A Study of Vemurafenib in Participants With Metastatic Melanoma

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01307397
• Collaborator: (none)
• Enrollment: 3,219
• Locations: 280
• Arm: 1
• Actual Duration (Months): 59.8
• Patients Per Site: 11.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This multi-center study evaluates the safety and efficacy of vemurafenib in participants with BRAF V600 mutation-positive, surgically incurable, and unresectable Stage IIIC or IV (American Joint Committee on Cancer [AJCC]) metastatic melanoma.

Condition or Disease	Intervention/Treatment	Phase
Malignant Melanoma	Drug: Vemurafenib	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 3219 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter Study to Assess the Safety of RO5185426 (Vemurafenib) in Patients With Metastatic Melanoma
• Actual Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Feb 24, 2016
• Actual Study Completion Date: Feb 24, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vemurafenib Participants will receive vemurafenib at a dose of 960 milligrams (mg) twice daily (bid) until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death, or study termination by the Sponsor, whichever occurs first.	Drug: Vemurafenib; Participants will receive continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death, or study termination by the Sponsor, whichever occurs first.; Other Names: RO5185426, Zelboraf

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Experiencing Any Grade 3 or 4 Adverse Events (AEs) as Determined by National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.0 [Baseline up to 28 days post end of treatment (maximum up to 46 months)]

   The intensity of AEs were graded on a 5-point scale (Grade 1 to 5) according to the NCI-CTCAE version 4.0, where Grade 1 indicates "Mild" severity and Grade 5 indicates "Death". The CTCAE defines Grades 3 and 4 as follows: Grade 3 means "Severe"; Inability to work or perform normal daily activity; treatment or medical intervention is indicated in order to improve the overall well-being or symptoms; delaying the onset of treatment is not putting the survival of the participant at direct risk. Grade 4 means "Life-threatening, Disabling"; based on extreme limitation in activity; significant medical intervention/therapy required; and hospitalization probable.

2. Percentage of Participants With at Least 1 AE Leading to Study Drug Interruption or Drug Discontinuation [Baseline up to 28 days post end of treatment (maximum up to 46 months)]

   An AE was considered as any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Pre existing conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. Percentage of participants with dose interruption or discontinuation due to AE was presented.

3. Percentage of Participants With AEs of Special Interest [Baseline up to 28 days post end of treatment (maximum up to 46 months)]

   AEs of special interest included cutaneous squamous cell carcinoma (SCC), rash, photosensitivity, liver injury, arthralgia, fatigue, gastrointestinal (GI) polyps, pancreatitis, potentiation of radiation toxicity, prolongation of cardiac repolarization or arrhythmia, non-cutaneous SCC and other primary malignancies (other than cutaneous SCC or new primary melanoma).

4. Mean Cumulative Dose of Vemurafenib [Baseline up to end of treatment or death (maximum up to 46 months)]

5. Duration of Vemurafenib Treatment [Baseline up to end of treatment or death (maximum upto 46 months)]

   Exposure excluding treatment interruptions: Duration during which participants actually took vemurafenib. Any time without dose-taken due to adverse events, non-compliance or any other reasons was not counted. Exposure including treatment interruptions: date of last dose - date of first dose + 1; duration during which participants actually took vemurafenib as well as duration on which medication was not taken were included in this calculation.

6. Mean Total Vemurafenib Dose Per Day [Baseline up to end of treatment or death (maximum up to 46 months)]

   Exposure excluding treatment interruptions: Duration during which participants actually took vemurafenib. Any time without dose-taken due to adverse events, non-compliance or any other reasons was not counted. Exposure including treatment interruptions: date of last dose - date of first dose + 1; duration during which participants actually took vemurafenib as well as duration on which medication was not taken were included in this calculation. Average total dose per day: total actual dose taken divided by total actual days on treatment.

7. Dose Intensity of Vemurafenib [Baseline up to end of treatment or death (maximum upto 46 months)]

   Dose intensity was defined as (total actual doses taken/total planned doses) *100, where total planned doses = prescribed doses * planned days on treatment, where planned days on treatment were defined as the interval between date of first dose and date of last dose.

Secondary Outcome Measures

1. Percentage of Participants With Improvement in Eastern Cooperative Group (ECOG) Performance Status [Baseline, Day 1 of each 28 day cycle up to end of treatment (up to 46 months)]

   ECOG Performance Status was measured on-therapy assessed participant's performance status on 5 point scale: 0 = fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (greater than [>] 50% of waking hours [hrs]), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead. Percentage of participants who had at least one point improvement from baseline at any assessment visit as well as at last study visit was reported.

2. Percentage of Participants Who Received Any Concomitant Medications [Baseline up to 46 months]

   Concomitant medications were all medications taken during the study, including those started before but ongoing at first dose. No medications for Melanoma were included. Percentage of participants who received at least one concomitant medication was reported.

3. Percentage of Participants With Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR), as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [Baseline until first documentation of confirmed CR or PR (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months])]

   BOR was assessed by the investigator according to RECIST v1.1. BOR was defined as having confirmed CR or PR. CR: disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to less than (<) 10 millimeter (mm) in short axis; PR: at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesion, and no new lesions. Confirmed responses were those that persisted on repeat imaging greater than or equal to (>=) 4 weeks after initial response.

4. Duration of Response [From 1st documentation of confirmed CR or PR to PD or death, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until end of the study [up to 46 months])]

   The duration of response was defined as the time between the date of first confirmed CR or PR and date of first progression of disease (PD), or death, from any cause. Responses were assessed as per RECIST v1.1. CR: disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to < 10 mm in short axis; PR: at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesion, and no new lesions. Confirmed responses were those that persisted on repeat imaging >= 4 weeks after initial response. PD: at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesion.

5. Time to Response [Baseline until first documentation of confirmed CR or PR, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months])]

   Time to response was defined as the time between the date of first treatment and date of first confirmed CR or PR (assessed as per RECIST v1.1). CR: disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to < 10 mm in short axis; PR: at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesion, and no new lesions. Confirmed responses were those that persisted on repeat imaging >= 4 weeks after initial response.

6. Percentage of Participants With PD Assessed According to RECIST v1.1 or Death [Baseline until PD or death, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months])]

   PD was assessed according to RECIST v1.1. PD was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesion.

7. Progression Free Survival (PFS) [Baseline until PD or death, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months])]

   PFS was defined as the time between the date of the first treatment and the date of first progression or death from any cause. PD was assessed according to RECIST v1.1. PD was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesion.

8. Percentage of Participants Who Died [Baseline until death (maximum up to 46 months)]

9. Overall Survival (OS) [Baseline until death (maximum up to 46 months)]

   Overall Survival was defined as the time from the date of first treatment to the date of death, regardless of the cause of death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants with Histologically confirmed metastatic melanoma (surgically incurable and unresectable Stage IIIC or Stage IV; AJCC) with BRAF V 600 mutation determined by Cobas 4800 BRAF Mutation Test. Unresectable Stage IIIC disease must have had confirmation from a surgical oncologist

• Participants with either measurable or non-measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1

• Participants may or may not have received prior systemic therapy for metastatic melanoma

• Eastern Cooperative Oncology Group (ECOG) performance status between 0 to 2

• Adequate hematologic, renal and liver function

Exclusion Criteria:

• Evidence of symptomatic central nervous system (CNS) lesions, use of steroids or anti-seizure medications for treatment of brain metastases prior to the first administration of vemurafenib

• Previous malignancy (other than melanoma) within the past 2 years, except for treated and controlled basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix

• Concurrent administration of any anti-cancer therapies other than those administered in the study

• Clinically significant cardiovascular disease or event within the 6 months prior to first administration of study drug

• Refractory nausea or vomiting, external biliary shunt, or significant bowel resection that would preclude adequate absorption

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University "Mother Theresa" Hospital Center; Oncology Department	Tirana		Albania	1000
2	Hospital Britanico; Oncologia	Buenos Aires		Argentina	C1280AEB
3	Fundación CIDEA	Buenos Aires		Argentina	C1425DTG
4	Inst. Alexander Fleming; Oncologia	Buenos Aires		Argentina	C1426ANZ
5	Melanoma Institute Australia	North Sydney	New South Wales	Australia	2060
6	Newcastle Mater Misericordiae Hospital; Oncology	Waratah	New South Wales	Australia	2298
7	Westmead Hospital	Westmead	New South Wales	Australia	2145
8	Border Medical Oncology	Wodonga	New South Wales	Australia	3690
9	Greenslopes Private Hospital; Gallipoli Research Centre	Greenslopes	Queensland	Australia	4120
10	The Townsville Hospital; Townsville Cancer Centre	Townsville	Queensland	Australia	4812
11	Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology	Woolloongabba	Queensland	Australia	4102
12	Royal Adelaide Hospital; Oncology	Adelaide	South Australia	Australia	5000
13	Geelong Hospital; Geelong Cardiology Practice	Geelong	Victoria	Australia	3220
14	Peter MacCallum Cancer Centre; Medical Oncology	Melbourne	Victoria	Australia	3000
15	Alfred Hospital	Melbourne	Victoria	Australia	3004
16	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
17	Landeskrankenhaus Feldkirch; Abteilung für Innere Medizin	Feldkirch		Austria	6807
18	LKH Graz; Abteilung für allgemeine Dermatologie	Graz		Austria	8036
19	LKH Innsbruck; Universitätsklinik für Dermatologie	Innsbruck		Austria	6020
20	Krankenhaus der Elisabethinen Linz; Abteilung für Dermatologie	Linz		Austria	4020
21	Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.	Salzburg		Austria	5020
22	LKH Salzburg; Universitätsklinik für Dermatologie	Salzburg		Austria	5020
23	Landesklinikum St. Pölten	St. Pölten		Austria	3100
24	Medizinische Universität Wien; Univ.Klinik für Dermatologie	Wien		Austria	1090
25	UZ Brussel	Brussel		Belgium	1090
26	Cliniques Universitaires St-Luc	Bruxelles		Belgium	1200
27	Sint Augustinus Wilrijk	Wilrijk		Belgium	2610
28	University Clinical Center of the Republic of Srpska	Banja Luka		Bosnia and Herzegovina	78000
29	Clinic of Oncology, University Clinical Center Sarajevo	Sarajevo		Bosnia and Herzegovina	71000
30	Instituto Nacional de Cancer - INCa; Pesquisa Clinica	Rio de Janeiro	RJ	Brazil	20230-130
31	Hospital das Clinicas - UFRGS	Porto Alegre	RS	Brazil	90035-003
32	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP	Brazil	01246-000
33	Hospital A. C. Camargo; Oncologia	Sao Paulo	SP	Brazil	01509-010
34	Hospital Sao Jose	São Paulo	SP	Brazil	CEP 01321-001
35	District Oncology Dispensary; Department for Oncology and Dermatology	Plovdiv		Bulgaria	4000
36	National Specialized Hospital for Active Oncology Treatment; Dermatology Clinic	Sofia		Bulgaria	1756
37	Cross Cancer Institute ; Dept of Medical Oncology	Edmonton	Alberta	Canada	T6G 1Z2
38	Lion'S Gate Hospital	North Vancouver	British Columbia	Canada	V7L 2L7
39	British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
40	St. Boniface General Hospital; Medicine	Winnipeg	Manitoba	Canada	R2H 2A6
41	QEII HSC; Oncology	Halifax	Nova Scotia	Canada	B3H 2Y9
42	Hamilton Health Sciences - Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
43	London Regional Cancer Centre	London	Ontario	Canada	N6A 4L6
44	The Ottawa Hospital; Division of Infectious Diseases	Ottawa	Ontario	Canada	K1H 8L6
45	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
46	University Health Network; Princess Margaret Hospital; Medical Oncology Dept	Toronto	Ontario	Canada	M5G 2M9
47	McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology	Montreal	Quebec	Canada	H3T 1E2
48	Chuq - Hopital Hotel Dieu de Quebec; Oncology	Quebec City	Quebec	Canada	G1R 2J6
49	Centro Javeriano de Oncología	Bogota		Colombia
50	Fundacion Santa Fe de Bogotá	Bogota		Colombia
51	Clínica Imbanaco; Oncology	Cali		Colombia
52	Hospital Pablo Tobon Uribe	Medellin-Antioquia		Colombia
53	Clinical Hospital Sisters of Mercy	Zagreb		Croatia	10000
54	Masarykův onkologický ústav; Klinika komplexní onkologické péče	Brno		Czechia	656 53
55	University Hospital; Oncology and Radiotherapy	Hradec Kralove		Czechia	500 05
56	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc		Czechia	779 00
57	Faculty Hospital; Dialysis Unit	Ostrava		Czechia	708 52
58	1 Lekarska Fakulta Uni Karlovy; 3 Interni Klinika, Labor. Pro Endokrinologii A Metabolismus	Praha		Czechia	128 00
59	Faculty Hospital Kralovske Vinohrady; Oncology	Praha		Czechia
60	Aarhus Universitetshospital; Kræftafdelingen	Aarhus C		Denmark	8000
61	Herlev Hospital; Onkologisk afdeling	Herlev		Denmark	2730
62	Odense Universitetshospital, Onkologisk Afdeling R	Odense		Denmark	5000
63	Hospital Regional Vicente Corral Moscoso, Servicio de Oncología	Cuenca		Ecuador
64	Hospital Abel Gilbert Ponton; Oncology	Guayaquil		Ecuador	EC090104
65	Hospital Solca Portoviejo; Oncologia	Portoviejo		Ecuador	EC130104
66	East Tallinn Central Hospital; Clinic of Internal Medicine	Tallinn		Estonia	11312
67	North Estonia Medical Centre Foundation; Oncology Center	Tallinn		Estonia	13419
68	Tartu University Hospital; Clinic of Hematology and Oncology	Tartu		Estonia	50406
69	Helsinki University Central Hospital; Dept of Oncology	Helsinki		Finland	00029
70	Tampere University Hospital; Dept of Oncology	Tampere		Finland	33520
71	Turku Uni Central Hospital; Oncology Clinics	Turku		Finland	20520
72	Uniklinik RWTH Aachen; Klinik für Dermatologie und Allergologie - Hautklinik	Aachen		Germany	52074
73	Klinikum Augsburg Süd; Klinik für Dermatologie und Allergologie	Augsburg		Germany	86179
74	CAMPUS BENJAMIN FRANKLIN CharitéCentrum 14 Med.Klinik f.Hämatologie u.Onkologie	Berlin		Germany	12200
75	St. Josef-Hospital Klinik f. Dermatologie u. Allergologie	Bochum		Germany	44791
76	Elbekliniken Buxtehude; Klinik für Dermatologie	Buxtehude		Germany	21614
77	DRK-Krankenhaus; Hautklinik	Chemnitz		Germany	09117
78	Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik und Poliklinik I	Dresden		Germany	01307
79	Universitätsklinikum Düsseldorf; Hautklinik	Düsseldorf		Germany	40225
80	HELIOS Klinikum Erfurt, Klinik für Hautkrankheiten und Allergologie	Erfurt		Germany	99089
81	Universitätsklinikum Erlangen; Hautklinik	Erlangen		Germany	91054
82	Universitätsklinikum Essen	Essen		Germany	45122
83	Klinik Johann Wolfgang von Goethe Uni; Klinik fuer Allgemein- und Viszeralchirurgie	Frankfurt		Germany	60596
84	Uniklinikum Freiburg Dermatol	Freiburg		Germany	79104
85	SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie	Gera		Germany	07548
86	Universitätsmedizin Göttingen Georg-August-Universität Zentrum Dermatologie	Göttingen		Germany	37075
87	Universitätsklinikum Hamburg-Eppendorf Zentrum f.Innere Medizin Klinik f.Dermatologie	Hamburg		Germany	20246
88	Medizinische Hochschule; Hautklinik Linden	Hannover		Germany	30449
89	Uni-Hautklinik	Heidelberg		Germany	69115
90	Klinikum am Gesundbrunnen; Tumorzentrum	Heilbronn		Germany	74078
91	Universitätsklinikum Jena; Klinik für Hautkrankheiten	Jena		Germany	07743
92	Klinikum Kassel; Hautklinik	Kassel		Germany	34125
93	UNI-Klinikum Campus Kiel Klinik f.Dermatologie Tagesklinik f.Dermatologie	Kiel		Germany	24105
94	Klinik der Uni zu Köln; Klinik & Poliklinik fuer Dermatologie & Venerologie	Köln		Germany	50937
95	Universitätsklinikum Leipzig Klinik f.Dermatologie Venerologie u.Allergologie	Leipzig		Germany	04103
96	Klinikum d.Stadt Ludwigshafen Hautklinik	Ludwigshafen		Germany	67063
97	Universitätsklinikum Schleswig-Holstein; Campus Lübeck	Lübeck		Germany	23538
98	Universitätsklinikum Magdeburg; Hautklinik; Klinik für Dermatologie und Venerologie	Magdeburg		Germany	39120
99	Johannes Gutenberg Unis-Klinik; Dept For Dermatology	Mainz		Germany	55131
100	Klinikum Mannheim Klinik fuer Dermatologie, Venerologie und Allergologie	Mannheim		Germany	68167
101	Universitätsklinikum Marburg Klinik f. Dermatologie	Marburg		Germany	35043
102	Johannes-Wesling-Klinikum Minden; Onkologische Ambulanz / Tagesklinik	Minden		Germany	32429
103	Klinikum der LMU München; Klinik und Poliklinik für Dermatologie und Allergologie	München		Germany	80337
104	Staedtisches Krankenhaus Muenchen-Schwabing, Haematologie & Onkolgie	München		Germany	80804
105	Universitätsklinikum Münster	Münster		Germany	48149
106	Fachklinik Hornheide; Internistische Onkologie	Münster		Germany	48157
107	Klinikum Nürnberg Nord; Hautklinik; Klinik für Dermatologie	Nürnberg		Germany	90419
108	Klinikum Dorothea Ch.Erxleben; Klinik für Dermatologie und Allergologie	Quedlinburg		Germany	06484
109	KLINIKUM VEST GmbH Knappschaftskrankenhaus Abt.Haut- Allergie- Venen- und Umwelterkrankungen	Recklinghausen		Germany	45657
110	Universitätsklinikum Regensburg; Klinik und Poliklinik für Dermatologie	Regensburg		Germany	93053
111	Universitaets-Hautklinik Tuebingen	Tübingen		Germany	72076
112	Wilhelm Fresenius Klinik; Klinik f. Dermatologie u. Allergologie	Wiesbaden		Germany	65191
113	HELIOS Klinikum Barmen Zentrum Dermatologie Allergologie und Umweltmedizin	Wuppertal		Germany	42283
114	Universitätsklinikum Würzburg; Klinik und Poliklinik für Dermatologie Venerologie u. Allergologie	Würzburg		Germany	97080
115	Laiko General Hospital; 1St Pathological Clinic	Athens		Greece	115 27
116	Hospital Hygeia; 1St Oncology Dept.	Athens		Greece	15123
117	Univ General Hosp Heraklion; Medical Oncology	Heraklion		Greece	711 10
118	Metropolitan Hospital; Dept. of Oncology	Piraeus		Greece	185 47
119	Semmelweis Egyetem; Bor-, Nemikortani es Boronkologiai Klinika	Budapest		Hungary	1085
120	Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly	Budapest		Hungary	1122
121	Debreceni Egyetem OEC; Borgyogyaszati Klinika	Debrecen		Hungary	4012
122	Pecsi Tudomanyegyetem AOK; Borgyogyaszati Klinika	Pecs		Hungary	7632
123	Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin.Kozp.	Szeged		Hungary	6720
124	Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology	New Delhi	Delhi	India	110085
125	Tata Memorial Hospital; Dept of Medical Oncology	Mumbai	Maharashtra	India	400012
126	Curie Manavata Cancer Centre	Nashik	Maharashtra	India	422004
127	Basavatarakam Indo-American Cancer Hospital & Research Institute	Hyderabad		India	500034
128	Chhatrapati Shahuji Maharaj Medical University; Department of Oncology	Lucknow		India	226003
129	Regional Cancer Centre; Dept of Oncology	Trivandrum		India	695 011
130	Christian Med Clg & Hspt	Vellore		India	632004
131	Cork Uni Hospital; Oncology Dept	Cork		Ireland
132	St Vincent'S Uni Hospital; Medical Oncology	Dublin		Ireland	4
133	Mater Misericordiae Uni Hospital; Oncology	Dublin		Ireland	7
134	Mater Private Hospital	Dublin		Ireland	7
135	St James' Hospital; Cancer Clinical Trials Office	Dublin		Ireland
136	Galway Uni Hospital; Oncology Dept	Galway		Ireland
137	University Hospital Limerick - Oncology	Limerick		Ireland
138	Waterford Regional Hospital; Department Of Medical Oncology	Waterford		Ireland
139	Soroka Medical Center; Oncology Dept	Beer Sheva		Israel	8410101
140	Ranbam Health Care Campus; Oncology - Hafia	Hafia		Israel	3109601
141	Hadassah Ein Karem Hospital; Oncology Dept	Jerusalem		Israel	91120-01
142	Chaim Sheba Medical Center; Oncology Dept	Ramat Gan		Israel	5262100
143	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli	Campania	Italy	80131
144	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna	Italy	47014
145	A.O. Universitaria Policlinico Di Modena; Oncologia	Modena	Emilia-Romagna	Italy	41100
146	AO Santa Maria Nuova; U.O. Day Hospital di Oncologi	Reggio Emilia	Emilia-Romagna	Italy	42100
147	A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia	Udine	Friuli-Venezia Giulia	Italy	33100
148	Istituto Dermopatico dell'Immacolata (IDI)-IRCCS; IV Divisione Oncologica e Dermatologia Oncologica	Roma	Lazio	Italy	00167
149	IFO - Istituto Regina Elena; Oncologia Medica	Roma	Lazio	Italy	00168
150	IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A	Genova	Liguria	Italy	16132
151	Asst Papa Giovanni XXIII; Oncologia Medica	Bergamo	Lombardia	Italy	24128
152	Az. Osp. Spedali Civili; Divisione Di Oncologia - Iii Medicina	Brescia	Lombardia	Italy	25123
153	Irccs Ospedale San Raffaele;Oncologia Medica	Milano	Lombardia	Italy	20132
154	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2	Milano	Lombardia	Italy	20133
155	Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica	Milano	Lombardia	Italy	20141
156	Policlinico Le Molinette; Clinica Dermatologica	Torino	Piemonte	Italy	10126
157	Istituto Tumori Giovanni Paolo II IRCSS; Ospedale Oncologico Bari	Bari	Puglia	Italy	70126
158	Policlinico P. Giaccone; Istituto Di Oncologia, Clinica Medica 1	Palermo	Sicilia	Italy	90127
159	Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1	Firenze	Toscana	Italy	50139
160	Azienda Ospedaliera S. Chiara; Dip di Onc,Trapianti e delle Nuove Tecnologie in Medicina	Pisa	Toscana	Italy	50126
161	A.O.U. Senese Policlinico Santa Maria Alle Scotte	Siena	Toscana	Italy	53100
162	Azienda Ospedaliera S. Maria - Terni; Oncologia	Terni	Umbria	Italy	05100
163	IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda	Padova	Veneto	Italy	35128
164	Samsung Medical Center	Seoul		Korea, Republic of	06351
165	Seoul St Mary's Hospital	Seoul		Korea, Republic of	06591
166	Seoul National University Hosp; Dept Internal Med Hem Onc	Seoul		Korea, Republic of	110-744
167	Yonsei University Severance Hospital; Medical Oncology	Seoul		Korea, Republic of	120-752
168	Asan Medical Center.	Seoul		Korea, Republic of	138-736
169	Daugavpils Regional Hospital	Daugavpils		Latvia	5417
170	Rigas Austrumu Kliniska Universitates slimnica, Latvijas Onkologijas centrs	Riga		Latvia	LV 1079
171	Klaipeda University Hospital	Klaipeda		Lithuania	92288
172	Vilnius University Hospital Santariskiu Clinic, Hematology, Oncology and Tranfusion Medicine Center	Vilnius		Lithuania	08661
173	University Clinic for Radiotherapy and Oncology Skopje; Department of skin malignancies	Skopje		Macedonia, The Former Yugoslav Republic of	1000
174	Fundación Rodolfo Padilla Padilla, A.C.; Oncology	Leon		Mexico	37000
175	Inst. Nacional de Cancerologia; Investigacion Clinica	Mexico City		Mexico	14000
176	Hospital General de México; Unidad de Oncologia	Mexico DF		Mexico	06726
177	Antoni Van Leeuwenhoek Ziekenhuis; Inwendige Geneeskunde	Amsterdam		Netherlands	1066 CX
178	VU MEDISCH CENTRUM; Dept. of Medical Oncology	Amsterdam		Netherlands	1081 HV
179	Tergooiziekenhuizen	Blaricum		Netherlands	1261 AN
180	Amphia Ziekenhuis	Breda		Netherlands	4818 CK
181	Academ Ziekenhuis Groningen; Medical Oncology	Groningen		Netherlands	9713 GZ
182	Academisch Ziekenhuis Leiden; Clinical Oncology	Leiden		Netherlands	2333 ZA
183	Academish Ziekenhuis Maastricht (Azm); Inwendige Geneeskunde	Maastricht		Netherlands	6229 HX
184	UMC St Radboud; Interne Oncologie; Medical Oncology Department	Nijmegen		Netherlands	6500 HB
185	Erasmus MC	Rotterdam		Netherlands	3000 CA
186	Universitair Medisch Centrum Utrecht; Inwendige Geneeskunde Afd.	Utrecht		Netherlands	3584 CX
187	Haukeland Universitetshospital; Onkologisk Avd.	Bergen		Norway	5021
188	The Norvegian Radium Hospital Montebello; Dept of Oncology	Oslo		Norway	0379
189	Hospital Nacional Carlos Alberto Seguin Escobedo-Essalud; Oncology & Haemathology	Arequipa		Peru	04001
190	Instituto Nacional de Enfermedades Neoplasicas	Lima		Peru	34
191	Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii	Krakow		Poland	31-531
192	ZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii;Wojska Polskiego 37	Olsztyn		Poland	10-228
193	NZOZ Med.-Polonia sp. z o.o.	Poznań		Poland	60-693
194	Centrum Onkologii- Instytut; im. M.Skłodowskiej-Curie	Warszawa		Poland	02-781
195	IPO de Lisboa; Servico de Oncologia Medica	Lisboa		Portugal	1099-023
196	IPO do Porto; Servico de Oncologia Medica	Porto		Portugal	4200-072
197	Institut of Oncology Al. Trestioreanu Bucharest; Oncology	Bucuresti		Romania	022328
198	Medisprof SRL	Cluj-Napoca		Romania	400058
199	S.C. Life Search S.R.L; Medical Oncology Clinic	Timisoara		Romania	300167
200	FSBI "Scientific Research Institute of Oncology named after N.N.Petrov" Ministry of Health of RF	St Petersburg	Leningrad	Russian Federation	197758
201	Regional Clinical Oncology Dispensary	Krasnodar		Russian Federation	350040
202	Russian Cancer Research Center	Moscow		Russian Federation	115478
203	Moscow city oncology hospital #62 of Moscow Healthcare Department	Moscow		Russian Federation	143423
204	St. Petersburg Oncology & Gynecology; City Clinical Oncology Dispensary	Saint-Petersburg		Russian Federation	197022
205	Stavropol Clinical Oncology Dispansary	Stavropol		Russian Federation	ND
206	Bashkirian Republican Clinical Oncology Dispensary	UFA		Russian Federation	450054
207	Institute for Oncology and Radiology of Serbia; Medical Oncology	Belgrade		Serbia	11000
208	Clinical Center Bezanijska Kosa; Oncology	Belgrade		Serbia	11080
209	Onkologicky ustav sv. Alzbety; Oddelenie ambulantnej chemoterapie	Bratislava		Slovakia	812 50
210	Narodny Onkologicky Ustav; Oddelenie klinickej onkologie E	Bratislava		Slovakia	833 10
211	POKO Poprad; Department of Oncology	Poprad		Slovakia	058 01
212	Institute of Oncology Ljubljana	Ljubljana		Slovenia	1000
213	Universitas Annex, University of the Free State; Clinical Oncology	Bloemfontein		South Africa	9300
214	Cape Town Oncology Trials	Cape Town		South Africa	7570
215	Cancercare	Cape Town		South Africa	7700
216	Medical Oncology Centre of Rosebank; Oncology	Johannesburg		South Africa	2196
217	Steve Biko Academic Hospital; Oncology	Pretoria		South Africa	0002
218	Sandton Oncology Centre	Sandton		South Africa	2196
219	Hospital Univ. Central de Asturias; Servicio de Oncologia	Oviedo	Asturias	Spain	33011
220	Hospital Universitario Marques de Valdecilla; Servicio de Oncologia	Santander	Cantabria	Spain	39008
221	Hospital Universitario Son Espases	Palma De Mallorca	Islas Baleares	Spain	07014
222	Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Oncologia	Las Palmas de Gran Canaria	Las Palmas	Spain	35016
223	Hospital Universitario de Santa Lucía; Servicio de Oncología Médica	Cartagena (Murcia)	Murcia	Spain	30202
224	Clinica Universitaria de Navarra; Servicio de Oncologia	Pamplona	Navarra	Spain	31008
225	Hospital Xeral Cíes; Servicio de Oncologia	Vigo	Pontevedra	Spain	36312
226	Hospital Universitario de Canarias (HUC)	La Laguna (Tenerife)	Tenerife	Spain	38320
227	Hospital de Cruces; Servicio de Oncologia	Barakaldo	Vizcaya	Spain	48903
228	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona		Spain	08035
229	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona		Spain	08036
230	Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia	Barcelona		Spain	08916
231	Hospital Reina Sofia	Cordoba		Spain	14004
232	Hospital Universitario Virgen de las Nieves; Servicio de Oncologia	Granada		Spain	18014
233	Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología	La Coruña		Spain	15006
234	Complejo Asistencial Universitario de Leon; Servicio de Oncologia	Leon		Spain	24071
235	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid		Spain	28034
236	Hospital Universitario Clínico San Carlos; Servicio de Oncologia	Madrid		Spain	28040
237	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid		Spain	28041
238	Hospital Universitario La Paz; Servicio de Oncologia	Madrid		Spain	28046
239	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga		Spain	29010
240	Hospital Regional Universitario Carlos Haya; Servicio de Oncologia	Malaga		Spain	29010
241	Hospital Clinico Universitario de Salamanca; Servicio de Oncologia	Salamanca		Spain	37007
242	Hospital Universitario Virgen Macarena; Servicio de Oncologia	Sevilla		Spain	41009
243	Hospital General Universitario de Valencia; Servicio de oncologia	Valencia		Spain	41014
244	Instituto Valenciano Oncologia; Oncologia Medica	Valencia		Spain	46009
245	Hospital Universitario Miguel Servet; Servicio Oncologia	Zaragoza		Spain	50009
246	Sahlgrenska Universitetssjukhuset; Onkology	Gothenburg		Sweden	SE-41 343
247	Skånes Onkologiska Klinik, Universitetssjukhuset	Lund		Sweden	22185
248	Karolinska Universitetssjukhuset, Solna	Stockholm		Sweden	171 76
249	Norrlands universitetssjukhus; Onkologkliniken	Umeå		Sweden
250	Akademiska sjukhuset, Onkologkliniken	Uppsala		Sweden	75185
251	Universitaetsspital Basel; Onkologie	Basel		Switzerland	4031
252	Inselspital Bern; Medizinische Onkologie	Bern		Switzerland	3010
253	Kantonsspital Graubünden;Onkologie und Hämatologie	Chur		Switzerland	7000
254	CHUV; Departement d'Oncologie	Lausanne		Switzerland	1011
255	Kantonsspital St. Gallen; Onkologie/Hämatologie	St. Gallen		Switzerland	9007
256	Universitätsspital Zürich; Dermatologische Klinik	Zürich		Switzerland	8091
257	Adana Baskent University Hospital; Medical Oncology	Adana		Turkey	01120
258	Cukurova Uni Faculty of Medicine; Medical Oncology	Adana		Turkey	01330
259	Ankara Uni , Ibn-I Sina Hospital; Oncology Dept	Ankara		Turkey	06230
260	Gazi Uni Medical Faculty Hospital; Oncology Dept	Ankara		Turkey	06500
261	Akdeniz University School of Medicine; General Surgery	Antalya		Turkey	07000
262	Ege University Medical Faculty; Medical Oncology Department	Bornova, İZMİR		Turkey	35100
263	Gaziantep University Medical Faculty, Medical Oncology Department	Gaziantep		Turkey	27310
264	Kartal Training and Research Hospital;Medical Oncology Department	Istanbul		Turkey	34000
265	Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology	Istanbul		Turkey	34300
266	American Hospital, Medical Oncology Department	Istanbul		Turkey	34365
267	Dokuz Eylul Uni ; Medical Oncology	Izmir		Turkey	35340
268	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sıhhiye, ANKARA		Turkey	06100
269	Addenbrookes Nhs Trust; Oncology Clinical Trials Unit	Cambridge		United Kingdom	CB2 0QQ
270	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 0YN
271	Royal Surrey County Hospital; St. Lukes Cancer Centre	Guildford		United Kingdom	GU2 7XX
272	St James University Hospital	Leeds		United Kingdom	LS9 7TF
273	Royal Marsden Hospital	London		United Kingdom	SW3 6JJ
274	Christie Hospital; Breast Cancer Research Office	Manchester		United Kingdom	M20 4QL
275	Northern Centre for Cancer Care Freeman Hospital; Sir Bobby Robson Cancer Trials Research Centre	Newcastle upon Tyne		United Kingdom	NE7 7DN
276	Mount Vernon Hospital; Centre For Cancer Treatment	Northwood		United Kingdom	HA6 2RN
277	Nottingham University Hospitals City Campus	Nottingham		United Kingdom	NG5 1PB
278	Churchill Hospital; Oxford Cancer and Haematology Centre	Oxford		United Kingdom	OX3 7LJ
279	Southampton General Hospital; Medical Oncology	Southampton		United Kingdom	SO16 6YD
280	Singleton Hospital; Oncology	Swansea		United Kingdom	SA2 8QA

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01307397
• Other Study ID Numbers: MO25515; 2010-023526-21
• First Posted: Mar 2, 2011
• Last Update Posted: Dec 18, 2017
• Last Verified: Jul 1, 2017

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

Study Results

Participant Flow

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 milligrams (mg) (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Period Title: Overall Study
STARTED	3219
COMPLETED	3219
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Overall Participants	3219
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.5 (14.06)
Sex: Female, Male (Count of Participants)
Female	1397 43.4%
Male	1822 56.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Experiencing Any Grade 3 or 4 Adverse Events (AEs) as Determined by National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.0
Description	The intensity of AEs were graded on a 5-point scale (Grade 1 to 5) according to the NCI-CTCAE version 4.0, where Grade 1 indicates "Mild" severity and Grade 5 indicates "Death". The CTCAE defines Grades 3 and 4 as follows: Grade 3 means "Severe"; Inability to work or perform normal daily activity; treatment or medical intervention is indicated in order to improve the overall well-being or symptoms; delaying the onset of treatment is not putting the survival of the participant at direct risk. Grade 4 means "Life-threatening, Disabling"; based on extreme limitation in activity; significant medical intervention/therapy required; and hospitalization probable.
Time Frame	Baseline up to 28 days post end of treatment (maximum up to 46 months)

Outcome Measure Data

Analysis Population Description

Safety population. Number of participants analyzed = participants with measurable disease at baseline

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	3219
Number [Percentage of participants]	52.8 1.6%

2. Primary Outcome

Title	Percentage of Participants With at Least 1 AE Leading to Study Drug Interruption or Drug Discontinuation
Description	An AE was considered as any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Pre existing conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. Percentage of participants with dose interruption or discontinuation due to AE was presented.
Time Frame	Baseline up to 28 days post end of treatment (maximum up to 46 months)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	3219
AE Leading to Drug Discontinuation	7.0 0.2%
AE Leading to Study Drug Interruption	34.0 1.1%

3. Primary Outcome

Title	Percentage of Participants With AEs of Special Interest
Description	AEs of special interest included cutaneous squamous cell carcinoma (SCC), rash, photosensitivity, liver injury, arthralgia, fatigue, gastrointestinal (GI) polyps, pancreatitis, potentiation of radiation toxicity, prolongation of cardiac repolarization or arrhythmia, non-cutaneous SCC and other primary malignancies (other than cutaneous SCC or new primary melanoma).
Time Frame	Baseline up to 28 days post end of treatment (maximum up to 46 months)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	3219
Arthralgia	42.3 1.3%
Rash	47.9 1.5%
Photosensitivity	28.4 0.9%
Fatigue	36.8 1.1%
Cutaneous SCC	14.6 0.5%
Non Cutaneous SCC	0.1 0%
New Primary Melanoma	1.7 0.1%
GI Polyps	0.03 0%
Pancreatitis	0.2 0%
Potentiation of radiation toxicity	1.4 0%
Prolongation of Cardiac Repolarization/ Arrhythmia	17.0 0.5%
Other primary malignancy	3.2 0.1%
Liver Injury	14.1 0.4%

4. Primary Outcome

Title	Mean Cumulative Dose of Vemurafenib
Time Frame	Baseline up to end of treatment or death (maximum up to 46 months)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	3219
Mean (Standard Deviation) [Grams]	501.283 (510.9121)

5. Primary Outcome

Title	Duration of Vemurafenib Treatment
Description	Exposure excluding treatment interruptions: Duration during which participants actually took vemurafenib. Any time without dose-taken due to adverse events, non-compliance or any other reasons was not counted. Exposure including treatment interruptions: date of last dose - date of first dose + 1; duration during which participants actually took vemurafenib as well as duration on which medication was not taken were included in this calculation.
Time Frame	Baseline up to end of treatment or death (maximum upto 46 months)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	3219
Exposure excluding interruptions	9.383 (9.6755)
Exposure including interruptions	9.724 (9.9072)

6. Primary Outcome

Title	Mean Total Vemurafenib Dose Per Day
Description	Exposure excluding treatment interruptions: Duration during which participants actually took vemurafenib. Any time without dose-taken due to adverse events, non-compliance or any other reasons was not counted. Exposure including treatment interruptions: date of last dose - date of first dose + 1; duration during which participants actually took vemurafenib as well as duration on which medication was not taken were included in this calculation. Average total dose per day: total actual dose taken divided by total actual days on treatment.
Time Frame	Baseline up to end of treatment or death (maximum up to 46 months)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	3219
Average Total Dose Per Day Excluding Interruptions	1.802 (0.2314)
Average Total Dose Per Day Including Interruptions	1.732 (0.2874)

7. Primary Outcome

Title	Dose Intensity of Vemurafenib
Description	Dose intensity was defined as (total actual doses taken/total planned doses) *100, where total planned doses = prescribed doses * planned days on treatment, where planned days on treatment were defined as the interval between date of first dose and date of last dose.
Time Frame	Baseline up to end of treatment or death (maximum upto 46 months)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	3219
Mean (Standard Deviation) [Percentage of planned dose]	90.21 (14.966)

8. Secondary Outcome

Title	Percentage of Participants With Improvement in Eastern Cooperative Group (ECOG) Performance Status
Description	ECOG Performance Status was measured on-therapy assessed participant's performance status on 5 point scale: 0 = fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (greater than [>] 50% of waking hours [hrs]), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead. Percentage of participants who had at least one point improvement from baseline at any assessment visit as well as at last study visit was reported.
Time Frame	Baseline, Day 1 of each 28 day cycle up to end of treatment (up to 46 months)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	3219
At Least 1 Point Improvement at Any Visit	24.7 0.8%
At Least 1 Point Improvement at Last Visit	9.9 0.3%

9. Secondary Outcome

Title	Percentage of Participants Who Received Any Concomitant Medications
Description	Concomitant medications were all medications taken during the study, including those started before but ongoing at first dose. No medications for Melanoma were included. Percentage of participants who received at least one concomitant medication was reported.
Time Frame	Baseline up to 46 months

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	3219
Number [Percentage of Participants]	93.8 2.9%

10. Secondary Outcome

Title	Percentage of Participants With Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR), as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Description	BOR was assessed by the investigator according to RECIST v1.1. BOR was defined as having confirmed CR or PR. CR: disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to less than (<) 10 millimeter (mm) in short axis; PR: at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesion, and no new lesions. Confirmed responses were those that persisted on repeat imaging greater than or equal to (>=) 4 weeks after initial response.
Time Frame	Baseline until first documentation of confirmed CR or PR (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months])

Outcome Measure Data

Analysis Population Description

Safety population. Number of participants analyzed = participants with measurable disease at baseline.

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	2982
Number (95% Confidence Interval) [Percentage of Participants]	33.4 1%

11. Secondary Outcome

Title	Duration of Response
Description	The duration of response was defined as the time between the date of first confirmed CR or PR and date of first progression of disease (PD), or death, from any cause. Responses were assessed as per RECIST v1.1. CR: disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to < 10 mm in short axis; PR: at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesion, and no new lesions. Confirmed responses were those that persisted on repeat imaging >= 4 weeks after initial response. PD: at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesion.
Time Frame	From 1st documentation of confirmed CR or PR to PD or death, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until end of the study [up to 46 months])

Outcome Measure Data

Analysis Population Description

Safety population. Number of participants analysed=participants who achieved CR or PR.

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	996
Median (95% Confidence Interval) [Months]	7.4

12. Secondary Outcome

Title	Time to Response
Description	Time to response was defined as the time between the date of first treatment and date of first confirmed CR or PR (assessed as per RECIST v1.1). CR: disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to < 10 mm in short axis; PR: at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesion, and no new lesions. Confirmed responses were those that persisted on repeat imaging >= 4 weeks after initial response.
Time Frame	Baseline until first documentation of confirmed CR or PR, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months])

Outcome Measure Data

Analysis Population Description

Safety population. Number of participants analyzed = participants with measurable disease at baseline.

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	2982
Median (Full Range) [Months]	1.84

13. Secondary Outcome

Title	Percentage of Participants With PD Assessed According to RECIST v1.1 or Death
Description	PD was assessed according to RECIST v1.1. PD was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesion.
Time Frame	Baseline until PD or death, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months])

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	3219
Number [Percentage of Participants]	87.3 2.7%

14. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS was defined as the time between the date of the first treatment and the date of first progression or death from any cause. PD was assessed according to RECIST v1.1. PD was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesion.
Time Frame	Baseline until PD or death, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months])

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	3219
Median (95% Confidence Interval) [Months]	5.6

15. Secondary Outcome

Title	Percentage of Participants Who Died
Time Frame	Baseline until death (maximum up to 46 months)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	3219
Number [Percentage of participants]	63.8 2%

16. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall Survival was defined as the time from the date of first treatment to the date of death, regardless of the cause of death.
Time Frame	Baseline until death (maximum up to 46 months)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
Measure Participants	3219
Median (95% Confidence Interval) [Months]	12.1

Adverse Events

Time Frame	Baseline up to 28 days post end of treatment (maximum up to 46 months)
Arm/Group Title	Vemurafenib
Arm/Group Description	Participants received continuous oral doses of vemurafenib 960 mg (four 240 mg tablets) twice daily in each 28-day treatment cycle until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death or study termination by the Sponsor.
All Cause Mortality
	Vemurafenib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vemurafenib
	Affected / at Risk (%)	# Events
Total	1114/3219 (34.6%)
Blood and lymphatic system disorders
Anaemia	22/3219 (0.7%)
Disseminated intravascular coagulation	2/3219 (0.1%)
Eosinophilia	1/3219 (0%)
Neutropenia	3/3219 (0.1%)
Thrombocytopenia	1/3219 (0%)
Agranulocytosis	1/3219 (0%)
Febrile neutropenia	1/3219 (0%)
Lymph node pain	1/3219 (0%)
Microcytic anaemia	2/3219 (0.1%)
Cardiac disorders
Acute myocardial infarction	10/3219 (0.3%)
Angina pectoris	5/3219 (0.2%)
Arrhythmia	1/3219 (0%)
Atrial fibrillation	15/3219 (0.5%)
Atrial flutter	4/3219 (0.1%)
Cardiac failure	6/3219 (0.2%)
Coronary artery disease	3/3219 (0.1%)
Left ventricular dysfunction	2/3219 (0.1%)
Myocardial infarction	7/3219 (0.2%)
Pericardial effusion	7/3219 (0.2%)
Pericardial haemorrhage	1/3219 (0%)
Pericarditis	7/3219 (0.2%)
Tachycardia	1/3219 (0%)
Torsade de pointes	1/3219 (0%)
Acute coronary syndrome	1/3219 (0%)
Angina unstable	2/3219 (0.1%)
Atrioventricular block	1/3219 (0%)
Cardiac arrest	2/3219 (0.1%)
Cardiac failure acute	2/3219 (0.1%)
Cardiac failure congestive	3/3219 (0.1%)
Cardiogenic shock	1/3219 (0%)
Cardiomyopathy	1/3219 (0%)
Coronary artery stenosis	1/3219 (0%)
Sinus node dysfunction	1/3219 (0%)
Supraventricular tachycardia	3/3219 (0.1%)
Ear and labyrinth disorders
Deafness	1/3219 (0%)
Vertigo	1/3219 (0%)
Hearnig impaired	1/3219 (0%)
Endocrine disorders
Hyperadrenalism	1/3219 (0%)
Eye disorders
Neovascular age-related macular degeneration	1/3219 (0%)
Diplopia	1/3219 (0%)
Iridocyclitis	3/3219 (0.1%)
Uveitis	6/3219 (0.2%)
Vitreous haemorrhage	1/3219 (0%)
Cataract	2/3219 (0.1%)
Glaucoma	2/3219 (0.1%)
Macular oedema	2/3219 (0.1%)
Papilloedema	2/3219 (0.1%)
Retinal artery occlusion	1/3219 (0%)
Retinal detachment	1/3219 (0%)
Retinopathy	1/3219 (0%)
Iritis	2/3219 (0.1%)
Gastrointestinal disorders
Abdominal distension	1/3219 (0%)
Abdominal pain	4/3219 (0.1%)
Abdominal pain lower	1/3219 (0%)
Abdominal pain upper	1/3219 (0%)
Ascites	1/3219 (0%)
Constipation	6/3219 (0.2%)
Diarrhoea	16/3219 (0.5%)
Diverticular perforation	1/3219 (0%)
Duodenal ulcer	2/3219 (0.1%)
Gastrointestinal haemorrhage	3/3219 (0.1%)
Gastrooesophageal reflux disease	2/3219 (0.1%)
Heamatemesis	1/3219 (0%)
Ileus	3/3219 (0.1%)
Inguinal hernia	3/3219 (0.1%)
Intestinal obstruction	2/3219 (0.1%)
Intestinal perforation	3/3219 (0.1%)
Jejunal perforation	1/3219 (0%)
Nausea	13/3219 (0.4%)
Oesophagitis	1/3219 (0%)
Pancreatitis	4/3219 (0.1%)
Pancreatitis acute	3/3219 (0.1%)
Small intestinal obstruction	2/3219 (0.1%)
Vomiting	17/3219 (0.5%)
Anal fistula	2/3219 (0.1%)
Anal skin tags	1/3219 (0%)
Colitis	2/3219 (0.1%)
Dyspepsia	1/3219 (0%)
Dysphagia	1/3219 (0%)
Enteroocolitis	1/3219 (0%)
Faeces pale	1/3219 (0%)
Food poisoning	1/3219 (0%)
Gastritis haemorrhagic	1/3219 (0%)
Gastrointestinal necrosis	1/3219 (0%)
Gastrointestinal toxicity	1/3219 (0%)
Haemorrhoidal haemorrhage	1/3219 (0%)
Intestinal ischaemia	1/3219 (0%)
Intussusception	1/3219 (0%)
Large intestine perforation	1/3219 (0%)
Leukoplakia oral	1/3219 (0%)
Lower gastrointestinal haemorrhage	1/3219 (0%)
Melaena	1/3219 (0%)
Mouth ulceration	1/3219 (0%)
Paraesthesia oral	1/3219 (0%)
Rectal haemorrhage	1/3219 (0%)
Retroperitoneal haematoma	1/3219 (0%)
General disorders
Chest pain	3/3219 (0.1%)
Chills	1/3219 (0%)
Chronic fatigue syndrome	1/3219 (0%)
Death	7/3219 (0.2%)
Device dislocation	1/3219 (0%)
Drug interaction	1/3219 (0%)
Fatigue	6/3219 (0.2%)
General physical health deterioration	9/3219 (0.3%)
Malaise	2/3219 (0.1%)
Multi-organ disorder	1/3219 (0%)
Multi-organ failure	2/3219 (0.1%)
Oedema	1/3219 (0%)
Oedema peripheral	1/3219 (0%)
Visceral pain	1/3219 (0%)
Pyrexia	32/3219 (1%)
Sudden cardiac death	1/3219 (0%)
Asthenia	2/3219 (0.1%)
Generalised oedema	1/3219 (0%)
Impaired healing	1/3219 (0%)
Surgical failure	1/3219 (0%)
Euthanasia	2/3219 (0.1%)
Hepatobiliary disorders
Cholecystitis acute	4/3219 (0.1%)
Cholelithiasis	1/3219 (0%)
Drug-induced liver injury	4/3219 (0.1%)
Hepatic function abnormal	1/3219 (0%)
Hepatitis	1/3219 (0%)
Hepatotoxicity	3/3219 (0.1%)
Cholangitis	1/3219 (0%)
Cholecystitis	3/3219 (0.1%)
Hepatic failure	1/3219 (0%)
Hepatitis toxic	1/3219 (0%)
Immune system disorders
Drug hypersensitivity	1/3219 (0%)
Hypersensitivity	2/3219 (0.1%)
Food allergy	1/3219 (0%)
Infections and infestations
Abscess limb	1/3219 (0%)
Anal abscess	5/3219 (0.2%)
Blastocystis infection	1/3219 (0%)
Bronchitis	1/3219 (0%)
Cellulitis	5/3219 (0.2%)
Clostridium difficile infection	1/3219 (0%)
Device related infection	4/3219 (0.1%)
Diverticulitis	2/3219 (0.1%)
Erysipelas	9/3219 (0.3%)
Escherichia bacteraemia	1/3219 (0%)
Escherichia sepsis	2/3219 (0.1%)
Gastroenteritis	4/3219 (0.1%)
Groin abscess	5/3219 (0.2%)
Herpes zoster	3/3219 (0.1%)
H1N1 influenza	1/3219 (0%)
Infection	2/3219 (0.1%)
Lower respiratory tract infection	7/3219 (0.2%)
Lung infection	6/3219 (0.2%)
Oesophageal candidiasis	3/3219 (0.1%)
Oral candidiasis	1/3219 (0%)
Otitis externa	1/3219 (0%)
Pilonidal cyst	2/3219 (0.1%)
Pharyngotonsillitis	1/3219 (0%)
Pneumocystis jiroveci pneumonia	2/3219 (0.1%)
Pneumonia	31/3219 (1%)
Postoperative wound infection	2/3219 (0.1%)
Rash pustular	1/3219 (0%)
Respiratory tract infection	7/3219 (0.2%)
Salmonella sepsis	1/3219 (0%)
Sepsis	7/3219 (0.2%)
Septic shock	1/3219 (0%)
Skin infection	1/3219 (0%)
Subcutaneous abscess	1/3219 (0%)
Upper respiratory tract infection	4/3219 (0.1%)
Urinary tract infection	11/3219 (0.3%)
Urosepsis	1/3219 (0%)
Viral infection	3/3219 (0.1%)
Vulvitis	1/3219 (0%)
Wound infection	4/3219 (0.1%)
Wound infection staphylococcal	1/3219 (0%)
Acinetobacter infection	1/3219 (0%)
Appendicitis	1/3219 (0%)
Appendicitis perforated	1/3219 (0%)
Arthritis bacterial	1/3219 (0%)
Brain Abscess	1/3219 (0%)
Atypical pneumonia	1/3219 (0%)
Cholecystitis infective	1/3219 (0%)
Colonic abscess	2/3219 (0.1%)
Cystitis	1/3219 (0%)
Gastroenteritis viral	1/3219 (0%)
Gastrointestinal infection	2/3219 (0.1%)
Hypopyon	1/3219 (0%)
Infected dermal cyst	1/3219 (0%)
Infectious pleural effusion	1/3219 (0%)
Localised infection	2/3219 (0.1%)
Lymph gland infection	1/3219 (0%)
Ophthalmic herpes zoster	1/3219 (0%)
Perineal abscess	1/3219 (0%)
Skin bacterial infection	1/3219 (0%)
Soft tissue infection	1/3219 (0%)
Subdiaphragmatic abscess	1/3219 (0%)
Tonsillitis	1/3219 (0%)
Tooth abscess	1/3219 (0%)
Tooth infection	1/3219 (0%)
Clostridium colitis	1/3219 (0%)
Injury, poisoning and procedural complications
Alcohol Poisoning	1/3219 (0%)
Fall	4/3219 (0.1%)
Femoral neck fracture	3/3219 (0.1%)
Over dose	2/3219 (0.1%)
Hip fracture	1/3219 (0%)
Post procedural haemorrhage	2/3219 (0.1%)
Radiation injury	2/3219 (0.1%)
Respiratory fume inhalation disorder	1/3219 (0%)
Spinal fracture	1/3219 (0%)
Cystitis radiation	1/3219 (0%)
Facial bone fracture	2/3219 (0.1%)
Femur fracture	4/3219 (0.1%)
Fracture	1/3219 (0%)
Fracture displacement	1/3219 (0%)
Head injury	1/3219 (0%)
Humerus fracture	1/3219 (0%)
Lumbar vertebral fracture	2/3219 (0.1%)
Multiple injuries	1/3219 (0%)
Patella fracture	1/3219 (0%)
Radiation necrosis	4/3219 (0.1%)
Radius fracture	1/3219 (0%)
Road traffic accident	1/3219 (0%)
Spinal compression fracture	1/3219 (0%)
Splenic rupture	1/3219 (0%)
Subdural haematoma	1/3219 (0%)
Sunburn	1/3219 (0%)
Tendon injury	1/3219 (0%)
Tibia fracture	1/3219 (0%)
Toxicity to various agents	2/3219 (0.1%)
Investigations
Aspartate aminotransferase increased	1/3219 (0%)
Blood creatinine increased	7/3219 (0.2%)
C-reactive protein increased	1/3219 (0%)
Gamma glutamyltransferase increased	2/3219 (0.1%)
Hepatic enzyme increased	1/3219 (0%)
Lipase increased	1/3219 (0%)
Liver function test abnormal	3/3219 (0.1%)
Blood glucose increased	2/3219 (0.1%)
Electrocardiogram QT prolonged	3/3219 (0.1%)
Metabolism and nutrition disorders
Cachexia	1/3219 (0%)
Dehydration	4/3219 (0.1%)
Diabetes mellitus	4/3219 (0.1%)
Diabetic ketoacidosis	2/3219 (0.1%)
Hyperglycaemia	2/3219 (0.1%)
Hyperuricaemia	2/3219 (0.1%)
Hypokalaemia	1/3219 (0%)
Hyponatraemia	4/3219 (0.1%)
Tumour lysis syndrome	1/3219 (0%)
Decreased appetite	1/3219 (0%)
Hypoglycaemia	4/3219 (0.1%)
Type 2 diabetes mellitus	1/3219 (0%)
Electrolyte imbalance	1/3219 (0%)
Hypertriglyceridaemia	1/3219 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	12/3219 (0.4%)
Back pain	6/3219 (0.2%)
Bursitis	1/3219 (0%)
Muscular weakness	3/3219 (0.1%)
Musculoskeletal chest pain	3/3219 (0.1%)
Arthritis	3/3219 (0.1%)
Myalgia	2/3219 (0.1%)
Neck pain	1/3219 (0%)
Osteoporosis	1/3219 (0%)
Pathological fracture	1/3219 (0%)
Dupuytren's contracture	1/3219 (0%)
Osteitis	1/3219 (0%)
Pain in extremity	1/3219 (0%)
Spinal pain	1/3219 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	68/3219 (2.1%)
Chronic lymphocytic leukaemia	1/3219 (0%)
Fibrous histiocytoma	1/3219 (0%)
Intracranial tumour haemorrhage	7/3219 (0.2%)
Keratoacanthoma	260/3219 (8.1%)
Malignant melanoma	43/3219 (1.3%)
Malignant melanoma in situ	10/3219 (0.3%)
Melanocytic naevus	2/3219 (0.1%)
Mycosis fungoides	2/3219 (0.1%)
Papilloma	4/3219 (0.1%)
Skin papilloma	3/3219 (0.1%)
Squamous cell carcinoma of skin	259/3219 (8%)
Tumour haemorrhage	1/3219 (0%)
Tumour ulceration	1/3219 (0%)
Tumour necrosis	1/3219 (0%)
Acanthoma	2/3219 (0.1%)
Adrenocarcinoma of colon	2/3219 (0.1%)
Benign neoplasm of skin	1/3219 (0%)
Bowen's disease	5/3219 (0.2%)
Breast cancer	2/3219 (0.1%)
Carcinoma in situ of skin	1/3219 (0%)
Cervix carcinoma stage 0	1/3219 (0%)
Cholesteatoma	1/3219 (0%)
Chondrosarcoma	1/3219 (0%)
Ependymoma	1/3219 (0%)
Eye naevus	1/3219 (0%)
Infected neoplasm	1/3219 (0%)
Intraductal proliferative breast lesion	1/3219 (0%)
Invasive ductal breast carcinoma	1/3219 (0%)
Kaposi's sarcoma	1/3219 (0%)
Lymphoma	1/3219 (0%)
Myxoid liposarcoma	1/3219 (0%)
Neoplasm	1/3219 (0%)
Neuroendocrine carcinoma	1/3219 (0%)
Neuroendocrine carcinoma of the skin	1/3219 (0%)
Neuroendocrine tumour	1/3219 (0%)
Oral papilloma	1/3219 (0%)
Pancreatic carcinoma	2/3219 (0.1%)
Rectal cancer	1/3219 (0%)
Seborrhoeic keratosis	1/3219 (0%)
Skin neoplasm bleeding	1/3219 (0%)
Squamous cell carcinoma of the oral cavity	1/3219 (0%)
Squamous cell carcinoma of the vulva	1/3219 (0%)
Superficial spreading melanoma stage unspecified	1/3219 (0%)
Synovial sarcoma	1/3219 (0%)
Transitional cell carcinoma	2/3219 (0.1%)
Tumour associated fever	1/3219 (0%)
Lentigo maligna	1/3219 (0%)
Nervous system disorders
Brain oedema	3/3219 (0.1%)
Cerebral haematoma	3/3219 (0.1%)
Cerebral haemorrhage	14/3219 (0.4%)
Cerebrovascular accident	10/3219 (0.3%)
Cognitive disorder	3/3219 (0.1%)
Depressed level of consciousness	1/3219 (0%)
Dizziness	3/3219 (0.1%)
Dysarthria	2/3219 (0.1%)
Epilepsy	10/3219 (0.3%)
Facial paresis	1/3219 (0%)
Generalised tonic clonic seizure	1/3219 (0%)
Haemorrhage intracranial	3/3219 (0.1%)
Haemorrhagic stroke	1/3219 (0%)
Headache	3/3219 (0.1%)
Intracranial pressure increased	1/3219 (0%)
Hydrocephalus	2/3219 (0.1%)
Ischaemic stroke	2/3219 (0.1%)
Nervous system disorder	1/3219 (0%)
Neuralgia	2/3219 (0.1%)
Neuropathy peripheral	1/3219 (0%)
Sciatica	1/3219 (0%)
Stupor	1/3219 (0%)
Syncope	2/3219 (0.1%)
Transient ischaemic attack	2/3219 (0.1%)
Tremor	1/3219 (0%)
VIIth nerve paralysis	2/3219 (0.1%)
Aphasia	1/3219 (0%)
Balance disorder	1/3219 (0%)
Carpal tunnel syndrome	1/3219 (0%)
Cerebral disorder	1/3219 (0%)
Cerebrospinal fluid leakage	1/3219 (0%)
Facial nerve disorder	1/3219 (0%)
Metabolic encephalopathy	1/3219 (0%)
Migraine	2/3219 (0.1%)
Monoplegia	1/3219 (0%)
Neurotoxicity	1/3219 (0%)
Partial seizures	1/3219 (0%)
Peripheral sensorimotor neuropathy	2/3219 (0.1%)
Polyneuropathy	1/3219 (0%)
Seizure	12/3219 (0.4%)
Simple partial seizure	1/3219 (0%)
Spinal cord compression	3/3219 (0.1%)
Status epilepticus	1/3219 (0%)
Subarachnoid haemorrhage	1/3219 (0%)
Vasogenic cerebral oedema	1/3219 (0%)
Cerebellar infarction	1/3219 (0%)
Psychiatric disorders
Anxiety	3/3219 (0.1%)
Completed suicide	2/3219 (0.1%)
Confusional state	5/3219 (0.2%)
Psychotic disorder	2/3219 (0.1%)
Suicidal ideation	1/3219 (0%)
Bipolar disorder	1/3219 (0%)
Delirium	3/3219 (0.1%)
Mania	1/3219 (0%)
Mood altered	2/3219 (0.1%)
Renal and urinary disorders
Calculus ureteric	2/3219 (0.1%)
Glomerulonephritis minimal lesion	1/3219 (0%)
Haematuria	3/3219 (0.1%)
Renal colic	2/3219 (0.1%)
Urinary tract disorder	1/3219 (0%)
Acute kidney injury	8/3219 (0.2%)
Nephrolithiasis	1/3219 (0%)
Nephropathy	1/3219 (0%)
Nephhropathy toxic	1/3219 (0%)
Tubulointerstitial nephritis	1/3219 (0%)
Urinary fistula	1/3219 (0%)
Reproductive system and breast disorders
Cervical polyp	1/3219 (0%)
Uterine haemorrhage	1/3219 (0%)
Adnexal torsion	1/3219 (0%)
Endometrial hyperplasia	1/3219 (0%)
Metrorrhagia	1/3219 (0%)
Peyronie's disease	1/3219 (0%)
Uterine cervical erosion	1/3219 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/3219 (0%)
Acute respiratory failure	4/3219 (0.1%)
Chronic obstructive pulmonary disease	4/3219 (0.1%)
Dyspnoea	4/3219 (0.1%)
Epistaxis	1/3219 (0%)
Haemoptysis	2/3219 (0.1%)
Pleural effusion	6/3219 (0.2%)
Pneumothorax	1/3219 (0%)
Pulmonary embolism	13/3219 (0.4%)
Respiratory failure	1/3219 (0%)
Acute Pulmonary Oedema	2/3219 (0.1%)
Bronchial haemorrhage	1/3219 (0%)
Hydrothorax	1/3219 (0%)
Pleurisy	1/3219 (0%)
Pleuritic pain	1/3219 (0%)
Pneumonitis	1/3219 (0%)
Pulmonary toxicity	2/3219 (0.1%)
Vocal cord leukoplakia	1/3219 (0%)
Skin and subcutaneous tissue disorders
Acanthosis	4/3219 (0.1%)
Actinic keratosis	9/3219 (0.3%)
Angioedema	2/3219 (0.1%)
Dermatitis exfoliative	3/3219 (0.1%)
Hypersensitivity vasculitis	1/3219 (0%)
Photosensitivity reaction	5/3219 (0.2%)
Rash	5/3219 (0.2%)
Rash maculo-papular	7/3219 (0.2%)
Rash pruritic	1/3219 (0%)
Skin mass	1/3219 (0%)
Toxic epidermal necrolysis	3/3219 (0.1%)
Lichenoid keratosis	1/3219 (0%)
Dermal cyst	1/3219 (0%)
Dermatitis exfoliative generalised	1/3219 (0%)
Drug eruption	2/3219 (0.1%)
Drug reaction with eosinophilia and systemic symptoms	2/3219 (0.1%)
Erythema nodosum	1/3219 (0%)
Hyperkeratosis	1/3219 (0%)
Panniculitis	2/3219 (0.1%)
Rash erythematous	1/3219 (0%)
Rash follicular	1/3219 (0%)
Rash generalised	2/3219 (0.1%)
Rash macular	1/3219 (0%)
Rash papular	1/3219 (0%)
Stevens-Johnson syndrome	1/3219 (0%)
Vascular disorders
Intermittent claudication	1/3219 (0%)
Extremity necrosis	1/3219 (0%)
Hypotension	1/3219 (0%)
Thrombophlebitis	1/3219 (0%)
Circulatory collapse	1/3219 (0%)
Deep vein thrombosis	2/3219 (0.1%)
Haematoma	1/3219 (0%)
Hypertension	2/3219 (0.1%)
Hypertensive Crisis	2/3219 (0.1%)
Other (Not Including Serious) Adverse Events
	Vemurafenib
	Affected / at Risk (%)	# Events
Total	2956/3219 (91.8%)
Blood and lymphatic system disorders
Anaemia	215/3219 (6.7%)
Gastrointestinal disorders
Diarrhoea	584/3219 (18.1%)
Nausea	718/3219 (22.3%)
Vomiting	449/3219 (13.9%)
Abdominal Pain	170/3219 (5.3%)
Constipation	196/3219 (6.1%)
General disorders
Fatigue	834/3219 (25.9%)
Pyrexia	363/3219 (11.3%)
Asthenia	382/3219 (11.9%)
Oedema Peripheral	238/3219 (7.4%)
Infections and infestations
Conjunctivitis	170/3219 (5.3%)
Nasopharyngitis	171/3219 (5.3%)
Injury, poisoning and procedural complications
Sunburn	318/3219 (9.9%)
Investigations
Weight decreased	414/3219 (12.9%)
Electrocardiogram QT prolonged	521/3219 (16.2%)
Metabolism and nutrition disorders
Decreased appetite	482/3219 (15%)
Musculoskeletal and connective tissue disorders
Arthralgia	1357/3219 (42.2%)
Myalgia	308/3219 (9.6%)
Back Pain	191/3219 (5.9%)
Muscloskeletal Pain	222/3219 (6.9%)
Pain in Extremity	276/3219 (8.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	621/3219 (19.3%)
Melanocytic naevus	227/3219 (7.1%)
Seborrhoeic keratosis	266/3219 (8.3%)
Nervous system disorders
Headache	458/3219 (14.2%)
Dysgeusia	191/3219 (5.9%)
Psychiatric disorders
Insomnia	163/3219 (5.1%)
Respiratory, thoracic and mediastinal disorders
Cough	191/3219 (5.9%)
Skin and subcutaneous tissue disorders
Alopecia	873/3219 (27.1%)
Dry skin	538/3219 (16.7%)
Erythema	327/3219 (10.2%)
Hyperkeratosis	830/3219 (25.8%)
Photosensitivity reaction	678/3219 (21.1%)
Pruritus	320/3219 (9.9%)
Rash	556/3219 (17.3%)
Actinic keratosis	246/3219 (7.6%)
Palmar plantar erythrodysaesthesia syndrome	193/3219 (6%)
Rash erythematous	195/3219 (6.1%)
Rash Maculo- Papular	179/3219 (5.6%)
Vascular disorders
Hypertension	264/3219 (8.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.