Clinical trial NCT01378975: A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases
Official title: An Open-label, Single-arm, Phase II, Multicenter Study, to Evaluate the Efficacy of Vemurafenib in Metastatic Melanoma Patients With Brain Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malignant Melanoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2011-06-23
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Adult participants, \>/= 18 years of age
* Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer) with BRAF V600 mutation (cobas 4800 BRAF V600 Mutation Test)
* Measurable brain metastases, defined as lesions that were accurately measured in at least one dimension (longest diameter to be recorded) as ≥0.5 cm in the brain MRI with contrast, treated or untreated
* Participants may or may not have received prior systemic therapy for metastatic melanoma and either a) have received no prior treatment for brain metastases or b) have received prior treatment for brain metastases and have progressed
* Participants may or may not have symptoms related to their brain metastases
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Participants must have recovered from all side effects of their most recent systemic or local treatment for metastatic melanoma

Exclusion Criteria:

* Increasing corticosteroid dose during the 7 days prior to first dose of study drug
* Leptomeningeal involvement in participants with no prior treatment for brain metastases
* Previous malignancy requiring active treatment 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 anticancer therapies other than those administered in the study
* Treatment with any cytotoxic, investigational drug or targeted therapy 4 weeks prior to first dose of study drug. Radiation therapy ≤1 week prior to first administration of vemurafenib; and stereotactic radiotherapy ≤1 day prior to prior to first administration of vemurafenib
* Prior treatment with BRAF or MEK inhibitors
* Clinically significant cardiovascular disease or event within the 6 months prior to first dose of study drug

Primary outcomes:
measure: 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])
timeFrame: Baseline up to the disease progression or death from any cause (approximately 4 years)
Secondary outcomes:
measure: 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
timeFrame: Baseline up to the disease progression or death from any cause (approximately 4 years)
measure: Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated Brain Metastases as Assessed by the IRC Using RECIST v1.1
timeFrame: Baseline up to the disease progression or death from any cause (approximately 4 years)
measure: Best Overall Response Rate Outside the Brain (Assessed by IRC)
timeFrame: Baseline up to the disease progression or death from any cause (approximately 4 years)
measure: Duration of Response (DOR) (Assessed by Investigator and IRC)
timeFrame: Date of the earliest qualifying response until the earliest date of PD or death from any cause (approximately up to 4 years)
measure: Progression-Free Survival (PFS) Based on Overall Tumor Response (Assessed by Investigator)
timeFrame: Baseline up to the disease progression or death from any cause (approximately 4 years)
measure: Progression-Free Survival (PFS) Based on Tumor Assessment Within Brain Only (Assessed by Investigator )
timeFrame: Baseline up to the disease progression or death from any cause (approximately 4 years)
measure: Time to Development of New Brain Metastases in Responders
timeFrame: Date of first treatment and the earliest date of documentation of new brain lesions (approximately up to 4 years)
measure: Overall Survival
timeFrame: Baseline up to the disease progression or death from any cause (approximately 4 years)
measure: Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator)
timeFrame: Baseline up to the disease progression or death from any cause (approximately 4 years)
measure: Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Not Necessarily Follows the RECIST Criteria - as Assessed by Investigator)
timeFrame: Baseline up to the disease progression or death from any cause (approximately 4 years)
measure: Percentage of Participants With Adverse Events (AE)
timeFrame: From signing of informed consent form up to 28 days after the last dose of study drug (approximately up to 4 years)
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Tampa
country: United States
state: Florida
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Rochester
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Charlotte
country: United States
state: North Carolina
city: Dallas
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Wentworthville
country: Australia
state: New South Wales
city: Melbourne
country: Australia
state: Victoria
city: Toronto
country: Canada
state: Ontario
city: Bordeaux
country: France
city: Nice
country: France
city: Paris
country: France
city: Paris
country: France
city: Essen
country: Germany
city: Frankfurt
country: Germany
city: Kiel
country: Germany
city: Mannheim
country: Germany
city: Münster
country: Germany
city: Tübingen
country: Germany
city: Tel-Hashomer
country: Israel
city: Milano
country: Italy
state: Lombardia
city: Siena
country: Italy
state: Toscana
city: Amsterdam
country: Netherlands
city: Groningen
country: Netherlands
city: Pamplona
country: Spain
state: Navarra
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Northwood
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: