Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Rare Diseases

Melanoma

Neoplasm Metastasis

Brain Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Vemurafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.

Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.

960 mg oral doses twice daily until disease progression, unacceptable toxicity or consent withdrawal.

Clinical Trials

This open-label, single-arm, multicenter study will evaluate the efficacy and safety in participants with metastatic melanoma who developed brain metastases. Participants may or may not have received prior systemic treatment for metastatic melanoma \[except treatment with v-raf murine sarcoma viral oncogene homolog B (BRAF) or mitogen-activated protein kinase (MEK) inhibitors\]. Participants will receive oral doses of 960 mg vemurafenib twice daily until disease progression, unacceptable toxicity or consent withdrawal.

A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases

An Open-label, Single-arm, Phase II, Multicenter Study, to Evaluate the Efficacy of Vemurafenib in Metastatic Melanoma Patients With Brain Metastases

BORR assessed by IRC is defined as percentage of participants who were responders \[with best overall response (BOR) documented as confirmed complete response (CR) or partial response (PR)\]. The RECIST v1.1 criteria modified for independent review of body and brain lesions was based on current radiology practices. The modifications to RECIST v1.1 included allowing target lesions in the brain to be \>=5 mm by contrast-enhanced magnetic resonance imaging scan (in traditional RECIST v1.1 this is \>=10 mm), allowing up to 5 target lesions in the brain (in traditional RECIST v1.1 only 2 target lesions), and examining the lesions within the brain and outside the brain separately for analytical purposes. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm), PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Percentage of participants who were responders with BOR documented as confirmed CR or PR, stable disease (SD), progressive disease (PD). CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

BORR within brain assessed by IRC is defined as percentage of participants who were responders (with BOR documented as confirmed CR or PR). According to RECIST v1.1 criteria modified for brain metastases, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm, PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

BORR outside of brain assessed by IRC is defined as percentage of participants who were responders (with BOR documented as confirmed CR or PR). According to RECIST v1.1 criteria modified for brain metastases, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm, PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Duration of response was defined as the time interval between the date of the earliest qualifying response and the earliest date of PD or death from any cause. For participants who were alive without progression following the qualifying response, DOR were censored on the date of last available tumor assessment on or before the data cutoff date.

Progression-free survival was defined as the time between enrollment on Day 1 and the date of first radiographically documented progressive disease (within or outside the brain), clinical progressive disease, as assessed by the investigator or death whichever occurred first.

Progression-free survival was defined as the time between enrollment on Day 1 and the date of first radiographically documented progressive disease (within brain), clinical progressive disease, as assessed by the investigator or death whichever occurred first.

Time to development of new lesions within the brain was defined as the interval between the date of first treatment and the earliest date of documentation of new brain lesions. Participants who were known to be free of new lesions were censored on the date of last tumor assessment.

Overall survival was defined as time between enrollment on Day 1 and date of death, irrespective of the cause of death. Participants for whom no death was captured on the clinical database were censored at the latest date they were known to be alive prior to or on the cutoff date.

Percentage of participants who were responders (with best overall response (BOR) documented as confirmed complete response \[CR\] or partial response \[PR\]) were reported.

An AE was considered 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.

Hoffmann-La Roche

The safety population included all participants who received at least one dose of study medication.

Cohort 1: Previously Untreated Participants

Cohort 2: Previously Treated Participants

Total

Age, Continuous

Sex: Female, Male

The intent-to-treat (ITT) population included all participants who were enrolled in the study.

Medical Communications

The intent to treat (ITT) population included all participants who were enrolled in the study.

Best Overall Response Rate (BORR) Within Brain of Previously Untreated Participants (Assessed by Independent Review Committee [IRC] Using Modified Response Evaluation Criteria in Solid Tumors [RECIST])

Complete Response

Partial Response

Stable Disease

Progressive Disease

Unevaluable

The ITT population included all participants who were enrolled in the study.

Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated or Untreated Brain Metastases as Assessed by the IRC Using RECIST v1.1

Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated Brain Metastases as Assessed by the IRC Using RECIST v1.1

The ITT population included all participants who were enrolled in the study. Here, number participants analyzed is the total number of participants who had measurable disease outside brain at baseline.

Best Overall Response Rate Outside the Brain (Assessed by IRC)

Investigator: DOR (Within Brain) (n=26, 13)

Investigator: DOR (Outside Brain) (n=25, 11)

IRC: DOR (Within Brain) (n=16, 10)

IRC: DOR (Outside Brain) (n=26, 9)

The ITT population included all participants who were enrolled in the study. Here, 'n' indicates number of participants who were responders within brain or outside brain assessed by investigator or IRC.

Duration of Response (DOR) (Assessed by Investigator and IRC)

Progression-Free Survival (PFS) Based on Overall Tumor Response (Assessed by Investigator)

Progression-Free Survival (PFS) Based on Tumor Assessment Within Brain Only (Assessed by Investigator )

The ITT population included all participants who were enrolled in the study. Here, number of participants analyzed is the participants who were responders.

Time to Development of New Brain Metastases in Responders

Overall Survival

Complete Response (Within Brain) (n=90, 56)

Partial Response (Within Brain) (n=90, 56)

Stable Disease (Within Brain) (n=90, 56)

Progressive Disease (Within Brain) (n=90, 56)

Unevaluable (Within Brain) (n=90, 56)

Complete Response (Outside Brain) (n=79, 40)

Partial Response (Outside Brain) (n=79, 40)

Stable Disease (Outside Brain) (n=79, 40)

Progressive Disease (Outside Brain) (n=79, 40)

Unevaluable (Outside Brain) (n=79, 40)

The ITT population included all participants who were enrolled in the study. Here, 'n' indicates the number participants who were evaluable for within brain assessment and who had measurable disease outside brain at baseline for outside brain assessment.

Spots Global Cancer Trial Database for A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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