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Malignant MelanomaPhase 1NCT01519323

BRIM-P: A Study of Vemurafenib in Pediatric Patients With Stage IIIC or Stage IV Melanoma Harboring BRAFV600 Mutations

A Phase 1 study testing vemurafenib in people with Malignant Melanoma, run by Hoffmann-La Roche at 26 sites in 10 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This open-label, multicenter. single arm Phase I dose-escalation study with efficacy tail extension will evaluate the maximum tolerated dose/recommended dose, the safety and efficacy of vemurafenib (RO5185426) in pediatric participants (aged 12 through 17) with newly diagnosed or recurrent surgically incurable and… Read more about this study

Who is it for?
Ages 12 to 17 years
Conditions the study is for
Malignant Melanoma
What is being tested?
vemurafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
26 sitesin 10 countries
Study dates
Jan 2013to Dec 2015
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Pediatric participants, 12 to 17 years of age inclusive
  • Histologically confirmed surgically incurable and unresectable Stage IIIC or Stage IV (AJCC) melanoma
  • Positive proto-oncogene B-Raf (BRAF) mutation result (Cobas 4800 BRAF V600 Mutation Test)
  • Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria
  • Performance status: Karnofsky (for participants >/= 16 years of age) or Lansky (for participants < 16 years of age) score of >/= 60
  • Adequate bone marrow, liver and renal function
  • Participants must have fully recovered from the acute toxic effects of all prior therapy prior to first administration of study drug

Who cannot join

  • Active or untreated central nervous system (CNS) lesions
  • History of or known spinal cord compression or carcinomatous meningitis
  • Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study
  • Previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ, and carcinoma in-situ of the cervix
  • Previous treatment with selective/specific BRAF or Methyl Ethyl Ketone (MEK) inhibitor (previous treatment with sorafenib is allowed)
  • Any previous treatment with study drug (RO5185426) or participation in a clinical trial that includes RO5185426
  • Pregnant or lactating females
  • Known human immunodeficiency virus (HIV) positivity or acquired immune deficiency syndrome (AIDS)-related illness, active hepatitis B virus, or active hepatitis C virus

Trial locations and contacts

26 sites in 10 countries.

26 sites in 10 countries

United States8 sites

  • Study site

    Aurora, Colorado, 80045

  • Study site

    Bethesda, Maryland, 20892

  • Study site

    Boston, Massachusetts, 02115

  • Study site

    Houston, Texas, 77030

  • Study site

    Los Angeles, California, 90027

  • Study site

    Memphis, Tennessee, 38105

  • Study site

    New York, New York, 10065

  • Study site

    Saint Petersburgh, Florida, 33701

Other trials in United States

Germany3 sites

  • Study site

    Kiel, 24116

  • Study site

    Mainz, 55101

  • Study site

    Tübingen, 72076

Other trials in Germany

Italy3 sites

  • Study site

    Genoa, Liguria, 16147

  • Study site

    Milan, Lombardy, 20133

  • Study site

    Rome, Lazio, 00165

Other trials in Italy

Australia2 sites

  • Study site

    Brisbane, Queensland, 4029

  • Study site

    Westmead, New South Wales, 2145

Other trials in Australia

France2 sites

  • Study site

    Marseille, 13385

  • Study site

    Pierre-Bénite, 69495

Other trials in France

Israel2 sites

  • Study site

    Jerusalem, 9112001

  • Study site

    Petah Tikva, 49100

Other trials in Israel

Spain2 sites

  • Study site

    Esplugues de Llobregas, Barcelona, 08950

  • Study site

    Seville, Sevilla, 41013

Other trials in Spain

United Kingdom2 sites

  • Study site

    Newcastle upon Tyne, NE1 4LP

  • Study site

    Sutton, SM2 5PT

Other trials in United Kingdom

Poland1 site

  • Study site

    Wroclaw, 50-367

Other trials in Poland

Slovakia1 site

  • Study site

    Bratislava, 83340

Other trials in Slovakia

About this study

Official title: An Open-label, Multicenter, Single-arm, Phase I Dose-escalation With Efficacy Tail Extension Study of Vemurafenib (RO5185426) in Pediatric Patients With Surgically Incurable and Unresectable Stage IIIC or Stage IV Melanoma Harboring BRAFV600 Mutations

This open-label, multicenter. single arm Phase I dose-escalation study with efficacy tail extension will evaluate the maximum tolerated dose/recommended dose, the safety and efficacy of vemurafenib (RO5185426) in pediatric participants (aged 12 through 17) with newly diagnosed or recurrent surgically incurable and unresectable Stage IIIC or Stage IV melanoma harboring BRAFV600 mutations. Participants will receive vemurafenib orally twice daily until disease progression or unacceptable toxicity occurs.

Being tested
vemurafenib
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • vemurafenibDrug

    Also called Zelboraf

    Cohort 1 (participants >=45 kg): starting dose level 720mg; next dose level 960 mg Cohort 2 (participants <45 kg): starting dose 480 mg

Study groups in NCT01519323
Study groupRoleWhat they receive
VemurafenibExperimentalParticipants received vemurafenib into two separate cohorts with different starting doses based on greater than or equal to (>=)45 kilogram (kg) and other weighing less than (<)45 kg. The starting dose for participants (>=45 kg) was 720 milligram (mg) of vemurafenib by mouth twice daily (BID) and the next dose level for participants in this cohort was 960 mg by mouth BID. The starting dose level for participants weighing <45 kg was to be 480 mg of vemurafenib by mouth BID, but no participants were enrolled into this cohort.
Receives: Drug: vemurafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD)/Recommended Dose

    The MTD was defined as the dose level at which six evaluable participants had been treated and at most one participant experienced a dose limiting toxicity (DLT) and the next highest dose level was too toxic. Dose escalation occurred if 0 out of 3 or at most 1 out of 6 participant experienced DLT while being treated at a dose level; otherwise the dose was declared unsafe and thus above the MTD.

    Measured: Up to 28 days of treatment

Secondary outcomes (6)

  1. Area Under the Concentration-Time Curve for Vemurafenib

    Measured: Pre-dose, 2, 4, 8, 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 22 (each cycle is of 28 days)

  2. Number of Participants With an Adverse Event (AE)

    An AE was defined as any untoward medical occurrence in a patient administered a pharmaceutical product and which did not necessarily have to have a causal relationship with study treatment.

    Measured: Up to approximately 2 years 11 months

  3. Best Overall 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 who achieved 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.

    Measured: Up to 2 years

  4. Clinical Benefit Rate (CBR)

    CBR was defined as the number of participants that achieved a CR, PR or stable disease (SD) (SD for at least 6 weeks) as assessed by investigators according to the RECIST v1.1. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as at >=30% decrease under baseline of the sum of diameters of all target lesions. SD was defined as steady state of disease with neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).

    Measured: Up to 2 years

  5. Progression-free Survival (PFS)

    PFS was defined as the time between the day of first treatment and the first documentation of progressive disease or death. Progression was defined as a 20% increase in the sum of the longest diameter of target lesions, the appearance of new lesions and increase of at least 5 mm in the sum of diameters of target lesions. Participants who were withdrawn from the study without documented progression were to be censored at the date of the last known tumor assessment when the participant was known to be progression free. Median PFS was estimated using Kaplan-Meier method and 95% CI for median was computed using the Brookmeyer and Crowley method.

    Measured: Randomization date of first subject until disease progression or death or which ever occur first (2 years)

  6. Overall Survival (OS)

    Overall survival was defined as the time between the date of first treatment to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis were censored at the date of their last being known alive. Median overall survival was estimated using Kaplan-Meier method and 95% CI for median was computed using the Brookmeyer and Crowley method.

    Measured: Randomization date of first subject until death (2 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jan 2012 (estimated)
  2. Study startJan 2013
  3. Primary completionDec 2015
  4. Study completionDec 2015

Why it stopped: Study was terminated due to low enrollment.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01519323
Sponsor's protocol ID
NO25390
Other IDs
2011-000874-67
Status last verified
Aug 2016
First submitted
16 Jan 2012
Last updated
10 Oct 2016
Data monitoring committee
Yes

Publications

  • Chisholm JC, Suvada J, Dunkel IJ, Casanova M, Zhang W, Ritchie N, Choi Y, Park J, Das Thakur M, Simko S, Wan Rachel Tam N, Ferrari A. BRIM-P: A phase I, open-label, multicenter, dose-escalation study of vemurafenib in pediatric patients with surgically incurable, BRAF mutation-positive melanoma. Pediatr Blood Cancer. 2018 May;65(5):e26947. doi: 10.1002/pbc.26947. Epub 2018 Jan 19.

    PubMed 29350463

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing vemurafenib in people with Malignant Melanoma, run by Hoffmann-La Roche at 26 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, Germany, Italy, Australia, France and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD)/Recommended Dose (time frame: Up to 28 days of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01519323, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2016.

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