Phase 2 Study of Ipilimumab in Children and Adolescents (12 to < 18 Years) With Previously Treated or Untreated, Unresectable Stage III or Stage lV Malignant Melanoma

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01696045
• Collaborator: (none)
• Enrollment: 14
• Locations: 32
• Arms: 2
• Actual Duration (Months): 44.6
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of the study is to comply with the Pediatric Investigation Plan requirements of Ipilimumab

Condition or Disease	Intervention/Treatment	Phase
Malignant Melanoma	Biological: Ipilimumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of Ipilimumab in Children and Adolescents (12 to < 18 Years) With Previously Treated or Untreated, Unresectable Stage III or Stage IV Malignant Melanoma
• Actual Study Start Date: Nov 12, 2012
• Actual Primary Completion Date: Jul 31, 2016
• Actual Study Completion Date: Jul 31, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ipilimumab 3 mg/kg Ipilimumab (3 mg/kg) was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.	Biological: Ipilimumab; Other Names: Yervoy BMS- 734016
Experimental: Ipilimumab 10 mg/kg Ipilimumab (10 mg/kg) was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.	Biological: Ipilimumab; Other Names: Yervoy BMS- 734016

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) Rate at 1 Year [1 year following start of treatment (Assessed up to June 2016, approximately 38 months)]

   Overall Survival (OS) was defined as the time from the start of ipilimumab treatment date to death due to any cause. If a participant had not died, the participant was censored at the time of last contact (last known alive date). OS rates at 1 year were calculated from both Kaplan-Meier estimates and the proportion of participants alive at 1 year following start of treatment.

2. Percentage of Participants With Severe Immune-Mediated Adverse Reactions (imARs) [From first dose to 90 days after last dose (Assessed up to June 2016, approximately 38 months)]

   The percentage of participants with severe Immune-mediated Adverse Reactions (imARs) was determined by dividing the number of participants with grade 3 or worse imARs by the total number of treated participants and expressing this number as a percentage. imARs were AEs determined by the investigator to have an immune-mediated etiology, including inflammatory events associated with ipilimumab treatment.

Secondary Outcome Measures

1. Disease Control Rate (DCR) [From Day 1 of first subject, first treatment to Day 365 of last subject, first treatment (approximately 36 months)]

   Disease control rate was defined as the percentage of all treated participants with a best overall response of Complete Response (CR), Partial Response (PR), or Stable disease (SD), based on the investigator's assessment per mWHO Criteria. CR= Complete disappearance of all non-index lesions. PR= Decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index lesions. SD= Does not meet criteria for complete or partial response, in the absence of progressive disease. PD= At least 25% increase in the sum of the products of all index lesions (taking as reference the smallest sum recorded at or following baseline) and/or the appearance of any new lesion(s).

2. Progression Free Survival [From date of first treatment until disease progression or death (Assessed up to June 2016, approximately 38 months)]

   Progression-Free Survival was defined as the time from the start of ipilimumab treatment to disease progression or death, whichever occurs first. A participant who died without reported progression was considered to have progressed on their date of death. For participants who remained alive and had not progressed, PFS was censored on the date of the last tumor assessment.

3. Best Overall Response Rate (BORR) [From Day 1 of first subject, first treatment to Day 365 of last subject, first treatment (approximately 36 months)]

   Best Overall Response Rate (BORR) was defined as the total number of participants with the best overall response of Complete Response (CR) or Partial Response (PR) divided by the total number of treated participants and expressed as a percentage. CR= Complete disappearance of all non-index lesions. PR= Decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index lesions. SD= Does not meet criteria for complete or partial response, in the absence of progressive disease. PD= At least 25% increase in the sum of the products of all index lesions (taking as reference the smallest sum recorded at or following baseline) and/or the appearance of any new lesion(s).

4. Overall Survival Time [From date of first treatment to date of death (Assessed up to June 2016, approximately 38 months)]

   Overall Survival time was defined as the time from the start of ipilimumab treatment date to date of death due to any cause. Participants who had not died were censored at the time of last contact (last known alive date).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

• 12 < 18 years of age

• Previously treated or untreated, unresectable Stage III or Stage IV malignant melanoma

• Karnofsky Performance Status (KPS) or Lansky Score ≥ 50

Exclusion Criteria:

• Primary Ocular Melanoma

• Prior therapy with a Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) or Programmed death- 1 (PD-1) antagonist, or Programmed cell death- ligand 1 (PD-L1) or CD137 agonists

• Symptomatic brain metastases

• History of autoimmune diseases

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children'S Hospital	Phoenix	Arizona	United States	85016
2	Childrens Hospital Of La	Los Angeles	California	United States	90027
3	Children'S Hospital Of Orange County	Orange	California	United States	92868
4	Children'S Hospital Colorado	Aurora	Colorado	United States	80045
5	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida	United States	33612
6	James Whitcomb Riley Hospital For Children	Indianapolis	Indiana	United States	46202
7	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
8	Mayo Clinic	Rochester	Minnesota	United States	55905
9	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
10	University Of Pittsburgh Medical Center Cancer Center	Pittsburgh	Pennsylvania	United States	15232
11	St. Jude Children'S Research Hospital	Memphis	Tennessee	United States	38105
12	The University Of Texas Md Anderson Cancer Center	Houston	Texas	United States	77030
13	Primary Children'S Medical Center	Salt Lake City	Utah	United States	84113
14	University Of Utah	Salt Lake City	Utah	United States	84113
15	Local Institution	Gent		Belgium	9000
16	Local Institution	Copenhagen		Denmark	2100
17	Local Institution	Lyon		France	69008
18	Local Institution	Marseille Cedex 5		France	13385
19	Local Institution	Nantes Cedex 1		France	44093
20	Local Institution	Villejuif Cedex		France	94805
21	Local Institution	Dortmund		Germany	44137
22	Local Institution	Erlangen		Germany	91054
23	Local Institution	Hamburg		Germany	20246
24	Local Institution	M?nster		Germany	48149
25	Local Institution	Munster		Germany	48149
26	Local Institution	Mexico	D.F	Mexico	02990
27	Local Institution	Df	Distrito Federal	Mexico	06720
28	Local Institution	Leon, Guanajato	Guanajuato	Mexico	37000
29	Local Institution	Esplugues de Llobregat- Barcelona		Spain	08950
30	Local Institution	Bristol	Avon	United Kingdom	BS2 8BJ
31	Local Institution	Newcastle	Northumberland	United Kingdom	NE1 4LP
32	Local Institution	Sutton	Surrey	United Kingdom	SM2 5PT

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BMS Clinical Trial Patient Recruiting

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01696045
• Other Study ID Numbers: CA184-178; 2012-002249-39
• First Posted: Sep 28, 2012
• Last Update Posted: Aug 29, 2017
• Last Verified: Jul 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Melanoma; Ipilimumab

Study Results

Participant Flow

Pre-assignment Detail	14 participants were enrolled in the study. 12 participants received study treatment. 2 participants were enrolled and not treated because they no longer met study criteria.

Arm/Group Title	Ipilimumab 3mg/kg	Ipilimumab 10mg/kg
Arm/Group Description	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.
Period Title: Overall Study
STARTED	4	8
COMPLETED	1	1
NOT COMPLETED	3	7

Baseline Characteristics

Arm/Group Title	Ipilimumab 3mg/kg	Ipilimumab 10mg/kg	Total
Arm/Group Description	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.	Total of all reporting groups
Overall Participants	4	8	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.3 (1.89)	14.9 (0.64)	14.3 (1.37)
Sex: Female, Male (Count of Participants)
Female	2 50%	3 37.5%	5 41.7%
Male	2 50%	5 62.5%	7 58.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 25%	0 0%	1 8.3%
White	3 75%	8 100%	11 91.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS) Rate at 1 Year
Description	Overall Survival (OS) was defined as the time from the start of ipilimumab treatment date to death due to any cause. If a participant had not died, the participant was censored at the time of last contact (last known alive date). OS rates at 1 year were calculated from both Kaplan-Meier estimates and the proportion of participants alive at 1 year following start of treatment.
Time Frame	1 year following start of treatment (Assessed up to June 2016, approximately 38 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Ipilimumab 3mg/kg	Ipilimumab 10mg/kg
Arm/Group Description	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.
Measure Participants	4	8
OS Rate (Kaplan-Meier estimates)	75.0 1875%	62.5 781.3%
OS Rate (Proportion of surviving participants)	75.0 1875%	62.5 781.3%

2. Primary Outcome

Title	Percentage of Participants With Severe Immune-Mediated Adverse Reactions (imARs)
Description	The percentage of participants with severe Immune-mediated Adverse Reactions (imARs) was determined by dividing the number of participants with grade 3 or worse imARs by the total number of treated participants and expressing this number as a percentage. imARs were AEs determined by the investigator to have an immune-mediated etiology, including inflammatory events associated with ipilimumab treatment.
Time Frame	From first dose to 90 days after last dose (Assessed up to June 2016, approximately 38 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Ipilimumab 3mg/kg	Ipilimumab 10mg/kg
Arm/Group Description	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.
Measure Participants	4	8
Number (95% Confidence Interval) [percentage of participants]	25.0 625%	62.5 781.3%

3. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	Disease control rate was defined as the percentage of all treated participants with a best overall response of Complete Response (CR), Partial Response (PR), or Stable disease (SD), based on the investigator's assessment per mWHO Criteria. CR= Complete disappearance of all non-index lesions. PR= Decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index lesions. SD= Does not meet criteria for complete or partial response, in the absence of progressive disease. PD= At least 25% increase in the sum of the products of all index lesions (taking as reference the smallest sum recorded at or following baseline) and/or the appearance of any new lesion(s).
Time Frame	From Day 1 of first subject, first treatment to Day 365 of last subject, first treatment (approximately 36 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Ipilimumab 3mg/kg	Ipilimumab 10mg/kg
Arm/Group Description	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.
Measure Participants	4	8
Number (95% Confidence Interval) [Percentage of participants]	25.0 625%	37.5 468.8%

4. Secondary Outcome

Title	Progression Free Survival
Description	Progression-Free Survival was defined as the time from the start of ipilimumab treatment to disease progression or death, whichever occurs first. A participant who died without reported progression was considered to have progressed on their date of death. For participants who remained alive and had not progressed, PFS was censored on the date of the last tumor assessment.
Time Frame	From date of first treatment until disease progression or death (Assessed up to June 2016, approximately 38 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Ipilimumab 3mg/kg	Ipilimumab 10mg/kg
Arm/Group Description	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.
Measure Participants	4	8
Median (95% Confidence Interval) [months]	2.6	2.9

5. Secondary Outcome

Title	Best Overall Response Rate (BORR)
Description	Best Overall Response Rate (BORR) was defined as the total number of participants with the best overall response of Complete Response (CR) or Partial Response (PR) divided by the total number of treated participants and expressed as a percentage. CR= Complete disappearance of all non-index lesions. PR= Decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index lesions. SD= Does not meet criteria for complete or partial response, in the absence of progressive disease. PD= At least 25% increase in the sum of the products of all index lesions (taking as reference the smallest sum recorded at or following baseline) and/or the appearance of any new lesion(s).
Time Frame	From Day 1 of first subject, first treatment to Day 365 of last subject, first treatment (approximately 36 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Ipilimumab 3mg/kg	Ipilimumab 10mg/kg
Arm/Group Description	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.
Measure Participants	4	8
Number (95% Confidence Interval) [percentage of participants]	0.0 0%	25.0 312.5%

6. Secondary Outcome

Title	Overall Survival Time
Description	Overall Survival time was defined as the time from the start of ipilimumab treatment date to date of death due to any cause. Participants who had not died were censored at the time of last contact (last known alive date).
Time Frame	From date of first treatment to date of death (Assessed up to June 2016, approximately 38 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Ipilimumab 3mg/kg	Ipilimumab 10mg/kg
Arm/Group Description	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.
Measure Participants	4	8
Median (95% Confidence Interval) [months]	18.2	NA

Adverse Events

Time Frame	From date of first dose to 90 days after date of last dose, assessed up to study completion (approximately 38 months)
Arm/Group Title	IPILIMUMAB 3 MG/KG		IPILIMUMAB 10 MG/KG
Arm/Group Description	Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.		Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.
All Cause Mortality
	IPILIMUMAB 3 MG/KG		IPILIMUMAB 10 MG/KG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IPILIMUMAB 3 MG/KG		IPILIMUMAB 10 MG/KG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		6/8 (75%)
Gastrointestinal disorders
Pancreatitis	0/4 (0%)		1/8 (12.5%)
Hepatobiliary disorders
Cholecystitis acute	0/4 (0%)		1/8 (12.5%)
Cholestasis	0/4 (0%)		1/8 (12.5%)
Hepatitis	1/4 (25%)		1/8 (12.5%)
Injury, poisoning and procedural complications
Infusion related reaction	0/4 (0%)		1/8 (12.5%)
Investigations
Hepatic enzyme increased	0/4 (0%)		1/8 (12.5%)
Transaminases increased	0/4 (0%)		1/8 (12.5%)
Metabolism and nutrition disorders
Hypokalaemia	0/4 (0%)		1/8 (12.5%)
Hyponatraemia	0/4 (0%)		1/8 (12.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic malignant melanoma	0/4 (0%)		1/8 (12.5%)
Tumour pain	0/4 (0%)		1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/4 (0%)		2/8 (25%)
Other (Not Including Serious) Adverse Events
	IPILIMUMAB 3 MG/KG		IPILIMUMAB 10 MG/KG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		8/8 (100%)
Blood and lymphatic system disorders
Anaemia	0/4 (0%)		1/8 (12.5%)
Cardiac disorders
Tachycardia	0/4 (0%)		1/8 (12.5%)
Ventricular extrasystoles	0/4 (0%)		1/8 (12.5%)
Ventricular tachycardia	0/4 (0%)		1/8 (12.5%)
Eye disorders
Eyelid pain	0/4 (0%)		1/8 (12.5%)
Photophobia	0/4 (0%)		1/8 (12.5%)
Vision blurred	0/4 (0%)		1/8 (12.5%)
Gastrointestinal disorders
Abdominal pain	1/4 (25%)		2/8 (25%)
Ascites	0/4 (0%)		1/8 (12.5%)
Constipation	0/4 (0%)		3/8 (37.5%)
Diarrhoea	0/4 (0%)		4/8 (50%)
Haematochezia	0/4 (0%)		1/8 (12.5%)
Nausea	1/4 (25%)		6/8 (75%)
Pancreatitis	0/4 (0%)		1/8 (12.5%)
Vomiting	1/4 (25%)		7/8 (87.5%)
General disorders
Asthenia	1/4 (25%)		0/8 (0%)
Axillary pain	0/4 (0%)		1/8 (12.5%)
Chest pain	0/4 (0%)		1/8 (12.5%)
Chills	0/4 (0%)		1/8 (12.5%)
Fatigue	0/4 (0%)		4/8 (50%)
Pain	0/4 (0%)		1/8 (12.5%)
Pyrexia	1/4 (25%)		3/8 (37.5%)
Hepatobiliary disorders
Hepatitis	1/4 (25%)		0/8 (0%)
Immune system disorders
Drug hypersensitivity	1/4 (25%)		0/8 (0%)
Hypersensitivity	1/4 (25%)		0/8 (0%)
Infections and infestations
Candida nappy rash	0/4 (0%)		1/8 (12.5%)
Conjunctivitis	1/4 (25%)		0/8 (0%)
Infection	0/4 (0%)		1/8 (12.5%)
Rhinitis	0/4 (0%)		1/8 (12.5%)
Rotavirus infection	0/4 (0%)		1/8 (12.5%)
Tonsillitis	0/4 (0%)		1/8 (12.5%)
Upper respiratory tract infection	0/4 (0%)		1/8 (12.5%)
Urinary tract infection	0/4 (0%)		1/8 (12.5%)
Injury, poisoning and procedural complications
Contusion	0/4 (0%)		1/8 (12.5%)
Infusion related reaction	0/4 (0%)		1/8 (12.5%)
Investigations
Alanine aminotransferase increased	0/4 (0%)		2/8 (25%)
Amylase increased	0/4 (0%)		1/8 (12.5%)
Aspartate aminotransferase increased	0/4 (0%)		2/8 (25%)
Blood albumin decreased	0/4 (0%)		1/8 (12.5%)
Blood bilirubin increased	0/4 (0%)		1/8 (12.5%)
Blood calcium decreased	0/4 (0%)		1/8 (12.5%)
Blood glucose increased	0/4 (0%)		1/8 (12.5%)
Blood magnesium decreased	0/4 (0%)		1/8 (12.5%)
Blood phosphorus decreased	0/4 (0%)		1/8 (12.5%)
Blood potassium decreased	0/4 (0%)		1/8 (12.5%)
Blood sodium decreased	0/4 (0%)		1/8 (12.5%)
Coagulation factor increased	0/4 (0%)		1/8 (12.5%)
Lipase increased	0/4 (0%)		1/8 (12.5%)
Platelet count decreased	0/4 (0%)		1/8 (12.5%)
Weight decreased	0/4 (0%)		4/8 (50%)
White blood cell count increased	0/4 (0%)		1/8 (12.5%)
Metabolism and nutrition disorders
Decreased appetite	0/4 (0%)		4/8 (50%)
Dehydration	0/4 (0%)		2/8 (25%)
Hyperglycaemia	0/4 (0%)		2/8 (25%)
Hyperkalaemia	0/4 (0%)		1/8 (12.5%)
Hypernatraemia	0/4 (0%)		1/8 (12.5%)
Hyperuricaemia	0/4 (0%)		1/8 (12.5%)
Hypoalbuminaemia	0/4 (0%)		1/8 (12.5%)
Hypocalcaemia	0/4 (0%)		1/8 (12.5%)
Hypokalaemia	0/4 (0%)		2/8 (25%)
Hyponatraemia	0/4 (0%)		3/8 (37.5%)
Musculoskeletal and connective tissue disorders
Back pain	0/4 (0%)		1/8 (12.5%)
Muscle fatigue	0/4 (0%)		1/8 (12.5%)
Muscle spasms	0/4 (0%)		1/8 (12.5%)
Myalgia	0/4 (0%)		2/8 (25%)
Pain in jaw	0/4 (0%)		1/8 (12.5%)
Nervous system disorders
Dizziness	0/4 (0%)		1/8 (12.5%)
Dysgeusia	0/4 (0%)		1/8 (12.5%)
Headache	2/4 (50%)		5/8 (62.5%)
Tremor	0/4 (0%)		1/8 (12.5%)
Psychiatric disorders
Mood altered	0/4 (0%)		1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Cough	1/4 (25%)		2/8 (25%)
Dyspnoea	0/4 (0%)		1/8 (12.5%)
Epistaxis	0/4 (0%)		2/8 (25%)
Hypoxia	0/4 (0%)		1/8 (12.5%)
Laryngeal pain	0/4 (0%)		1/8 (12.5%)
Nasal congestion	1/4 (25%)		0/8 (0%)
Pleural effusion	0/4 (0%)		2/8 (25%)
Pneumothorax	0/4 (0%)		1/8 (12.5%)
Skin and subcutaneous tissue disorders
Acne	0/4 (0%)		1/8 (12.5%)
Dry skin	0/4 (0%)		1/8 (12.5%)
Hyperhidrosis	0/4 (0%)		2/8 (25%)
Pain of skin	0/4 (0%)		1/8 (12.5%)
Pruritus	1/4 (25%)		2/8 (25%)
Rash	1/4 (25%)		3/8 (37.5%)
Skin disorder	0/4 (0%)		1/8 (12.5%)
Vascular disorders
Hot flush	0/4 (0%)		1/8 (12.5%)
Hypertension	0/4 (0%)		1/8 (12.5%)
Hypotension	0/4 (0%)		1/8 (12.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.