A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01378975
First received: June 21, 2011
Last updated: June 20, 2016
Last verified: April 2016

June 21, 2011
June 20, 2016
July 2011
July 2015   (final data collection date for primary outcome 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]) [ Time Frame: Baseline up to the disease progression or death from any cause (approximately 4 years) ] [ Designated as safety issue: No ]
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.
Best Overall Response Rate (BORR) in previously untreated brain metastases (assessed by Independent Review Committee using Response Evaluation Criteria in Solid Tumors (RECIST)) [ Time Frame: Until disease progression, unacceptable toxicity or consent withdrawal (approximately 2 years) ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01378975 on ClinicalTrials.gov Archive Site
  • 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 [ Time Frame: Baseline up to the disease progression or death from any cause (approximately 4 years) ] [ Designated as safety issue: No ]
    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.
  • Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated Brain Metastases as Assessed by the IRC Using RECIST v1.1 [ Time Frame: Baseline up to the disease progression or death from any cause (approximately 4 years) ] [ Designated as safety issue: No ]
    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.
  • Best Overall Response Rate Outside the Brain (Assessed by IRC) [ Time Frame: Baseline up to the disease progression or death from any cause (approximately 4 years) ] [ Designated as safety issue: No ]
    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 (DOR) (Assessed by Investigator and IRC) [ Time Frame: Date of the earliest qualifying response until the earliest date of PD or death from any cause (approximately up to 4 years) ] [ Designated as safety issue: No ]
    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 (PFS) Based on Overall Tumor Response (Assessed by Investigator) [ Time Frame: Baseline up to the disease progression or death from any cause (approximately 4 years) ] [ Designated as safety issue: No ]
    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 (PFS) Based on Tumor Assessment Within Brain Only (Assessed by Investigator ) [ Time Frame: Baseline up to the disease progression or death from any cause (approximately 4 years) ] [ Designated as safety issue: No ]
    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 Brain Metastases in Responders [ Time Frame: Date of first treatment and the earliest date of documentation of new brain lesions (approximately up to 4 years) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline up to the disease progression or death from any cause (approximately 4 years) ] [ Designated as safety issue: No ]
    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.
  • Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator) [ Time Frame: Baseline up to the disease progression or death from any cause (approximately 4 years) ] [ Designated as safety issue: No ]
    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.
  • Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Not Necessarily Follows the RECIST Criteria - as Assessed by Investigator) [ Time Frame: Baseline up to the disease progression or death from any cause (approximately 4 years) ] [ Designated as safety issue: No ]
    Percentage of participants who were responders (with best overall response (BOR) documented as confirmed complete response [CR] or partial response [PR]) were reported.
  • Percentage of Participants With Adverse Events (AE) [ Time Frame: From signing of informed consent form up to 28 days after the last dose of study drug (approximately up to 4 years) ] [ Designated as safety issue: No ]
    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.
  • Best Overall Response Rate in previously treated or untreated brain metastases (assessed by Independent Review Committee)\n [ Time Frame: Until disease progression, unacceptable toxicity or consent withdrawal (approximately 2 years) ] [ Designated as safety issue: No ]
  • Best Overall Response Rate in previously treated brain metastases (assessed by Independent Review Committee)\n [ Time Frame: Until disease progression, unacceptable toxicity or consent withdrawal (approximately 2 years) ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events [ Time Frame: Until disease progression, unacceptable toxicity or consent withdrawal (approximately 2 years) ] [ Designated as safety issue: No ]
  • Best Overall Response Rate outside of the brain (assessed by Independent Review Committee) [ Time Frame: Until disease progression, unacceptable toxicity or consent withdrawal (approximately 2 years) ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Until disease progression, unacceptable toxicity or consent withdrawal (approximately 2 years) ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: Until disease progression, unacceptable toxicity or consent withdrawal (approximately 2 years) ] [ Designated as safety issue: No ]
  • Time to development of new brain metastases in responding patient [ Time Frame: Until disease progression, unacceptable toxicity or consent withdrawal (approximately 2 years) ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Until disease progression, unacceptable toxicity or consent withdrawal (approximately 2 years) ] [ Designated as safety issue: No ]
  • Best Overall Response Rate in brain metastases and outside of the brain (assessed by Investigator) [ Time Frame: Until disease progression, unacceptable toxicity or consent withdrawal (approximately 2 years) ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
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.
Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Malignant Melanoma
Drug: Vemurafenib
960 mg oral doses twice daily until disease progression, unacceptable toxicity or consent withdrawal.
  • Experimental: Cohort 1: Previously Untreated Participants
    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.
    Intervention: Drug: Vemurafenib
  • Experimental: Cohort 2: Previously treated Participants
    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.
    Intervention: Drug: Vemurafenib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
146
July 2015
July 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   France,   Germany,   Israel,   Italy,   Netherlands,   Spain,   United Kingdom
 
NCT01378975
MO25743
Not Provided
Not Provided
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP