An Extension (Rollover) Study of Vemurafenib in Participants With BRAF V600 Mutation-Positive Malignancies Previously Enrolled in an Antecedent Vemurafenib Protocol

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01739764
• Collaborator: (none)
• Enrollment: 215
• Locations: 83
• Arms: 3
• Actual Duration (Months): 83.9
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This open-label, multicenter, non-randomized study provided continued access to vemurafenib for eligible participants with BRAF V600 mutation-positive malignancy, who were previously enrolled and treated in an antecedent vemurafenib protocol and did not meet the protocol's criteria for disease progression, or were treated beyond progression and were still deriving clinical benefit (as assessed by investigator), and may have therefore potentially benefited from continued treatment with vemurafenib. Participants received treatment with oral vemurafenib at 960 milligrams (mg) twice daily (BID), 720 mg BID, or 480 mg BID, depending on the last dose in the antecedent protocol. Treatment continued until progression of disease or as long as the participant was deriving clinical benefit, as judged by the investigator (case-by-case decision with approval of the Medical Monitor), death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the Sponsor to terminate the study, whichever occurred first.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms	Drug: Vemurafenib	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 215 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Extension (Rollover) Study of Vemurafenib in Patients With BRAF V600 Mutation-Positive Malignancies Previously Enrolled in an Antecedent Vemurafenib Protocol
• Actual Study Start Date: Feb 19, 2013
• Actual Primary Completion Date: Feb 17, 2020
• Actual Study Completion Date: Feb 17, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vemurafenib 480mg BID Participants received oral vemurafenib at 480 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.	Drug: Vemurafenib; Vemurafenib was given based on the last dose of the antecedent study (minimum 480 mg orally BID).; Other Names: Zelboraf
Experimental: Vemurafenib 720mg BID Participants received oral vemurafenib at 720 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.	Drug: Vemurafenib; Vemurafenib was given based on the last dose of the antecedent study (minimum 480 mg orally BID).; Other Names: Zelboraf
Experimental: Vemurafenib 960mg BID Participants received oral vemurafenib at 960 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.	Drug: Vemurafenib; Vemurafenib was given based on the last dose of the antecedent study (minimum 480 mg orally BID).; Other Names: Zelboraf

Outcome Measures

Primary Outcome Measures

1. Dose Intensity of Vemurafenib [Baseline up to a maximum of 7 years.]

   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 Adverse Events (AEs) or Serious Adverse Events (SAEs) [Baseline up to 28 days after the last dose of study drug (up to a maximum of 7 years).]

   An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as Adverse Events. Reported are the Percentage of Participants with AEs and Serious Adverse Events (SAEs).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• BRAF V600 mutation-positive malignancy

• Prior eligibility for and on study treatment from an antecedent vemurafenib protocol

• Ability to begin treatment in the extension (rollover) protocol within 15 days following the last day of the study in the antecedent protocol

• Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use 2 adequate methods of contraception as defined by protocol during the course of this study and for at least 6 months after completion of study treatment

Exclusion Criteria:

• Adverse event requiring discontinuation of vemurafenib in the antecedent protocol

• Progressive disease during the antecedent protocol. If approval to treat beyond progression was already given in the antecedent protocol, the participant may roll over into the current protocol without sponsor approval. Under special circumstances, enrollment into this protocol and dosing beyond progression may be considered and will require approval of the sponsor

Participants meeting any of the following exclusion criterion of the antecedent study at the time the participant is considered for the extension (rollover) study:

• Current, recent (within 28 days prior to Day 1), or planned use of any antitumor therapy outside this study

• Any other serious concomitant medical condition that, in the opinion of the investigator, would compromise the safety of the participant or compromise the participant's ability to participate in the study

• History of malabsorption or other clinically significant metabolic dysfunction

• History of clinically significant cardiac or pulmonary dysfunction as specified in antecedent study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Rogers	Arkansas	United States	72758
2	UCLA Department of Medicine	Los Angeles	California	United States	90024
3	Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center	Torrance	California	United States	90502
4	University of Chicago Medical Center; Medicine, Section of Pulmonary	Chicago	Illinois	United States	60637
5	Siouxland Regional Cancer Center d/b/a June E. Nylen Cancer Center	Sioux City	Iowa	United States	51108
6	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
7	New York University Medical Center PRIME	New York	New York	United States	10016
8	Evelyn H. Lauder Center	New York	New York	United States	10065
9	University of Pennsylvania Health System	Philadelphia	Pennsylvania	United States	19104
10	Mary Crowley Medical Research Center; Oncology	Dallas	Texas	United States	75246
11	M D Anderson Physician Network	Webster	Texas	United States	77598
12	University of Washington Seattle Cancer Care Alliance	Seattle	Washington	United States	98195
13	N.N. Alexandrov National Cancer Centre of Belarus	Minsk District		Belarus	223040
14	Institut Jules Bordet	Brussels		Belgium	1000
15	University Clinical Center of the Republic of Srpska	Banja Luka		Bosnia and Herzegovina	78000
16	University Clinic Centre Sarajevo	Sarajevo		Bosnia and Herzegovina	71000
17	Hospital das Clinicas - UFRGS	Porto Alegre	RS	Brazil
18	McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology	Montreal	Quebec	Canada	H3T 1E2
19	Clinical Hospital Center Sestre Milosrdnice	Zagreb		Croatia	10000
20	Clinical Hospital Centre Zagreb	Zagreb		Croatia	10000
21	Bank of Cyprus Oncology Center	Nicosia		Cyprus	2006
22	Medical Research Institute	Alexandria		Egypt	21131
23	National Cancer Institute	Cairo		Egypt	11796
24	Mansoura University Hospital	Dakahlia		Egypt	324
25	Gharbia Cancer Society	Tanta		Egypt
26	Centre Léon Bérard	Lyon		France	69373
27	Institut Gustave Roussy	Villejuif		France	94805
28	Universitätsklinikum Heidelberg	Heidelberg		Germany	69120
29	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz; Apotheke	Mainz		Germany	55131
30	Universitätsklinikum Wurzburg	Würzburg		Germany	97080
31	University General Hospital of Heraklion	Crete		Greece	711 10
32	Semmelweis Egyetem	Budapest		Hungary	1083
33	Orszagos Onkologiai Intezet	Budapest		Hungary	1122
34	Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely	Budapest		Hungary	H-1077
35	Debreceni Egyetem Klinikai Központ; Bőrgyógyászati Klinika	Debrecen		Hungary	4012
36	Pecsi Tudomanyegyetem	Pecs		Hungary	7624
37	Rambam Health Care Campus	Haifa		Israel	3109600
38	Hadassah University Hospital - Ein Kerem	Jerusalem		Israel	9112001
39	Chaim Sheba Medical Center; Allergy and Clinical Immunology Unit	Ramat Gan		Israel	5266202
40	Tel-Aviv Sourasky Medical Center	Tel Aviv		Israel	6423906
41	Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)	Milano	Lombardia	Italy
42	Azienda Ospedaliero Universitaria Pisana	Pisa	Toscana	Italy	56100
43	Kyungpook National University Chilgok Hospital	Daegu		Korea, Republic of	41404
44	Samsung Medical Center	Seoul		Korea, Republic of	(0)6351
45	Seoul National University Hospital	Seoul		Korea, Republic of	03080
46	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
47	Asan Medical Center	Seoul		Korea, Republic of	05505
48	Maastricht University Medical Center	Maastricht		Netherlands	6229 HX
49	Auckland City Hospital	Auckland		New Zealand	1023
50	Christchurch Clinical Studies Trust	Christchurch		New Zealand	8011
51	IPO de Lisboa; Servico de Oncologia Medica	Lisboa		Portugal	1099-023
52	IPO do Porto; Servico de Oncologia Medica	Porto		Portugal	4200-072
53	Medisprof SRL	Cluj-Napoca		Romania	400058
54	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"; Chemotherapy Departement	Moskva	Moskovskaja Oblast	Russian Federation	115478
55	Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic	Kazan		Russian Federation	420029
56	SBIH " Clinical Oncological Dispensary # 1"; Chemotherapy department #1 and #2	Krasnodar		Russian Federation	350040
57	Moscow city oncology hospital #62 of Moscow Healthcare Department	Moscow		Russian Federation	143423
58	St. Petersburg SHI "City Clinical Oncology Dispensary"	Saint-Petersburg		Russian Federation	197022
59	SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan	Ufa		Russian Federation	450054
60	Institute for Oncology and Radiology of Serbia; Medical Oncology	Belgrade		Serbia	11000
61	Clinical Center Bezanijska Kosa	Belgrade		Serbia	11070
62	Cape Town Oncology Trials	Cape Town		South Africa	7570
63	Wits Donald Gordon Clinical Trial Centre; Medical Oncology	Parktown, Johannesburg		South Africa	2193
64	Cancercare Langenhoven Drive Oncology Centre	Port Elizabeth		South Africa	6045
65	Hospital Universitario Marques de Valdecilla; Servicio de Oncologia	Santander	Cantabria	Spain	39008
66	Hospital Universitario Son Espases	Palma de Mallorca	Islas Baleares	Spain	07010
67	Complejo Hospitalario Universitario A Coruña	A Coruña	LA Coruña	Spain	15006
68	Hospital Regional Universitario de Malaga; Oncologia	Málaga	Malaga	Spain	29010
69	Hospital General Universitario Santa Lucia	Cartagena (Murcia)	Murcia	Spain	30202
70	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
71	Hospital Clinic i Provincial de Barcelona	Barcelona		Spain	08036
72	Hospital Universitario La Paz	Madrid		Spain	280146
73	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
74	Hospital Universitario Clínico San Carlos; Servicio de Oncologia	Madrid		Spain	28040
75	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
76	START Madrid. Centro Integral Oncologico Clara Campal; CIOCC	Madrid		Spain	28050
77	Hospital Universitario de Salamanca	Salamanca		Spain	37007
78	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
79	Instituto Valenciano Oncologia; Oncologia Medica	Valencia		Spain	46009
80	Hospital General Universitario de Valencia	Valencia		Spain	46014
81	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 0YN
82	Churchill Hospital	Oxford		United Kingdom	OX3 7LJ
83	Royal Marsden Hospital	Surrey		United Kingdom	SM2 5PT

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 20, 2018

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01739764
• Other Study ID Numbers: GO28399; 2012-003144-80
• First Posted: Dec 3, 2012
• Last Update Posted: Jan 7, 2021
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neoplasms; Vemurafenib

Study Results

Participant Flow

Recruitment Details	The study was conducted at 82 centers in 24 countries.
Pre-assignment Detail	215 participants were enrolled into this OLE study and were included in the Safety population.

Arm/Group Title	Vemurafenib 480mg BID	Vemurafenib 720mg BID	Vemurafenib 960mg BID
Arm/Group Description	Participants received oral vemurafenib at 480 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.	Participants received oral vemurafenib at 720 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.	Participants received oral vemurafenib at 960 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.
Period Title: Overall Study
STARTED	29	40	146
COMPLETED	3	4	20
NOT COMPLETED	26	36	126

Baseline Characteristics

Arm/Group Title	Vemurafenib 480mg BID	Vemurafenib 720mg BID	Vemurafenib 960mg BID	Total
Arm/Group Description	Participants received oral vemurafenib at 480 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.	Participants received oral vemurafenib at 720 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.	Participants received oral vemurafenib at 960 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.	Total of all reporting groups
Overall Participants	29	40	146	215
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.4 (11.7)	60.6 (12.4)	52.3 (13.5)	54.9 (13.6)
Sex: Female, Male (Count of Participants)
Female	18 62.1%	20 50%	57 39%	95 44.2%
Male	11 37.9%	20 50%	89 61%	120 55.8%
Race/Ethnicity, Customized (Number) [Number]
Hispanic or Latino	2 6.9%	2 5%	3 2.1%	7 3.3%
Not Hispanic or Latino	24 82.8%	37 92.5%	137 93.8%	198 92.1%
Not Stated	0 0%	0 0%	1 0.7%	1 0.5%
Unknown	3 10.3%	1 2.5%	5 3.4%	9 4.2%
Race/Ethnicity, Customized (Number) [Number]
Asian	2 6.9%	2 5%	39 26.7%	43 20%
Black or African American	1 3.4%	0 0%	0 0%	1 0.5%
White	23 79.3%	37 92.5%	101 69.2%	161 74.9%
Other	0 0%	1 2.5%	2 1.4%	3 1.4%
Unknown	3 10.3%	0 0%	4 2.7%	7 3.3%

Outcome Measures

1. 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 a maximum of 7 years.

Outcome Measure Data

Analysis Population Description

The Safety-evaluable population was defined as all participants who received at least one dose of study medication. Please note that for this Outcome Measure, one participant who received 960 mg BID of Vemurafenib had no treatment end date indicated and was excluded from the calculation of study treatment exposure summaries.

Arm/Group Title	Vemurafenib 480mg BID	Vemurafenib 720mg BID	Vemurafenib 960mg BID
Arm/Group Description	Participants received oral vemurafenib at 480 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.	Participants received oral vemurafenib at 720 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.	Participants received oral vemurafenib at 960 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.
Measure Participants	29	40	145
Mean (Standard Deviation) [Percentage of Planned Dose]	95.3 (8.1)	92.9 (12.1)	94.5 (11.0)

2. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
Description	An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as Adverse Events. Reported are the Percentage of Participants with AEs and Serious Adverse Events (SAEs).
Time Frame	Baseline up to 28 days after the last dose of study drug (up to a maximum of 7 years).

Outcome Measure Data

Analysis Population Description

The Safety-evaluable population was defined as all participants who received at least one dose of study medication.

Arm/Group Title	Vemurafenib 480mg BID	Vemurafenib 720mg BID	Vemurafenib 960mg BID
Arm/Group Description	Participants received oral vemurafenib at 480 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.	Participants received oral vemurafenib at 720 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.	Participants received oral vemurafenib at 960 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.
Measure Participants	29	40	146
AEs	93.1 321%	92.5 231.3%	93.2 63.8%
SAEs	48.3 166.6%	37.5 93.8%	19.9 13.6%

Adverse Events

Time Frame	Baseline up to 28 days after the last dose of study drug (up to a maximum of 7 years).
Arm/Group Title	Vemurafenib 480mg BID		Vemurafenib 720mg BID		Vemurafenib 960mg BID
Arm/Group Description	Participants received oral vemurafenib at 480 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.		Participants received oral vemurafenib at 720 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.		Participants received oral vemurafenib at 960 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.
All Cause Mortality
	Vemurafenib 480mg BID		Vemurafenib 720mg BID		Vemurafenib 960mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/29 (13.8%)		6/40 (15%)		38/146 (26%)
Serious Adverse Events
	Vemurafenib 480mg BID		Vemurafenib 720mg BID		Vemurafenib 960mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/29 (48.3%)		15/40 (37.5%)		29/146 (19.9%)
Blood and lymphatic system disorders
ANAEMIA	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
Cardiac disorders
ACUTE CORONARY SYNDROME	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
ARTERIOSCLEROSIS CORONARY ARTERY	0/29 (0%)	0	1/40 (2.5%)	1	0/146 (0%)	0
ATRIAL FIBRILLATION	1/29 (3.4%)	1	0/40 (0%)	0	1/146 (0.7%)	1
CARDIAC FAILURE	0/29 (0%)	0	1/40 (2.5%)	1	0/146 (0%)	0
MYOCARDIAL INFARCTION	0/29 (0%)	0	1/40 (2.5%)	1	3/146 (2.1%)	3
Eye disorders
CATARACT NUCLEAR	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
PAROPHTHALMIA	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
Gastrointestinal disorders
COLITIS ULCERATIVE	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
DIARRHOEA	0/29 (0%)	0	0/40 (0%)	0	3/146 (2.1%)	3
DIVERTICULAR PERFORATION	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
GASTRIC ULCER	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
HAEMATOCHEZIA	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
HAEMOPERITONEUM	0/29 (0%)	0	1/40 (2.5%)	1	0/146 (0%)	0
HAEMORRHOIDS	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
INTESTINAL OBSTRUCTION	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
OESOPHAGEAL STENOSIS	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
PANCREATITIS	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
PANCREATITIS ACUTE	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
RECTAL HAEMORRHAGE	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
SMALL INTESTINAL OBSTRUCTION	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
General disorders
ASTHENIA	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
DEATH	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
FATIGUE	1/29 (3.4%)	1	1/40 (2.5%)	1	0/146 (0%)	0
PYREXIA	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
Hepatobiliary disorders
JAUNDICE	0/29 (0%)	0	1/40 (2.5%)	1	0/146 (0%)	0
Infections and infestations
CELLULITIS	0/29 (0%)	0	1/40 (2.5%)	1	1/146 (0.7%)	1
CLOSTRIDIUM DIFFICILE COLITIS	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
ERYSIPELAS	0/29 (0%)	0	1/40 (2.5%)	1	0/146 (0%)	0
GASTROENTERITIS	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	2
MENINGITIS	0/29 (0%)	0	1/40 (2.5%)	1	0/146 (0%)	0
PNEUMONIA	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
POSTOPERATIVE WOUND INFECTION	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
SINUSITIS BACTERIAL	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
VIRAL UPPER RESPIRATORY TRACT INFECTION	0/29 (0%)	0	1/40 (2.5%)	1	0/146 (0%)	0
Injury, poisoning and procedural complications
FEMUR FRACTURE	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
ROAD TRAFFIC ACCIDENT	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
TRACHEAL HAEMORRHAGE	0/29 (0%)	0	1/40 (2.5%)	2	0/146 (0%)	0
Investigations
ALANINE AMINOTRANSFERASE INCREASED	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
ASPARTATE AMINOTRANSFERASE INCREASED	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
BLOOD ALKALINE PHOSPHATASE INCREASED	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
BLOOD BILIRUBIN INCREASED	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
BLOOD LACTATE DEHYDROGENASE INCREASED	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
ELECTROCARDIOGRAM QT PROLONGED	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
Metabolism and nutrition disorders
DIABETES MELLITUS	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
Musculoskeletal and connective tissue disorders
ARTHRALGIA	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
MYOPATHY TOXIC	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
NECK PAIN	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
PATHOLOGICAL FRACTURE	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
ROTATOR CUFF SYNDROME	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BRAIN NEOPLASM BENIGN	0/29 (0%)	0	1/40 (2.5%)	1	0/146 (0%)	0
BREAST CANCER	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
CEREBRAL HAEMANGIOMA	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
HEPATIC CANCER	0/29 (0%)	0	1/40 (2.5%)	1	0/146 (0%)	0
INVASIVE DUCTAL BREAST CARCINOMA	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
MALIGNANT MELANOMA	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
METASTASES TO LUNG	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
METASTATIC MALIGNANT MELANOMA	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	4
SQUAMOUS CELL CARCINOMA	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
SQUAMOUS CELL CARCINOMA OF SKIN	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
Nervous system disorders
CEREBRAL INFARCTION	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
CEREBROVASCULAR ACCIDENT	1/29 (3.4%)	3	1/40 (2.5%)	1	0/146 (0%)	0
EPILEPSY	0/29 (0%)	0	1/40 (2.5%)	1	0/146 (0%)	0
FACIAL PARALYSIS	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	2
HEADACHE	0/29 (0%)	0	1/40 (2.5%)	1	0/146 (0%)	0
HYDROCEPHALUS	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
SEIZURE	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
Psychiatric disorders
ANXIETY DISORDER	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	2
BIPOLAR DISORDER	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
COMPLETED SUICIDE	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
Renal and urinary disorders
RENAL COLIC	0/29 (0%)	0	1/40 (2.5%)	1	0/146 (0%)	0
RENAL FAILURE	0/29 (0%)	0	1/40 (2.5%)	1	0/146 (0%)	0
Respiratory, thoracic and mediastinal disorders
BRONCHOSPASM	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
DYSPNOEA	1/29 (3.4%)	2	0/40 (0%)	0	1/146 (0.7%)	1
EPISTAXIS	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
HAEMOPTYSIS	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
PNEUMONIA ASPIRATION	1/29 (3.4%)	2	0/40 (0%)	0	0/146 (0%)	0
PULMONARY EMBOLISM	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
RESPIRATORY FAILURE	1/29 (3.4%)	1	0/40 (0%)	0	0/146 (0%)	0
Surgical and medical procedures
TRACHEAL RESECTION	0/29 (0%)	0	1/40 (2.5%)	1	0/146 (0%)	0
Vascular disorders
DEEP VEIN THROMBOSIS	0/29 (0%)	0	0/40 (0%)	0	1/146 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Vemurafenib 480mg BID		Vemurafenib 720mg BID		Vemurafenib 960mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/29 (72.4%)		29/40 (72.5%)		119/146 (81.5%)
Blood and lymphatic system disorders
ANAEMIA	1/29 (3.4%)	1	5/40 (12.5%)	6	13/146 (8.9%)	18
Ear and labyrinth disorders
VERTIGO	0/29 (0%)	0	3/40 (7.5%)	3	1/146 (0.7%)	1
Eye disorders
GLAUCOMA	0/29 (0%)	0	2/40 (5%)	2	0/146 (0%)	0
UVEITIS	2/29 (6.9%)	2	2/40 (5%)	5	3/146 (2.1%)	4
VISION BLURRED	2/29 (6.9%)	2	2/40 (5%)	2	1/146 (0.7%)	1
Gastrointestinal disorders
ABDOMINAL PAIN	3/29 (10.3%)	6	4/40 (10%)	4	4/146 (2.7%)	4
ABDOMINAL PAIN UPPER	2/29 (6.9%)	2	1/40 (2.5%)	1	2/146 (1.4%)	2
CONSTIPATION	2/29 (6.9%)	2	2/40 (5%)	2	6/146 (4.1%)	7
DIARRHOEA	3/29 (10.3%)	6	3/40 (7.5%)	5	16/146 (11%)	18
DYSPEPSIA	1/29 (3.4%)	1	3/40 (7.5%)	3	8/146 (5.5%)	8
DYSPHAGIA	2/29 (6.9%)	2	1/40 (2.5%)	1	2/146 (1.4%)	2
NAUSEA	4/29 (13.8%)	4	8/40 (20%)	8	16/146 (11%)	22
VOMITING	2/29 (6.9%)	2	4/40 (10%)	5	12/146 (8.2%)	13
General disorders
ASTHENIA	3/29 (10.3%)	4	5/40 (12.5%)	5	3/146 (2.1%)	3
FATIGUE	2/29 (6.9%)	2	5/40 (12.5%)	5	28/146 (19.2%)	33
OEDEMA PERIPHERAL	0/29 (0%)	0	2/40 (5%)	2	5/146 (3.4%)	6
PYREXIA	1/29 (3.4%)	1	1/40 (2.5%)	2	9/146 (6.2%)	11
Infections and infestations
CHORIORETINITIS	2/29 (6.9%)	2	1/40 (2.5%)	1	0/146 (0%)	0
GASTROENTERITIS	0/29 (0%)	0	2/40 (5%)	2	1/146 (0.7%)	1
NASOPHARYNGITIS	2/29 (6.9%)	2	1/40 (2.5%)	1	10/146 (6.8%)	10
PNEUMONIA	2/29 (6.9%)	2	3/40 (7.5%)	3	2/146 (1.4%)	2
UPPER RESPIRATORY TRACT INFECTION	2/29 (6.9%)	3	1/40 (2.5%)	1	6/146 (4.1%)	7
URINARY TRACT INFECTION	3/29 (10.3%)	3	4/40 (10%)	5	1/146 (0.7%)	1
Injury, poisoning and procedural complications
SUNBURN	0/29 (0%)	0	2/40 (5%)	2	6/146 (4.1%)	8
Investigations
ALANINE AMINOTRANSFERASE INCREASED	0/29 (0%)	0	2/40 (5%)	3	3/146 (2.1%)	4
BLOOD BILIRUBIN INCREASED	2/29 (6.9%)	2	4/40 (10%)	9	8/146 (5.5%)	8
BLOOD CHOLESTEROL INCREASED	0/29 (0%)	0	2/40 (5%)	2	1/146 (0.7%)	2
BLOOD CREATININE INCREASED	1/29 (3.4%)	3	3/40 (7.5%)	3	8/146 (5.5%)	10
ELECTROCARDIOGRAM QT PROLONGED	0/29 (0%)	0	2/40 (5%)	2	7/146 (4.8%)	11
PLATELET COUNT DECREASED	0/29 (0%)	0	2/40 (5%)	2	0/146 (0%)	0
WEIGHT DECREASED	1/29 (3.4%)	1	1/40 (2.5%)	1	10/146 (6.8%)	10
Metabolism and nutrition disorders
DECREASED APPETITE	2/29 (6.9%)	2	3/40 (7.5%)	5	19/146 (13%)	24
DEHYDRATION	2/29 (6.9%)	2	0/40 (0%)	0	0/146 (0%)	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA	4/29 (13.8%)	4	10/40 (25%)	15	30/146 (20.5%)	41
BACK PAIN	1/29 (3.4%)	2	1/40 (2.5%)	1	9/146 (6.2%)	9
MUSCULOSKELETAL PAIN	2/29 (6.9%)	2	0/40 (0%)	0	2/146 (1.4%)	2
MYALGIA	0/29 (0%)	0	2/40 (5%)	3	6/146 (4.1%)	6
PAIN IN EXTREMITY	2/29 (6.9%)	2	2/40 (5%)	2	7/146 (4.8%)	12
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA	0/29 (0%)	0	2/40 (5%)	4	3/146 (2.1%)	3
MELANOCYTIC NAEVUS	2/29 (6.9%)	4	1/40 (2.5%)	2	4/146 (2.7%)	5
SKIN PAPILLOMA	1/29 (3.4%)	1	0/40 (0%)	0	16/146 (11%)	24
SQUAMOUS CELL CARCINOMA OF SKIN	0/29 (0%)	0	2/40 (5%)	3	7/146 (4.8%)	13
Nervous system disorders
DIZZINESS	2/29 (6.9%)	2	3/40 (7.5%)	3	2/146 (1.4%)	2
HEADACHE	0/29 (0%)	0	4/40 (10%)	4	15/146 (10.3%)	15
NEUROPATHY PERIPHERAL	2/29 (6.9%)	2	0/40 (0%)	0	2/146 (1.4%)	2
Respiratory, thoracic and mediastinal disorders
COUGH	2/29 (6.9%)	2	1/40 (2.5%)	1	10/146 (6.8%)	10
Skin and subcutaneous tissue disorders
ACTINIC KERATOSIS	2/29 (6.9%)	2	3/40 (7.5%)	3	7/146 (4.8%)	12
ALOPECIA	0/29 (0%)	0	2/40 (5%)	2	21/146 (14.4%)	21
DERMAL CYST	1/29 (3.4%)	1	2/40 (5%)	2	5/146 (3.4%)	5
DERMATITIS	0/29 (0%)	0	2/40 (5%)	2	2/146 (1.4%)	2
DRY SKIN	0/29 (0%)	0	5/40 (12.5%)	5	9/146 (6.2%)	10
ERYTHEMA	3/29 (10.3%)	5	2/40 (5%)	2	7/146 (4.8%)	13
HYPERKERATOSIS	1/29 (3.4%)	1	3/40 (7.5%)	4	20/146 (13.7%)	21
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME	2/29 (6.9%)	2	4/40 (10%)	4	12/146 (8.2%)	13
PANNICULITIS	2/29 (6.9%)	2	1/40 (2.5%)	1	3/146 (2.1%)	10
PHOTOSENSITIVITY REACTION	1/29 (3.4%)	1	2/40 (5%)	4	22/146 (15.1%)	32
PRURITUS	1/29 (3.4%)	1	3/40 (7.5%)	3	13/146 (8.9%)	15
RASH	2/29 (6.9%)	2	1/40 (2.5%)	1	14/146 (9.6%)	16
Vascular disorders
HYPERTENSION	2/29 (6.9%)	2	3/40 (7.5%)	3	8/146 (5.5%)	8

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.