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Metabolism and nutrition disorders
Decreased appetite † 1	7/57 (12.28%)	0/45 (0.00%)	0/6 (0.00%)
Hypoglycaemia † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Dehydration † 1	2/57 (3.51%)	0/45 (0.00%)	0/6 (0.00%)
Hypokalaemia † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Failure to thrive † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Hyponatraemia † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Hyperglycaemia † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Musculoskeletal and connective tissue disorders
Myalgia † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Back pain † 1	2/57 (3.51%)	0/45 (0.00%)	0/6 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Metastatic gastric cancer † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Malignant neoplasm progression † 1	0/57 (0.00%)	2/45 (4.44%)	0/6 (0.00%)
Gastrointestinal cancer metastatic † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Neoplasm malignant † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Nervous system disorders
Dizziness † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Peripheral sensory neuropathy † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Syncope † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Cerebrovascular accident † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Psychiatric disorders
Delirium † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Renal and urinary disorders
Acute kidney injury † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Haematuria † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	0/57 (0.00%)	1/45 (2.22%)	0/6 (0.00%)
Pneumonia aspiration † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
Pleural effusion † 1	0/57 (0.00%)	2/45 (4.44%)	0/6 (0.00%)
Vascular disorders
Deep vein thrombosis † 1	1/57 (1.75%)	0/45 (0.00%)	0/6 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Ipilimumab	Active Best Supportive Care (BSC)	Non-Active BSC
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	55/57 (96.49%)	42/45 (93.33%)	4/6 (66.67%)
Blood and lymphatic system disorders
Neutropenia † 1	2/57 (3.51%)	7/45 (15.56%)	0/6 (0.00%)
Anaemia † 1	12/57 (21.05%)	5/45 (11.11%)	0/6 (0.00%)
Endocrine disorders
Hypothyroidism † 1	4/57 (7.02%)	0/45 (0.00%)	0/6 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	12/57 (21.05%)	16/45 (35.56%)	0/6 (0.00%)
Dysphagia † 1	0/57 (0.00%)	1/45 (2.22%)	2/6 (33.33%)
Abdominal pain upper † 1	6/57 (10.53%)	4/45 (8.89%)	0/6 (0.00%)
Constipation † 1	10/57 (17.54%)	12/45 (26.67%)	0/6 (0.00%)
Dyspepsia † 1	5/57 (8.77%)	3/45 (6.67%)	0/6 (0.00%)
Gastrooesophageal reflux disease † 1	3/57 (5.26%)	0/45 (0.00%)	0/6 (0.00%)
Nausea † 1	19/57 (33.33%)	16/45 (35.56%)	0/6 (0.00%)
Vomiting † 1	17/57 (29.82%)	12/45 (26.67%)	0/6 (0.00%)
Abdominal distension † 1	3/57 (5.26%)	2/45 (4.44%)	0/6 (0.00%)
Diarrhoea † 1	19/57 (33.33%)	9/45 (20.00%)	0/6 (0.00%)
General disorders
Pyrexia † 1	9/57 (15.79%)	7/45 (15.56%)	0/6 (0.00%)
Pain † 1	3/57 (5.26%)	0/45 (0.00%)	0/6 (0.00%)
Influenza like illness † 1	0/57 (0.00%)	3/45 (6.67%)	0/6 (0.00%)
Asthenia † 1	12/57 (21.05%)	7/45 (15.56%)	0/6 (0.00%)
Chest pain † 1	3/57 (5.26%)	1/45 (2.22%)	0/6 (0.00%)
Chills † 1	3/57 (5.26%)	1/45 (2.22%)	0/6 (0.00%)
Oedema peripheral † 1	8/57 (14.04%)	5/45 (11.11%)	0/6 (0.00%)
Fatigue † 1	26/57 (45.61%)	9/45 (20.00%)	0/6 (0.00%)
Mucosal inflammation † 1	0/57 (0.00%)	4/45 (8.89%)	0/6 (0.00%)
Injury, poisoning and procedural complications
Laceration † 1	1/57 (1.75%)	0/45 (0.00%)	1/6 (16.67%)
Investigations
Alanine aminotransferase increased † 1	9/57 (15.79%)	1/45 (2.22%)	0/6 (0.00%)
Aspartate aminotransferase increased † 1	9/57 (15.79%)	2/45 (4.44%)	0/6 (0.00%)
Weight decreased † 1	11/57 (19.30%)	5/45 (11.11%)	0/6 (0.00%)
Haemoglobin decreased † 1	3/57 (5.26%)	1/45 (2.22%)	0/6 (0.00%)
Weight increased † 1	3/57 (5.26%)	1/45 (2.22%)	1/6 (16.67%)
Metabolism and nutrition disorders
Decreased appetite † 1	21/57 (36.84%)	14/45 (31.11%)	0/6 (0.00%)
Hypokalaemia † 1	8/57 (14.04%)	2/45 (4.44%)	0/6 (0.00%)
Hyponatraemia † 1	3/57 (5.26%)	1/45 (2.22%)	0/6 (0.00%)
Hypoalbuminaemia † 1	5/57 (8.77%)	5/45 (11.11%)	0/6 (0.00%)
Musculoskeletal and connective tissue disorders
Myalgia † 1	4/57 (7.02%)	1/45 (2.22%)	0/6 (0.00%)
Arthralgia † 1	3/57 (5.26%)	4/45 (8.89%)	0/6 (0.00%)
Back pain † 1	6/57 (10.53%)	3/45 (6.67%)	0/6 (0.00%)
Bone pain † 1	0/57 (0.00%)	0/45 (0.00%)	1/6 (16.67%)
Pain in extremity † 1	2/57 (3.51%)	2/45 (4.44%)	1/6 (16.67%)
Neck pain † 1	2/57 (3.51%)	0/45 (0.00%)	1/6 (16.67%)
Nervous system disorders
Dizziness † 1	5/57 (8.77%)	2/45 (4.44%)	0/6 (0.00%)
Peripheral sensory neuropathy † 1	6/57 (10.53%)	1/45 (2.22%)	1/6 (16.67%)
Headache † 1	4/57 (7.02%)	1/45 (2.22%)	0/6 (0.00%)
Neuropathy peripheral † 1	10/57 (17.54%)	7/45 (15.56%)	0/6 (0.00%)
Psychiatric disorders
Anxiety † 1	0/57 (0.00%)	4/45 (8.89%)	0/6 (0.00%)
Insomnia † 1	5/57 (8.77%)	6/45 (13.33%)	0/6 (0.00%)
Respiratory, thoracic and mediastinal disorders
Hiccups † 1	1/57 (1.75%)	4/45 (8.89%)	0/6 (0.00%)
Productive cough † 1	3/57 (5.26%)	2/45 (4.44%)	0/6 (0.00%)
Dyspnoea † 1	6/57 (10.53%)	5/45 (11.11%)	0/6 (0.00%)
Upper respiratory tract inflammation † 1	0/57 (0.00%)	0/45 (0.00%)	1/6 (16.67%)
Cough † 1	5/57 (8.77%)	6/45 (13.33%)	0/6 (0.00%)
Skin and subcutaneous tissue disorders
Skin ulcer † 1	0/57 (0.00%)	0/45 (0.00%)	1/6 (16.67%)
Palmar-plantar erythrodysaesthesia syndrome † 1	4/57 (7.02%)	8/45 (17.78%)	0/6 (0.00%)
Pruritus † 1	25/57 (43.86%)	3/45 (6.67%)	0/6 (0.00%)
Rash † 1	15/57 (26.32%)	2/45 (4.44%)	1/6 (16.67%)
Dry skin † 1	3/57 (5.26%)	2/45 (4.44%)	0/6 (0.00%)
Alopecia † 1	3/57 (5.26%)	2/45 (4.44%)	0/6 (0.00%)
Vascular disorders
Hypertension † 1	2/57 (3.51%)	2/45 (4.44%)	1/6 (16.67%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

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

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

Results Point of Contact

• Name/Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb
• EMail: Clinical.Trials@bms.com

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01585987
• Other Study ID Numbers: CA184-162; 2011-000853-22 ( EudraCT Number )
• First Submitted: April 25, 2012
• First Posted: April 26, 2012
• Results First Submitted: July 15, 2015
• Results First Posted: November 18, 2015
• Last Update Posted: May 17, 2016