CheckMate331: Effectiveness Study of Nivolumab Compared to Chemotherapy in Patients With Relapsed Small-cell Lung Cancer

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02481830
• Collaborator: Ono Pharmaceutical Co. Ltd (Industry)
• Enrollment: 803
• Locations: 150
• Arms: 3
• Anticipated Duration (Months): 80.5
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the overall survival of nivolumab versus chemotherapy in subjects with relapsed SCLC.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: Nivolumab; Drug: Topotecan; Drug: Amrubicin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 803 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Randomized, Phase 3 Study of Nivolumab or Chemotherapy in Subjects With Relapsed Small-cell Lung Cancer After Platinum-based First Line Chemotherapy (CheckMate 331: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 331)
• Actual Study Start Date: Sep 14, 2015
• Actual Primary Completion Date: Aug 17, 2018
• Anticipated Study Completion Date: May 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Nivolumab Nivolumab intravenous infusion as specified	Drug: Nivolumab
Active Comparator: Arm B Chemotherapy Topotecan Topotecan as specified	Drug: Topotecan
Active Comparator: Arm B Chemotherapy Amrubicin Amrubicin intravenous infusion as specified (upon investigator's choice, where locally approved for 2nd line SCLC treatment)	Drug: Amrubicin

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [OS was followed continuously while participants were on the study drug and every 3 months ,minimum follow up for overall survival was 15.8 months]

   The time from randomization to the date of death, data was based on Kaplan-Meier Estimates.

Secondary Outcome Measures

1. Progression Free Survival (PFS ) [assessed every 6 weeks from the first dose to week 30, and every 12 weeks up to 34 months.]

   the time from randomization to the date of the first documented tumor progression (based on investigator assesment,using Response Evaluation Criteria in Solid Tumors (RECIST)1.1 criteria) or death the data was based on Kaplan-Meier Estimates. PFS was censored when subsequent anti cancer therapy was started before progression.

2. Objective Response Rate (ORR) [Between the date of randomization and the date of progression or the date of subsequent anti-cancer therapy,whichever occurs first up to 34 months]

   The proportion of all randomized Participants who achieved BOR(Best Overall response) from baseline is either a CR(complete response) or PR(Partial response),using the RECIST v1.1 criteria based on investigator assessment,CR+PR, confidence interval based on the Clopper and Pearson method

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed small cell lung cancer (SCLC)

• Subjects with either limited or extensive disease stage at the initial diagnosis

• Must have recurrence or progression after platinum-based first-line chemotherapy or chemoradiation therapy for the treatment of limited or extensive disease stage SCLC

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

Exclusion Criteria:

• Untreated or symptomatic central nervous system (CNS) metastases

• Prior therapy with anti-PD-1, anti-PDL1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody

• Inadequate hematologic or hepatic function

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ Of Ark For Med Sci	Little Rock	Arkansas	United States	72205
2	Smilow Cancer Hospital. At Yale New Haven	New Haven	Connecticut	United States	06520
3	Emory University	Atlanta	Georgia	United States	30322
4	Washington University School Of Medicine	Saint Louis	Missouri	United States	63110
5	Nebraska Hematology Oncology Pc	Lincoln	Nebraska	United States	68506
6	Broome Oncology	Johnson City	New York	United States	13790
7	Duke University	Durham	North Carolina	United States	27710
8	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
9	St. Luke's University Health Network	Bethlehem	Pennsylvania	United States	18015
10	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17604
11	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111-2412
12	Tennessee Oncology, Pllc	Nashville	Tennessee	United States	37203
13	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
14	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
15	Local Institution	Waratah	New South Wales	Australia	2298
16	Local Institution	Brisbane	Queensland	Australia	4032
17	Local Institution	Elizabeth Vale	South Australia	Australia	5112
18	Local Institution	Kurralta Park	South Australia	Australia	5037
19	Local Institution	Perth	Western Australia	Australia	6150
20	Local Institution	Murdoch		Australia	6150
21	Local Institution	Graz		Austria	8036
22	Local Institution	Wels		Austria	4600
23	Akh Wien	Wien		Austria	1090
24	Local Institution	Bruxelles		Belgium	1200
25	Local Institution	Edegem		Belgium	2650
26	Local Institution	Leuven		Belgium	3000
27	Local Institution	Yvoir		Belgium	5530
28	Local Institution	Ijui	RIO Grande DO SUL	Brazil	98700-000
29	Local Institution	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
30	Local Institution	Barretos	Sao Paulo	Brazil	14784-400
31	Local Institution	Sao Paulo		Brazil	01321-001
32	Local Institution	Recoleta	Santiago De Chile	Chile
33	Local Institution	Beijing	Beijing	China	100001
34	Local Institution	Beijing	Beijing	China	100021
35	Local Institution	Beijing	Beijing	China	100032
36	Local Institution	Beijing	Beijing	China	101149
37	Local Institution	Guanzhou	Guangdong	China	510080
38	Local Institution	Zhengzhou	Henan	China	450008
39	Local Institution	Nanjing	Jiangsu	China	210000
40	Local Institution	Changchun	Jilin	China	130012
41	Local Institution	Xian	Shaanxi	China	710038
42	Local Institution	Shanghai	Shanghai	China	200025
43	Local Institution	Shanghai	Shanghai	China	200032
44	Local Institution	Urumqi	Xinjiang	China	830011
45	Local Institution	Hangzhou	Zhejiang	China	310022
46	Local Institution	Beijing		China	100071
47	Local Institution	Guangzhou		China
48	Local Institution	Hangzhou		China	310016
49	Local Institution	Shanghai		China	200030
50	Local Institution	Brno		Czechia	625 00
51	Klinika komplexni onkologicke pece	Brno		Czechia	656 53
52	Klinika plicnich nemoci a tuberkulozy	Olomouc		Czechia	779 00
53	Pneumologicka klinika 1. LF a TN	Praha 4		Czechia	14059
54	Local Institution	Copenhagen		Denmark	2100
55	Local Institution	Herlev		Denmark	2730
56	Local Institution	Odense		Denmark	5000
57	Chu Brest Hopital Morvan	Brest		France	29200
58	CHRU Lille - Hopital Calmette	Lille Cedex		France	59037
59	Hopital Cochin	Paris Cedex 14		France	75014
60	Centre Hospitalier D'Annecy	Pringy Cedex		France	74374
61	Polyclinique De Courlancy	Reims		France	51100
62	Hopital Sainte Musse	Toulon Cedex		France	83056
63	Local Institution	Bamberg		Germany	96049
64	Local Institution	Berlin		Germany	13125
65	Local Institution	Essen		Germany	45122
66	Local Institution	Frankfurt am Main		Germany	60590
67	Local Institution	Gera		Germany	07548
68	Local Institution	Gerlingen		Germany	70839
69	Local Institution	Grosshansdorf		Germany	22927
70	Local Institution	Halle (saale)		Germany	06120
71	Local Institution	Hamburg		Germany	21075
72	Local Institution	Heidelberg		Germany	69126
73	Local Institution	Immenstadt		Germany	87509
74	Local Institution	Koeln		Germany	50937
75	Local Institution	Muenchen		Germany	81925
76	Local Institution	Oberhausen		Germany	46145
77	Local Institution	Regensburg		Germany	93053
78	University Hospital Of Heraklion	Heraklion	Creta	Greece	71110
79	Sotiria General Hospital	Athens		Greece	11527
80	Papageorgiou General Hospital	Thessaloniki		Greece	56429
81	Pulmonologiai Klinika	Budapest		Hungary	1083
82	Orsz.Koranyi Tbc es Pulm.Int.	Budapest		Hungary	1121
83	Local Institution	Beer Sheva		Israel	84101
84	Local Institution	Kfar Saba		Israel
85	Local Institution	Ramat -Gan		Israel	52621
86	Local Institution	Safed		Israel	13100
87	Ospedale Bellaria-Maggiore	Bologna		Italy	40139
88	Ospedale Civile Di Livorno	Livorno		Italy	57100
89	Ospedale San Luca	Lucca		Italy	55100
90	IRST Meldola	Meldola		Italy	47014
91	Local Institution	Milano		Italy	20133
92	Azienda Ospedaliera - Nuovo Ospedale San Gerardo	Monza		Italy	20052
93	Ospedale Degli Infermi	Rimini		Italy	47923
94	Azienda Ospedaliera S. Andrea	Roma		Italy	00189
95	Local Institution	Nagoya-shi	Aichi	Japan	4648681
96	Local Institution	Nagoya	Aichi	Japan	460-0001
97	Local Institution	Kashiwa	Chiba	Japan	277-8577
98	Local Institution	Matsuyama	Ehime	Japan	7910280
99	Local Institution	Fukuoka-shi	Fukuoka	Japan	811-1395
100	Local Institution	Akashi-shi	Hyogo	Japan	6738558
101	Local Institution	Kobe	Hyogo	Japan	6500047
102	Local Institution	Natori-shi	Miyagi	Japan	9811293
103	Local Institution - 0161	Niigata-shi	Niigata	Japan	951-8566
104	Local Institution	Habikino-shi	Osaka	Japan	5838588
105	Local Institution	Hirakata-shi	Osaka	Japan	5731191
106	Local Institution	Osaka-sayama	Osaka	Japan	589-8511
107	Local Institution	Osaka-shi	Osaka	Japan	5340021
108	Local Institution	Sakai	Osaka	Japan	591-8555
109	Local Institution	Kitaadachi-gun	Saitama	Japan	362-0806
110	Local Institution	Bunkyo-ku	Tokyo	Japan	1138431
111	Local Institution	Chuo-ku	Tokyo	Japan	1040045
112	Local Institution	Chuo-ku	Tokyo	Japan	5418567
113	Local Institution	Wakayama-Shi	Wakayama	Japan	641-8510
114	Local Institution	Tokyo		Japan	135-8550
115	Local Institution	Suwon	Gyeonggi-do	Korea, Republic of	16247
116	Local Institution	Cheongju-si		Korea, Republic of	28644
117	Local Institution	Seoul		Korea, Republic of	02841
118	Local Institution	Seoul		Korea, Republic of	05505
119	Local Institution	Bergen		Norway	5021
120	Local Institution	Oslo		Norway	0424
121	Wojewodzki Szpital Zespolony W Elblagu	Elblag		Poland	82-300
122	Klinika Onkologii I Radioterapii Am	Gdansk		Poland	80-214
123	Oddzial Onkologiczny	Krakow		Poland	31-202
124	Regionalny Osrodek Onkologiczny	Lodz		Poland	93-513
125	Oddzial Onkologii Klinicznej	Poznan		Poland	60-569
126	Klinika Nowotworow Pluca i Klatki Piersiowej	Warszawa		Poland	02-781
127	Local Institution	Bucharest		Romania	020122
128	Local Institution	Craiova		Romania	200347
129	Local Institution	Romania		Romania	400015
130	Local Institution	Timisoara, Timis		Romania	300239
131	Local Institution	Moscow		Russian Federation	115478
132	Local Institution	Ryazan		Russian Federation	390011
133	Local Institution	Saint-Petersburg		Russian Federation	197758
134	Local Institution	St. Petersburg		Russian Federation	194291
135	Local Institution	Barcelona		Spain	08025
136	Local Institution	Barcelona		Spain	08035
137	Local Institution	Madrid		Spain	28034
138	Local Institution	Madrid		Spain	28050
139	Local Institution	Sevilla		Spain	41009
140	Local Institution	Valencia		Spain	46026
141	Local Institution	Basel		Switzerland	4031
142	Centre hospitalier universitaire Vaudois (CHUV)	Lausanne		Switzerland	1011
143	Local Institution	Winterthur		Switzerland	8401
144	Local Institution	Zurich		Switzerland	8091
145	Local Institution	Taichung		Taiwan	404
146	Local Institution	London	Greater London	United Kingdom	SW3 6JJ
147	Local Institution	Manchester	Greater Manchester	United Kingdom	M20 4XB
148	Local Institution	Maidstone	Kent	United Kingdom	ME16 9QQ
149	Local Institution	Sutton	Surrey	United Kingdom	SM2 5PT
150	Local Institution	Southampton		United Kingdom	SO16 6YD

Sponsors and Collaborators

• Bristol-Myers Squibb
• Ono Pharmaceutical Co. Ltd

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Apr 22, 2015
• Statistical Analysis Plan - Aug 14, 2018

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02481830
• Other Study ID Numbers: CA209-331; 2015-001097-18
• First Posted: Jun 25, 2015
• Last Update Posted: Apr 11, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Nivolumab; Topotecan; Amrubicin

Study Results

Participant Flow

Pre-assignment Detail	803 Participants were enrolled into the study,569 Randomized ,212 not randomized, reasons not randomized:2 adverse events(AEs),20 consent withdraw, 12 death, 2 loss of follow up,176 not meet study criteria.

Arm/Group Title	Group A	Group B
Arm/Group Description	Nivolumab 240mg	Chemotherapy (Topotecan/Amrubicin)
Period Title: Overall Study
STARTED	284	285
COMPLETED	282	265
NOT COMPLETED	2	20

Baseline Characteristics

Arm/Group Title	Group A	Group B	Total
Arm/Group Description	Nivolumab 240mg	Chemotherapy (Topotecan/Amrubicin)	Total of all reporting groups
Overall Participants	284	285	569
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.5 (9.2)	61.6 (8.4)	61.6 (8.8)
Sex: Female, Male (Count of Participants)
Female	110 38.7%	108 37.9%	218 38.3%
Male	174 61.3%	177 62.1%	351 61.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 1.4%	6 2.1%	10 1.8%
Not Hispanic or Latino	125 44%	142 49.8%	267 46.9%
Unknown or Not Reported	155 54.6%	137 48.1%	292 51.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.4%	1 0.2%
Asian	70 24.6%	71 24.9%	141 24.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 0.4%	2 0.7%	3 0.5%
White	211 74.3%	211 74%	422 74.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 0.7%	0 0%	2 0.4%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	The time from randomization to the date of death, data was based on Kaplan-Meier Estimates.
Time Frame	OS was followed continuously while participants were on the study drug and every 3 months ,minimum follow up for overall survival was 15.8 months

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Group A	Group B
Arm/Group Description	Nivolumab 240mg	Chemotherapy (Topotecan/Amrubicin)
Measure Participants	284	285
Median (95% Confidence Interval) [Months]	7.46	8.38

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A, Group B
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1144
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratified Cox proportional hazard model. Hazard Ratio is Nivolumab over Topotecan/Amrubicin

2. Secondary Outcome

Title	Progression Free Survival (PFS )
Description	the time from randomization to the date of the first documented tumor progression (based on investigator assesment,using Response Evaluation Criteria in Solid Tumors (RECIST)1.1 criteria) or death the data was based on Kaplan-Meier Estimates. PFS was censored when subsequent anti cancer therapy was started before progression.
Time Frame	assessed every 6 weeks from the first dose to week 30, and every 12 weeks up to 34 months.

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Group A	Group B
Arm/Group Description	Nivolumab 240mg	Chemotherapy (Topotecan/Amrubicin)
Measure Participants	284	285
Median (95% Confidence Interval) [Months]	1.45	3.78

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A, Group B
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.41
	Confidence Interval	(2-Sided) 95%; 1.18 to 1.69
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratified Cox proportional hazard model. Hazard Ratio is Nivolumab over Topotecan/Amrubicin

3. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	The proportion of all randomized Participants who achieved BOR(Best Overall response) from baseline is either a CR(complete response) or PR(Partial response),using the RECIST v1.1 criteria based on investigator assessment,CR+PR, confidence interval based on the Clopper and Pearson method
Time Frame	Between the date of randomization and the date of progression or the date of subsequent anti-cancer therapy,whichever occurs first up to 34 months

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Group A	Group B
Arm/Group Description	Nivolumab 240mg	Chemotherapy (Topotecan/Amrubicin)
Measure Participants	284	285
Number (95% Confidence Interval) [Percentage of Participants]	13.7 4.8%	16.5 5.8%

Adverse Events

Time Frame	Reporting Adverse Events (AEs) include events reported between first dose and 30 days after last dose of study therapy.
Adverse Event Reporting Description	If a participant experienced more than 1 of a given AE, the participant is counted only once for that AE.
Arm/Group Title	Group A		Group B
Arm/Group Description	Nivolumab 240mg		Chemotherapy (Topotecan/Amrubicin)
All Cause Mortality
	Group A		Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	223/282 (79.1%)		235/265 (88.7%)
Serious Adverse Events
	Group A		Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	143/282 (50.7%)		138/265 (52.1%)
Blood and lymphatic system disorders
Anaemia	1/282 (0.4%)		15/265 (5.7%)
Bone marrow failure	0/282 (0%)		11/265 (4.2%)
Febrile neutropenia	1/282 (0.4%)		23/265 (8.7%)
Leukopenia	0/282 (0%)		2/265 (0.8%)
Lymphadenopathy	0/282 (0%)		1/265 (0.4%)
Neutropenia	0/282 (0%)		11/265 (4.2%)
Pancytopenia	0/282 (0%)		7/265 (2.6%)
Thrombocytopenia	1/282 (0.4%)		15/265 (5.7%)
Cardiac disorders
Acute myocardial infarction	0/282 (0%)		1/265 (0.4%)
Atrial fibrillation	1/282 (0.4%)		0/265 (0%)
Atrial flutter	0/282 (0%)		1/265 (0.4%)
Cardiac failure	2/282 (0.7%)		1/265 (0.4%)
Cardiac failure acute	1/282 (0.4%)		0/265 (0%)
Cardiac tamponade	1/282 (0.4%)		0/265 (0%)
Cardio-respiratory arrest	0/282 (0%)		1/265 (0.4%)
Pericardial effusion	1/282 (0.4%)		0/265 (0%)
Endocrine disorders
Adrenocorticotropic hormone deficiency	1/282 (0.4%)		0/265 (0%)
Cushing's syndrome	1/282 (0.4%)		0/265 (0%)
Hyperthyroidism	2/282 (0.7%)		0/265 (0%)
Inappropriate antidiuretic hormone secretion	0/282 (0%)		1/265 (0.4%)
Secondary adrenocortical insufficiency	0/282 (0%)		1/265 (0.4%)
Gastrointestinal disorders
Abdominal hernia obstructive	1/282 (0.4%)		0/265 (0%)
Abdominal pain	3/282 (1.1%)		2/265 (0.8%)
Abdominal pain upper	0/282 (0%)		1/265 (0.4%)
Ascites	1/282 (0.4%)		0/265 (0%)
Autoimmune colitis	1/282 (0.4%)		0/265 (0%)
Colitis	2/282 (0.7%)		0/265 (0%)
Diarrhoea	2/282 (0.7%)		1/265 (0.4%)
Dysphagia	1/282 (0.4%)		0/265 (0%)
Gastric haemorrhage	1/282 (0.4%)		0/265 (0%)
Gastrooesophageal reflux disease	1/282 (0.4%)		0/265 (0%)
Intestinal haemorrhage	0/282 (0%)		1/265 (0.4%)
Intestinal obstruction	1/282 (0.4%)		0/265 (0%)
Nausea	1/282 (0.4%)		1/265 (0.4%)
Oral disorder	1/282 (0.4%)		0/265 (0%)
Vomiting	2/282 (0.7%)		1/265 (0.4%)
General disorders
Asthenia	0/282 (0%)		3/265 (1.1%)
Chest pain	1/282 (0.4%)		0/265 (0%)
Disease progression	1/282 (0.4%)		1/265 (0.4%)
Fatigue	0/282 (0%)		1/265 (0.4%)
General physical health deterioration	8/282 (2.8%)		3/265 (1.1%)
Non-cardiac chest pain	1/282 (0.4%)		1/265 (0.4%)
Oedema	1/282 (0.4%)		0/265 (0%)
Pain	1/282 (0.4%)		2/265 (0.8%)
Pyrexia	3/282 (1.1%)		3/265 (1.1%)
Sudden death	0/282 (0%)		1/265 (0.4%)
Hepatobiliary disorders
Hepatic failure	1/282 (0.4%)		0/265 (0%)
Hepatitis	1/282 (0.4%)		0/265 (0%)
Jaundice cholestatic	1/282 (0.4%)		0/265 (0%)
Infections and infestations
Appendicitis	1/282 (0.4%)		0/265 (0%)
Bacteraemia	0/282 (0%)		1/265 (0.4%)
Bronchitis	1/282 (0.4%)		0/265 (0%)
Cellulitis	0/282 (0%)		1/265 (0.4%)
Device related infection	0/282 (0%)		2/265 (0.8%)
Encephalitis	1/282 (0.4%)		0/265 (0%)
Enterocolitis infectious	0/282 (0%)		1/265 (0.4%)
Erysipelas	0/282 (0%)		1/265 (0.4%)
Herpes simplex	1/282 (0.4%)		0/265 (0%)
Infectious pleural effusion	1/282 (0.4%)		0/265 (0%)
Localised infection	0/282 (0%)		1/265 (0.4%)
Lower respiratory tract infection	0/282 (0%)		1/265 (0.4%)
Lung infection	1/282 (0.4%)		2/265 (0.8%)
Neutropenic sepsis	0/282 (0%)		3/265 (1.1%)
Ophthalmic herpes zoster	0/282 (0%)		1/265 (0.4%)
Peritonsillar abscess	1/282 (0.4%)		0/265 (0%)
Pneumocystis jirovecii pneumonia	0/282 (0%)		1/265 (0.4%)
Pneumonia	11/282 (3.9%)		4/265 (1.5%)
Post procedural infection	0/282 (0%)		1/265 (0.4%)
Pulmonary sepsis	0/282 (0%)		1/265 (0.4%)
Respiratory tract infection	3/282 (1.1%)		2/265 (0.8%)
Sepsis	1/282 (0.4%)		2/265 (0.8%)
Upper respiratory tract infection	1/282 (0.4%)		0/265 (0%)
Urinary tract infection	2/282 (0.7%)		0/265 (0%)
Injury, poisoning and procedural complications
Contusion	1/282 (0.4%)		0/265 (0%)
Femoral neck fracture	1/282 (0.4%)		0/265 (0%)
Infusion related reaction	1/282 (0.4%)		1/265 (0.4%)
Injection related reaction	1/282 (0.4%)		0/265 (0%)
Subdural haematoma	1/282 (0.4%)		0/265 (0%)
Synovial rupture	0/282 (0%)		1/265 (0.4%)
Toxicity to various agents	1/282 (0.4%)		0/265 (0%)
Investigations
Amylase increased	1/282 (0.4%)		0/265 (0%)
Aspartate aminotransferase increased	1/282 (0.4%)		0/265 (0%)
Blood creatinine increased	1/282 (0.4%)		0/265 (0%)
C-reactive protein increased	0/282 (0%)		2/265 (0.8%)
Gamma-glutamyltransferase increased	1/282 (0.4%)		0/265 (0%)
Lipase increased	2/282 (0.7%)		0/265 (0%)
Neutrophil count decreased	0/282 (0%)		4/265 (1.5%)
Platelet count decreased	2/282 (0.7%)		10/265 (3.8%)
White blood cell count decreased	0/282 (0%)		2/265 (0.8%)
Metabolism and nutrition disorders
Dehydration	1/282 (0.4%)		0/265 (0%)
Electrolyte imbalance	0/282 (0%)		1/265 (0.4%)
Glucose tolerance impaired	1/282 (0.4%)		0/265 (0%)
Hyperglycaemia	1/282 (0.4%)		0/265 (0%)
Hypokalaemia	0/282 (0%)		1/265 (0.4%)
Hyponatraemia	5/282 (1.8%)		2/265 (0.8%)
Type 1 diabetes mellitus	1/282 (0.4%)		0/265 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/282 (0.4%)		0/265 (0%)
Arthritis	1/282 (0.4%)		0/265 (0%)
Back pain	1/282 (0.4%)		1/265 (0.4%)
Bone pain	1/282 (0.4%)		0/265 (0%)
Osteonecrosis of jaw	1/282 (0.4%)		0/265 (0%)
Pain in extremity	1/282 (0.4%)		0/265 (0%)
Pathological fracture	0/282 (0%)		1/265 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/282 (0.4%)		0/265 (0%)
Epiglottic carcinoma	1/282 (0.4%)		0/265 (0%)
Malignant neoplasm progression	66/282 (23.4%)		28/265 (10.6%)
Second primary malignancy	0/282 (0%)		1/265 (0.4%)
Squamous cell carcinoma of the tongue	1/282 (0.4%)		0/265 (0%)
Tongue neoplasm	1/282 (0.4%)		0/265 (0%)
Tumour invasion	1/282 (0.4%)		0/265 (0%)
Tumour pain	0/282 (0%)		1/265 (0.4%)
Nervous system disorders
Brain oedema	1/282 (0.4%)		0/265 (0%)
Cerebellar ataxia	1/282 (0.4%)		0/265 (0%)
Cerebrovascular accident	0/282 (0%)		2/265 (0.8%)
Dizziness	1/282 (0.4%)		0/265 (0%)
Epilepsy	1/282 (0.4%)		0/265 (0%)
Haemorrhage intracranial	1/282 (0.4%)		0/265 (0%)
Headache	1/282 (0.4%)		0/265 (0%)
Hemiparesis	0/282 (0%)		1/265 (0.4%)
Lacunar infarction	1/282 (0.4%)		0/265 (0%)
Neurological symptom	0/282 (0%)		1/265 (0.4%)
Paraneoplastic neurological syndrome	1/282 (0.4%)		0/265 (0%)
Spinal cord compression	1/282 (0.4%)		1/265 (0.4%)
Syncope	1/282 (0.4%)		0/265 (0%)
Psychiatric disorders
Confusional state	1/282 (0.4%)		2/265 (0.8%)
Delirium	0/282 (0%)		1/265 (0.4%)
Disorientation	0/282 (0%)		1/265 (0.4%)
Renal and urinary disorders
Bladder dilatation	0/282 (0%)		1/265 (0.4%)
Haematuria	1/282 (0.4%)		0/265 (0%)
Renal failure	0/282 (0%)		1/265 (0.4%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/282 (0.4%)		0/265 (0%)
Atelectasis	0/282 (0%)		1/265 (0.4%)
Chronic obstructive pulmonary disease	1/282 (0.4%)		2/265 (0.8%)
Dyspnoea	6/282 (2.1%)		5/265 (1.9%)
Epistaxis	0/282 (0%)		1/265 (0.4%)
Haemoptysis	1/282 (0.4%)		3/265 (1.1%)
Hypoxia	1/282 (0.4%)		0/265 (0%)
Interstitial lung disease	2/282 (0.7%)		0/265 (0%)
Lung infiltration	0/282 (0%)		1/265 (0.4%)
Mediastinal disorder	1/282 (0.4%)		0/265 (0%)
Pleural effusion	2/282 (0.7%)		2/265 (0.8%)
Pleurisy	1/282 (0.4%)		0/265 (0%)
Pneumonia aspiration	1/282 (0.4%)		0/265 (0%)
Pneumonitis	9/282 (3.2%)		0/265 (0%)
Pneumothorax	1/282 (0.4%)		1/265 (0.4%)
Pulmonary embolism	1/282 (0.4%)		4/265 (1.5%)
Pulmonary haemorrhage	0/282 (0%)		1/265 (0.4%)
Respiratory distress	0/282 (0%)		1/265 (0.4%)
Respiratory failure	2/282 (0.7%)		2/265 (0.8%)
Skin and subcutaneous tissue disorders
Dermatitis	1/282 (0.4%)		0/265 (0%)
Paraneoplastic pemphigus	1/282 (0.4%)		0/265 (0%)
Pruritus	1/282 (0.4%)		0/265 (0%)
Stevens-Johnson syndrome	1/282 (0.4%)		0/265 (0%)
Vascular disorders
Shock	0/282 (0%)		1/265 (0.4%)
Superior vena cava syndrome	0/282 (0%)		2/265 (0.8%)
Other (Not Including Serious) Adverse Events
	Group A		Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	242/282 (85.8%)		248/265 (93.6%)
Blood and lymphatic system disorders
Anaemia	46/282 (16.3%)		159/265 (60%)
Leukopenia	9/282 (3.2%)		41/265 (15.5%)
Neutropenia	11/282 (3.9%)		88/265 (33.2%)
Thrombocytopenia	13/282 (4.6%)		77/265 (29.1%)
Endocrine disorders
Hypothyroidism	16/282 (5.7%)		0/265 (0%)
Gastrointestinal disorders
Abdominal pain upper	16/282 (5.7%)		11/265 (4.2%)
Constipation	37/282 (13.1%)		47/265 (17.7%)
Diarrhoea	28/282 (9.9%)		39/265 (14.7%)
Nausea	41/282 (14.5%)		55/265 (20.8%)
Stomatitis	9/282 (3.2%)		17/265 (6.4%)
Vomiting	26/282 (9.2%)		38/265 (14.3%)
General disorders
Asthenia	60/282 (21.3%)		59/265 (22.3%)
Fatigue	60/282 (21.3%)		73/265 (27.5%)
Pyrexia	22/282 (7.8%)		35/265 (13.2%)
Infections and infestations
Pneumonia	8/282 (2.8%)		15/265 (5.7%)
Injury, poisoning and procedural complications
Infusion related reaction	8/282 (2.8%)		16/265 (6%)
Investigations
Alanine aminotransferase increased	18/282 (6.4%)		9/265 (3.4%)
Aspartate aminotransferase increased	18/282 (6.4%)		14/265 (5.3%)
Haemoglobin decreased	4/282 (1.4%)		14/265 (5.3%)
Lipase increased	23/282 (8.2%)		3/265 (1.1%)
Neutrophil count decreased	6/282 (2.1%)		59/265 (22.3%)
Platelet count decreased	15/282 (5.3%)		61/265 (23%)
Weight decreased	21/282 (7.4%)		15/265 (5.7%)
White blood cell count decreased	11/282 (3.9%)		46/265 (17.4%)
Metabolism and nutrition disorders
Decreased appetite	71/282 (25.2%)		65/265 (24.5%)
Hypokalaemia	13/282 (4.6%)		15/265 (5.7%)
Hyponatraemia	22/282 (7.8%)		22/265 (8.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	19/282 (6.7%)		11/265 (4.2%)
Back pain	26/282 (9.2%)		23/265 (8.7%)
Pain in extremity	15/282 (5.3%)		8/265 (3%)
Nervous system disorders
Dizziness	15/282 (5.3%)		15/265 (5.7%)
Headache	26/282 (9.2%)		17/265 (6.4%)
Psychiatric disorders
Insomnia	19/282 (6.7%)		15/265 (5.7%)
Respiratory, thoracic and mediastinal disorders
Cough	59/282 (20.9%)		47/265 (17.7%)
Dyspnoea	57/282 (20.2%)		40/265 (15.1%)
Productive cough	16/282 (5.7%)		8/265 (3%)
Skin and subcutaneous tissue disorders
Alopecia	0/282 (0%)		23/265 (8.7%)
Pruritus	23/282 (8.2%)		4/265 (1.5%)
Rash	19/282 (6.7%)		10/265 (3.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.