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Study Of Zelboraf (Vemurafenib) in Patients With Locally-Advanced, Unresectable, Stage IIIc Or Metastatic Melanoma and Activating Exon 15 BRAF Mutations Other Than V600E

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ClinicalTrials.gov Identifier: NCT01586195
Recruitment Status : Terminated (Recruitment challenges)
First Posted : April 26, 2012
Results First Posted : May 25, 2017
Last Update Posted : May 25, 2017
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Malignant Melanoma
Intervention Drug: Vemurafenib
Enrollment 31
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Vemurafenib
Hide Arm/Group Description Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 milligram (mg) orally twice daily (BID) until disease progression.
Period Title: Overall Study
Started 31
Completed 5
Not Completed 26
Reason Not Completed
Death             11
Withdrawal of Consent             5
Started new anti-melanoma therapy             1
Reason not specified             9
Arm/Group Title Vemurafenib
Hide Arm/Group Description Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Overall Number of Baseline Participants 31
Hide Baseline Analysis Population Description
Intent to treat (ITT) population defined as all enrolled participants who received any amount of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 31 participants
60.0  (11.39)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants
Female
4
  12.9%
Male
27
  87.1%
1.Primary Outcome
Title Best Objective Response Rate (BORR)
Hide Description BORR was assessed by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. BORR was defined as the number of participants whose best overall response was a complete response (CR) or partial response (PR). CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a >/=30% decrease under baseline of the sum of diameters of all target lesions. BORR was summarized along with the associated exact 95% confidence interval (CI) using the method of Clopper–Pearson.
Time Frame Up to 42 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population defined as all enrolled participants who received any amount of study drug.
Arm/Group Title Vemurafenib
Hide Arm/Group Description:
Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Overall Number of Participants Analyzed 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
22.6
(9.6 to 41.1)
2.Secondary Outcome
Title Time to BORR
Hide Description In participants with a confirmed CR or PR, time to BORR was defined as the interval between the date of first treatment and the date of first documentation of confirmed CR or PR (whichever occurred first). BORR was assessed by the investigators according to RECIST v1.1. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a >/=30% decrease under baseline of the sum of diameters of all target lesions. Participants without confirmed CR or PR were censored at the date of last tumor assessment. The time to response was summarized using univariate statistics.
Time Frame From start of treatment up to first documentation of confirmed CR or PR (up to 42 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population defined as all enrolled participants who received any amount of study drug. Participants with a confirmed CR or PR were analyzed.
Arm/Group Title Vemurafenib
Hide Arm/Group Description:
Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Overall Number of Participants Analyzed 7
Median (Full Range)
Unit of Measure: months
1.7
(1.6 to 5.6)
3.Secondary Outcome
Title Duration of Response
Hide Description In participants with a confirmed CR or PR, duration of response was defined as the time interval between the date of the earliest qualifying response and the date of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a >/=30% decrease under baseline of the sum of diameters of all target lesions. PD was defined as a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesions and increase of at least 5 mm in the sum of diameters of target lesions. Duration of response was summarized using Kaplan-Meier method.
Time Frame From date of earliest qualifying response up to date of disease progression or death (up to 42 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population defined as all enrolled participants who received any amount of study drug. Participants with a confirmed CR or PR were analyzed.
Arm/Group Title Vemurafenib
Hide Arm/Group Description:
Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Overall Number of Participants Analyzed 7
Median (Full Range)
Unit of Measure: months
10.7
(3.4 to 24.9)
4.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS was assessed by the investigators according to RECIST v1.1 and defined as the time interval between the date of the first treatment dose and the date of disease progression or death due to any cause, whichever occurred first. PD was defined as a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesions and increase of at least 5 mm in the sum of diameters of target lesions. PFS was summarized using Kaplan-Meier method.
Time Frame From start of treatment up to first documentation of disease progression or death (up to 42 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population defined as all enrolled participants who received any amount of study drug.
Arm/Group Title Vemurafenib
Hide Arm/Group Description:
Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Overall Number of Participants Analyzed 31
Median (Full Range)
Unit of Measure: months
5.5
(1.7 to 26.5)
5.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from the date of first treatment to the date of death due to any cause. OS was summarized using Kaplan-Meier method.
Time Frame Date of first treatment to date of death due to any cause (up to 42 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population defined as all enrolled participants who received any amount of study drug.
Arm/Group Title Vemurafenib
Hide Arm/Group Description:
Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Overall Number of Participants Analyzed 31
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(3.1 to NA)
[1]
Median OS and upper limit of 95% confidence interval was not estimiable as they were not reached.
6.Secondary Outcome
Title Percentage of Participants With 6-Month Survival
Hide Description [Not Specified]
Time Frame Baseline to Month 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population defined as all enrolled participants who received any amount of study drug.
Arm/Group Title Vemurafenib
Hide Arm/Group Description:
Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Overall Number of Participants Analyzed 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
82.4
(62.6 to 92.3)
7.Secondary Outcome
Title Percentage of Participants With 12-Month Survival
Hide Description [Not Specified]
Time Frame Baseline to Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population defined as all enrolled participants who received any amount of study drug.
Arm/Group Title Vemurafenib
Hide Arm/Group Description:
Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Overall Number of Participants Analyzed 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
61.6
(40.0 to 77.4)
8.Secondary Outcome
Title Number of Participants With an Adverse Event (AE)
Hide Description An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Time Frame Up to 42 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population defined as all enrolled participants who received any amount of vemurafenib on study.
Arm/Group Title Vemurafenib
Hide Arm/Group Description:
Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Overall Number of Participants Analyzed 31
Measure Type: Number
Unit of Measure: participants
30
Time Frame From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months)
Adverse Event Reporting Description An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
 
Arm/Group Title Vemurafenib
Hide Arm/Group Description Participants received vemurafenib 960 mg orally BID.
All-Cause Mortality
Vemurafenib
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Vemurafenib
Affected / at Risk (%)
Total   13/31 (41.94%) 
Cardiac disorders   
Acute coronary syndrome  1  1/31 (3.23%) 
Gastrointestinal disorders   
Abdominal pain  1  1/31 (3.23%) 
Lower gastrointestinal haemorrhage  1  1/31 (3.23%) 
Injury, poisoning and procedural complications   
Fall  1  1/31 (3.23%) 
Metabolism and nutrition disorders   
Dehydration  1  1/31 (3.23%) 
Hypercalcaemia  1  1/31 (3.23%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Squamous cell carcinoma of skin  1  6/31 (19.35%) 
Basal cell carcinoma  1  1/31 (3.23%) 
Keratoacanthoma  1  1/31 (3.23%) 
Nervous system disorders   
Cerebrovascular accident  1  1/31 (3.23%) 
Hemiplegia  1  1/31 (3.23%) 
Peripheral motor neuropathy  1  1/31 (3.23%) 
Tremor  1  1/31 (3.23%) 
Vasogenic cerebral oedema  1  1/31 (3.23%) 
Respiratory, thoracic and mediastinal disorders   
Respiratory failure  1  1/31 (3.23%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vemurafenib
Affected / at Risk (%)
Total   30/31 (96.77%) 
Blood and lymphatic system disorders   
Anaemia  1  6/31 (19.35%) 
Lymphopenia  1  2/31 (6.45%) 
Thrombocytopenia  1  2/31 (6.45%) 
Eye disorders   
Vision blurred  1  3/31 (9.68%) 
Dry eye  1  2/31 (6.45%) 
Gastrointestinal disorders   
Diarrhoea  1  8/31 (25.81%) 
Nausea  1  7/31 (22.58%) 
Constipation  1  4/31 (12.90%) 
Vomiting  1  4/31 (12.90%) 
Dyspepsia  1  3/31 (9.68%) 
General disorders   
Fatigue  1  19/31 (61.29%) 
Pyrexia  1  4/31 (12.90%) 
Chills  1  2/31 (6.45%) 
Cyst  1  2/31 (6.45%) 
Mass  1  2/31 (6.45%) 
Nodule  1  2/31 (6.45%) 
Infections and infestations   
Bacterial infection  1  2/31 (6.45%) 
Nasopharyngitis  1  2/31 (6.45%) 
Injury, poisoning and procedural complications   
Sunburn  1  4/31 (12.90%) 
Investigations   
Blood creatinine increased  1  5/31 (16.13%) 
Weight decreased  1  5/31 (16.13%) 
Alanine aminotransferase increased  1  4/31 (12.90%) 
Aspartate aminotransferase increased  1  2/31 (6.45%) 
Blood bilirubin increased  1  2/31 (6.45%) 
Metabolism and nutrition disorders   
Decreased appetite  1  5/31 (16.13%) 
Hypokalaemia  1  3/31 (9.68%) 
Hyperglycaemia  1  2/31 (6.45%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  12/31 (38.71%) 
Myalgia  1  6/31 (19.35%) 
Musculoskeletal pain  1  4/31 (12.90%) 
Joint swelling  1  3/31 (9.68%) 
Pain in extremity  1  3/31 (9.68%) 
Joint range of motion decreased  1  2/31 (6.45%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Seborrhoeic keratosis  1  7/31 (22.58%) 
Skin papilloma  1  7/31 (22.58%) 
Squamous cell carcinoma of skin  1  7/31 (22.58%) 
Squamous cell carcinoma  1  4/31 (12.90%) 
Fibrous histiocytoma  1  2/31 (6.45%) 
Melanocytic naevus  1  2/31 (6.45%) 
Nervous system disorders   
Headache  1  4/31 (12.90%) 
Disturbance of attention  1  2/31 (6.45%) 
Dysaesthesia  1  2/31 (6.45%) 
Hyperaesthesia  1  2/31 (6.45%) 
Psychiatric disorders   
Anxiety  1  2/31 (6.45%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  3/31 (9.68%) 
Oropharyngeal pain  1  3/31 (9.68%) 
Cough  1  2/31 (6.45%) 
Skin and subcutaneous tissue disorders   
Rash  1  13/31 (41.94%) 
Alopecia  1  9/31 (29.03%) 
Hyperkeratosis  1  9/31 (29.03%) 
Actinic keratosis  1  6/31 (19.35%) 
Photosensitivity reaction  1  6/31 (19.35%) 
Blister  1  2/31 (6.45%) 
Dry skin  1  2/31 (6.45%) 
Palmar-plantar erythrodysaesthesia syndrome  1  2/31 (6.45%) 
Pruritus  1  2/31 (6.45%) 
Rash generalised  1  2/31 (6.45%) 
Sebaceous hyperplasia  1  2/31 (6.45%) 
Seborrhoeic dermatitis  1  2/31 (6.45%) 
Vascular disorders   
Hypertension  1  5/31 (16.13%) 
Hypotension  1  3/31 (9.68%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01586195     History of Changes
Other Study ID Numbers: ML27763
First Submitted: April 24, 2012
First Posted: April 26, 2012
Results First Submitted: July 7, 2016
Results First Posted: May 25, 2017
Last Update Posted: May 25, 2017