NCT01667419 · CITED IN SOURCE DOCUMENTS

A Study of Vemurafenib Adjuvant Therapy in Participants With Surgically Resected Cutaneous BRAF-Mutant Melanoma

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2019-07-23

This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of vemurafenib in participants with completely resected, cutaneous BRAF mutation-positive melanoma at high risk for recurrence. Participants will be enrolled in two separate cohorts: Cohort 1 will include participants with completely resected Stage IIC, IIIA (participants with one or more nodal metastasis greater than \[\>\] 1 millimeter \[mm\] in diameter), or IIIB cutaneous melanoma, as defined by the American Joint Committee on Cancer (AJCC) Classification, Version 7; Cohort 2 will include participants with Stage IIIC cutaneous melanoma, as defined by this classification scheme. Within each cohort, participants will be randomized (1:1 ratio) to receive vemurafenib or matching placebo over a 52-week period.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Disease-Free Survival (DFS) as Assessed Using Contrast-Enhanced Magnetic Resonance Imaging (MRI) or Contrast Enhanced Computed Tomography (CT)

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outcome · POSTED

Distant Metastasis-Free Survival (DMFS) as Assessed Using Contrast-Enhanced MRI or Contrast Enhanced CT

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Percentage of Participants With Adverse Events

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outcome · POSTED

Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Score

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outcome · POSTED

Plasma Concentration of Vemurafenib

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Histologically confirmed melanoma of cutaneous origin * Participants with BRAFV600 mutation-positive, cutaneous melanoma (either pathologic Stage IIC or Stage III according to AJCC Staging Criteria version 7 that has been completely resected * BRAF V600 mutation status of the current primary tumor or involved lymph node determined to be positive using the cobas BRAF V600 mutation test * Surgically rendered free of disease within 90 days of randomization * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy of at least 5 years * Fully recovered from the effects of any major surgery or significant traumatic injury prior to the first dose of study treatment * Adequate hematologic, hepatic, and renal function Exclusion Criteria: * History of any systemic or local therapy (e.g., chemotherapy, biologic or targeted therapy, hormonal therapy, or photodynamic therapy) for the treatment or prevention of melanoma, including interferon alpha-2b and pegylated interferon alpha-2b * History of limb perfusion therapy * History of radiotherapy for the treatment of melanoma * Invasive malignancy other than melanoma at the time of enrollment or within 5 years prior to first dose of study treatment * Family history of inherited colon cancer syndromes * Known personal history of \>3 adenomatous colorectal polyps or a personal history of adenomatous colorectal polyp(s) \>2 centimeters (cm) in size * History of or current clinical, radiographic, or pathologic evidence of in-transit metastases, satellite, or microsatellite lesions * History of or current clinical, radiographic, or pathologic evidence of recurrent lymph node involvement after resection of a primary melanoma with lymph node involvement at any time in the past * History of local and/or regional and/or distant melanoma recurrence * History or current radiographic or pathologic evidence of distant metastases * History of clinically significant cardiac or pulmonary dysfunction * Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose of study treatment * Infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib, 960 milligrams (mg) twice daily, in 28-day cycles, for up to 52 weeks
intervention Names
Drug: Vemurafenib
label
Cohort 1 Vemurafenib
type
EXPERIMENTAL
description
Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks
intervention Names
Drug: Placebo
label
Cohort 1 Placebo
type
PLACEBO_COMPARATOR
description
Participants with Stage IIIC cutaneous melanoma received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks
intervention Names
Drug: Vemurafenib
label
Cohort 2 Vemurafenib
type
EXPERIMENTAL
description
Participants with Stage IIIC cutaneous melanoma received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks
intervention Names
Drug: Placebo
label
Cohort 2 Placebo
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Cohort 1 Vemurafenib
Cohort 2 Vemurafenib
description
4 tablets of vemurafenib 240 mg each (total 960 mg) were administered orally as per the schedule specified in the respective arm.
name
Vemurafenib
other Names
RO5185426/F17, Zelboraf
type
DRUG
arm Group Labels
Cohort 1 Placebo
Cohort 2 Placebo
description
Placebo matching to vemurafenib were administered orally as per the schedule specified in the respective arm.
name
Placebo
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: DOUBLE
who Masked: PARTICIPANT
INVESTIGATOR

primary Purpose

TREATMENT

Enrollment

count: 498
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
DFS was defined as the time from randomization until the date of the first local, regional, or distant melanoma recurrence, occurrence of new primary melanoma, or death from any cause.
measure
Disease-Free Survival (DFS) as Assessed Using Contrast-Enhanced Magnetic Resonance Imaging (MRI) or Contrast Enhanced Computed Tomography (CT)
time Frame
From randomization until the date of the first local, regional, or distant melanoma recurrence, occurrence of new primary melanoma, or death from any cause (up to the April 17, 2017 data cut-off, approximately 4.5 years)

secondary Outcomes

description
DMFS was defined as the time from randomization until the date of diagnosis of distant (i.e. non-locoregional) metastases or death from any cause.
measure
Distant Metastasis-Free Survival (DMFS) as Assessed Using Contrast-Enhanced MRI or Contrast Enhanced CT
time Frame
From randomization until the date of diagnosis of distant (i.e., non-locoregional) metastases or death from any cause (up to the April 17, 2017 data cut-off, approximately 4.5 years)
description
OS is defined as the time from randomization until the date of death from any cause.
measure
Overall Survival (OS)
time Frame
From randomization until the date of death from any cause (up until 13-July-2018, approximately 6 years)
description
An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.
measure
Percentage of Participants With Adverse Events
time Frame
From randomization up to study completion or discontinuation (up until 13-July-2018, approximately 6 years)
description
European Organisation for Research and Treatment of Cancer 30-Item Quality of Life Questionnaire assesses 8 symptoms, function, financial difficulties, and a global health status/health-related quality of life (HRQoL). Most questions use a 4-point scale (1 'Not at all' to 4 'Very much';2 questions use a 7-point scale (1 'very poor' to 7 'Excellent'). Scores were averaged and transformed to a 0-100 scale. Higher scores for the function and HRQoL represent higher levels of functioning and HRQoL, higher scores for the symptom represent higher levels of symptoms/problems, higher score for financial difficulty represent higher level of perceived financial burden of treatment. Changes of 5-10 points are considered to represent a minimally important difference to participants. A positive value means an increase, and negative value means a decrease in score at the indicated time-point relative to the score at baseline (Cycle 1 Day 1).
measure
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Score
time Frame
Day 1, Day 8, Day 15, Day 22 of Cycle 1;Day 1, Day 15 of Cycle 2;Day 1 Cycles 3-13;end of treatment(up to 13 months);every 13 weeks thereafter until recurrence or occurrence of a new primary melanoma (up to 17-Apr-17 data cut-off,approximately 4.5 years)
measure
Plasma Concentration of Vemurafenib
time Frame
Pre-morning dose (0 hour [hr]) and 1 to 4 hrs post-dose on Days 1, 8, 15, and 22 of Cycle 1; pre-morning dose (0 hr) on Days 1 and 15 of Cycle 2; pre-morning dose (0 hr) on Day 1 of Cycles 3-13; at end of treatment (up to 13 months)

Full study description

brief Summary: This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of vemurafenib in participants with completely resected, cutaneous BRAF mutation-positive melanoma at high risk for recurrence. Participants will be enrolled in two separate cohorts: Cohort 1 will include participants with completely resected Stage IIC, IIIA (participants with one or more nodal metastasis greater than \[\>\] 1 millimeter \[mm\] in diameter), or IIIB cutaneous melanoma, as defined by the American Joint Committee on Cancer (AJCC) Classification, Version 7; Cohort 2 will include participants with Stage IIIC cutaneous melanoma, as defined by this classification scheme. Within each cohort, participants will be randomized (1:1 ratio) to receive vemurafenib or matching placebo over a 52-week period.

Source references

references

citation
Ascierto PA, Lewis KD, Di Giacomo AM, Demidov L, Mandala M, Bondarenko I, Herbert C, Mackiewicz A, Rutkowski P, Guminski A, Simmons B, Ye C, Hooper G, Wongchenko MJ, Goodman GR, Yan Y, Schadendorf D. Prognostic impact of baseline tumour immune infiltrate on disease-free survival in patients with completely resected, BRAFv600 mutation-positive melanoma receiving adjuvant vemurafenib. Ann Oncol. 2020 Jan;31(1):153-159. doi: 10.1016/j.annonc.2019.10.002.
pmid
31912791
type
DERIVED
citation
Maio M, Lewis K, Demidov L, Mandala M, Bondarenko I, Ascierto PA, Herbert C, Mackiewicz A, Rutkowski P, Guminski A, Goodman GR, Simmons B, Ye C, Yan Y, Schadendorf D; BRIM8 Investigators. Adjuvant vemurafenib in resected, BRAFV600 mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):510-520. doi: 10.1016/S1470-2045(18)30106-2. Epub 2018 Feb 21.
pmid
29477665
type
DERIVED

Source notices and limitations

Discovery and provenance

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gle-agent BRAF-inhibitor therapy with vemurafenib did not show improved RFS compared with placebo in the <a href="/clinicaltrials/NCT01667419">BRIM8</a> trial (NCT01667419).[<a href="#cit/section_4.23">23</a>] The benefit of immunotherapy with ipilimumab, nivolumab, and pembrolizumab has been
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#cit/section_9.26">26</a>] Single-agent BRAF-inhibitor therapy with vemurafenib did not show improved RFS compared with placebo in the <a href="/clinicaltrials/NCT01667419">BRIM8</a> trial (NCT01667419).[<a href="#cit/section_9.27">27</a>] The benefit of immunotherapy with ipilimumab, nivol
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gle-agent BRAF-inhibitor therapy with vemurafenib did not show improved RFS compared with placebo in the <a href="/clinicaltrials/NCT01667419">BRIM8</a> trial (NCT01667419).[<a href="#cit/section_9.27">27</a>] The benefit of immunotherapy with ipilimumab, nivolumab, and pembrolizumab has be
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Melanoma Treatment (PDQ®)–Health Professional Version
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Updated: May 2, 2025
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May 2, 2025
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Preserved source evidence · Not medical advice