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Recruitment challenges
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This is an open-label, multicenter, single-agent, phase II study of continuous oral Zelboraf (vemurafenib) in participants with locally-advanced, unresectable, stage IIIc or metastatic melanoma and activating exon 15 BRAF mutations other than V600E.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vemurafenib | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vemurafenib | Drug | Vemurafenib 960 mg BID |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Best Objective Response Rate (BORR) | 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. | Up to 42 months |
| Measure | Description | Time Frame |
|---|---|---|
| Time to BORR | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Genentech, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Arizona Cancer Center | Tucson | Arizona | 85724 | United States | ||
| UCSD Moores Cancer Center |
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| ID | Title | Description |
|---|---|---|
| FG000 | Vemurafenib | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| From start of treatment up to first documentation of confirmed CR or PR (up to 42 months) |
| Duration of Response | 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. | From date of earliest qualifying response up to date of disease progression or death (up to 42 months) |
| Progression-free Survival (PFS) | 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. | From start of treatment up to first documentation of disease progression or death (up to 42 months) |
| Overall Survival (OS) | 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. | Date of first treatment to date of death due to any cause (up to 42 months) |
| Percentage of Participants With 6-Month Survival | Baseline to Month 6 |
| Percentage of Participants With 12-Month Survival | Baseline to Month 12 |
| Number of Participants With an Adverse Event (AE) | 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. | Up to 42 months |
| La Jolla |
| California |
| 92093 |
| United States |
| UCLA School of Medicine; Hematology/Oncology | Los Angeles | California | 90095 | United States |
| The Angeles Clinic and Research Institute, Santa Monica Office | Santa Monica | California | 90025 | United States |
| University of Colorado; Anschutz Cancer Pavilion | Aurora | Colorado | 80045 | United States |
| Moffitt Cancer Center | Tampa | Florida | 33612 | United States |
| Emory University; Winship Cancer Institute | Atlanta | Georgia | 30308 | United States |
| Oncology Specialists, S.C. | Park Ridge | Illinois | 60068 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Atlantic Health System | Morristown | New Jersey | 07960 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| Mid Ohio Onc Hematology Inc | Columbus | Ohio | 43219 | United States |
| UPCI Cancer Institute; Cancer Pavillion | Pittsburgh | Pennsylvania | 15232 | United States |
| Vanderbilt Univ Medical Ctr | Nashville | Tennessee | 37232 | United States |
| Texas Oncology-Baylor Sammons Cancer Center | Dallas | Texas | 75246 | United States |
| COMPLETED |
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| NOT COMPLETED |
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Intent to treat (ITT) population defined as all enrolled participants who received any amount of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Vemurafenib | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Best Objective Response Rate (BORR) | 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. | ITT population defined as all enrolled participants who received any amount of study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 42 months |
|
|
| |||||||||||||||||||||||||
| Secondary | Time to BORR | 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. | ITT population defined as all enrolled participants who received any amount of study drug. Participants with a confirmed CR or PR were analyzed. | Posted | Median | Full Range | months | From start of treatment up to first documentation of confirmed CR or PR (up to 42 months) |
|
| ||||||||||||||||||||||||||
| Secondary | Duration of Response | 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. | ITT population defined as all enrolled participants who received any amount of study drug. Participants with a confirmed CR or PR were analyzed. | Posted | Median | Full Range | months | From date of earliest qualifying response up to date of disease progression or death (up to 42 months) |
|
| ||||||||||||||||||||||||||
| Secondary | Progression-free Survival (PFS) | 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. | ITT population defined as all enrolled participants who received any amount of study drug. | Posted | Median | Full Range | months | From start of treatment up to first documentation of disease progression or death (up to 42 months) |
|
| ||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) | 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. | ITT population defined as all enrolled participants who received any amount of study drug. | Posted | Median | 95% Confidence Interval | months | Date of first treatment to date of death due to any cause (up to 42 months) |
|
| ||||||||||||||||||||||||||
| Secondary | Percentage of Participants With 6-Month Survival | ITT population defined as all enrolled participants who received any amount of study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline to Month 6 |
|
| |||||||||||||||||||||||||||
| Secondary | Percentage of Participants With 12-Month Survival | ITT population defined as all enrolled participants who received any amount of study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline to Month 12 |
|
| |||||||||||||||||||||||||||
| Secondary | Number of Participants With an Adverse Event (AE) | 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. | Safety population defined as all enrolled participants who received any amount of vemurafenib on study. | Posted | Number | participants | Up to 42 months |
|
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From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months)
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vemurafenib | Participants received vemurafenib 960 mg orally BID. | 13 | 31 | 30 | 31 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute coronary syndrome | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
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| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
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| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
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| Keratoacanthoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
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| Hemiplegia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
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| Peripheral motor neuropathy | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
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| Vasogenic cerebral oedema | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA 18.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Chills | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Cyst | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Mass | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Nodule | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Bacterial infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Sunburn | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 18.0 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA 18.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Seborrhoeic keratosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
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| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Fibrous histiocytoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
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| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
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| Disturbance of attention | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
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| Dysaesthesia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
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| Hyperaesthesia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Actinic keratosis | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Blister | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Sebaceous hyperplasia | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Seborrhoeic dermatitis | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800-821-8590 | genentech@druginfo.com |
| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D000077484 | Vemurafenib |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
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| Title | Denominators | Categories | ||||
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