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Melanoma and Brain MetastasesPhase 2NCT02039947

Study to Evaluate Treatment of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain

A Phase 2 study testing Dabrafenib and Trametinib in people with Melanoma and Brain Metastases, run by Novartis Pharmaceuticals at 47 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a multi-cohort, open label, Phase II study with Dabrafenib (GSK2118436) and Trametinib (GSK1120212) combination therapy in subject with BRAF mutation-positive melanoma that has metastasized to the brain. This study will evaluate the safety and efficacy of 4 cohorts. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma and Brain Metastases
What is being tested?
Dabrafenib and Trametinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
127 participants
Where
47 sitesin 7 countries
Study dates
21 Feb 2014to 14 Feb 2018
Phase
Phase 2
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ECOG Performance Status range of 0-2
  • Histologically confirmed cutaneous metastatic melanoma of V600 E, K, D or R.
  • May be systemic naïve or received up to two previous systemic treatment regimens for metastatic melanoma.
  • Must be able to undergo MRI and have at least one measurable intracranial lesion for which specific criteria have to be met.

Who cannot join

  • Prior treatment with any BRAF inhibitor or any mitogen-activated protein/extracellular signal-regulated kinase inhibitor.
  • Anti-cancer therapy or investigational anti-cancer therapy or chemotherapy without delayed toxicity within treatment specific timeframe.
  • Treatment with stereotactic radiosurgery or treatment with whole-brain radiation within treatment specific timeframe.
  • Any presence of leptomeningeal disease or any parenchymal brain metastasis
  • History of another malignancy, some exceptions may apply.
  • A history or evidence of cardiovascular risk- specific criteria have to be met
  • A history or current evidence/risk of retinal vein occlusion or retinal pigment epithelial detachment - specific criteria have to be met.

Trial locations and contacts

47 sites in 7 countries.

47 sites in 7 countries

United States11 sites

  • Novartis Investigative Site

    Atlanta, Georgia, 30322

  • Novartis Investigative Site

    Atlanta, Georgia, 30341

  • Novartis Investigative Site

    Aurora, Colorado, 80045

  • Novartis Investigative Site

    Birmingham, Alabama, 35243

  • Novartis Investigative Site

    Boston, Massachusetts, 02215

  • Novartis Investigative Site

    Chapel Hill, North Carolina, 27599

  • Novartis Investigative Site

    Columbus, Ohio, 43210

  • Novartis Investigative Site

    Houston, Texas, 77030

  • Novartis Investigative Site

    Nashville, Tennessee, 37232

  • Novartis Investigative Site

    Pittsburgh, Pennsylvania, 15232

  • Novartis Investigative Site

    San Francisco, California, 94115

Other trials in United States

France11 sites

  • Novartis Investigative Site

    Boulogne-Billancourt, 92100

  • Novartis Investigative Site

    Lille, 59037

  • Novartis Investigative Site

    Marseille, 13385

  • Novartis Investigative Site

    Montpellier, 34295

  • Novartis Investigative Site

    Nantes, 44093

  • Novartis Investigative Site

    Paris, 75475

  • Novartis Investigative Site

    Pierre-Bénite, 69495

  • Novartis Investigative Site

    Poitiers, 86021

  • Novartis Investigative Site

    Rennes, 35042

  • Novartis Investigative Site

    Toulouse, 31052

  • Novartis Investigative Site

    Villejuif, 94805

Other trials in France

Spain8 sites

  • Novartis Investigative Site

    Barcelona, 08036

  • Novartis Investigative Site

    Las Palmas de Gran Canaria, 35016

  • Novartis Investigative Site

    Madrid, 28007

  • Novartis Investigative Site

    Málaga, 29010

  • Novartis Investigative Site

    Palma de Mallorca, 07198

  • Novartis Investigative Site

    Pamplona, 31008

  • Novartis Investigative Site

    Valencia, 46009

  • Novartis Investigative Site

    Zaragoza, 50009

Other trials in Spain

Germany7 sites

  • Novartis Investigative Site

    Cologne, North Rhine-Westphalia, 50937

  • Novartis Investigative Site

    Gera, Thuringia, 07548

  • Novartis Investigative Site

    Hanover, Lower Saxony, 30449

  • Novartis Investigative Site

    Heidelberg, Baden-Wurttemberg, 69120

  • Novartis Investigative Site

    Kiel, Schleswig-Holstein, 24105

  • Novartis Investigative Site

    Munich, Bavaria, 80337

  • Novartis Investigative Site

    Tübingen, Baden-Wurttemberg, 72076

Other trials in Germany

Canada4 sites

  • Novartis Investigative Site

    Edmonton, Alberta, T6G 1Z2

  • Novartis Investigative Site

    Hamilton, Ontario, L8V 5C2

  • Novartis Investigative Site

    Montreal, Quebec, H2W 1S6

  • Novartis Investigative Site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Australia3 sites

  • Novartis Investigative Site

    Greenslopes, Queensland, 4120

  • Novartis Investigative Site

    Melbourne, Victoria, 3004

  • Novartis Investigative Site

    North Sydney, New South Wales, 2060

Other trials in Australia

Italy3 sites

  • Novartis Investigative Site

    Milan, Lombardy, 20133

  • Novartis Investigative Site

    Milan, Lombardy, 20141

  • Novartis Investigative Site

    Padova, Veneto, 35128

Other trials in Italy

About this study

Official title: BRF117277: A Phase II, Open-Label, Multicentre Study of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain

This is a multi-cohort, open label, Phase II study with Dabrafenib (GSK2118436) and Trametinib (GSK1120212) combination therapy in subject with BRAF mutation-positive melanoma that has metastasized to the brain. This study will evaluate the safety and efficacy of 4 cohorts. Cohorts will consist of; V600 E, D, K, R mutations, metastases to the brain, symptomatic and asymptomatic, with or without prior local (brain) therapy, with or without prior local (brain) therapy, and range of ECOG scores from 0-2.

Being tested
Dabrafenib, Trametinib
Keywords
BRAF V600K mutation, Metastatic Melanoma, BRAF V600R mutation, BRAF V600D mutation, BRAF V600E mutation, Brain metastases BRAF inhibitor, Intracranial
Medical subject headings
Melanoma, Brain Neoplasms

What participants receive

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

  • DabrafenibDrug

    Dabrafenib will be provided as 50 mg and 75 mg capsules

  • TrametinibDrug

    Trametinib will be provided as 0.5 mg and 2.0 mg tablets

Study groups in NCT02039947
Study groupRoleWhat they receive
Cohort AExperimentalSubjects will receive dabrafenib 150 milligram (mg) twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity.
Receives: Drug: Dabrafenib; Drug: Trametinib
Cohort BExperimentalSubjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity
Receives: Drug: Dabrafenib; Drug: Trametinib
Cohort CExperimentalSubjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity
Receives: Drug: Dabrafenib; Drug: Trametinib
Cohort DExperimentalSubjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity
Receives: Drug: Dabrafenib; Drug: Trametinib

What is being measured

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

  1. Intracranial Response (IR) Rate in Cohort A

    The intracranial response rate is defined as the percentage of subjects achieving a confirmed intracranial CR or PR. This is based on investigator-assessed best intracranial response.

    Measured: From the start of treatment until disease progression or the start of new anti-cancer therapy

Secondary outcomes (7)

  1. Intracranial Response Rate of Cohorts B, C and D

    The intracranial response rate is defined as the percentage of subjects achieving a confirmed intracranial CR or PR. This is based on investigator-assessed best intracranial response. No hypothesis testing completed for cohort A, B,C and D

    Measured: Approximately 2 years

  2. Disease Control for Intracranial, Extracranial and Overall Response for Each Cohort

    Disease Control rate is defined as the percentage of subjects achieving a confirmed intracranial/extracranial/overall CR or PR or SD or Non-CR/Non-PD. This is based on investigator-assessed response. No hypothesis testing completed for cohort A, B,C and D

    Measured: Approximately 2 years

  3. Extracranial Response Rate (ER) for Each Cohort

    Extracranial Response Rate was defined as the percentage of participants with Complete response (CR) or Partial response (PR) at anytime. This is based on investigator-assessed response. No hypothesis testing completed for cohort A,B,C and D

    Measured: Approximately 2 years

  4. Overall Response (OR) for Each Cohort

    the number of subjects with a confirmed overall Complete response (CR) or Partial response (PR) by investigator assessment using the Response evaluation criteria in solid tumors (RECIST 1.1 criteria). To determine the overall response, all target and non-target lesions will be assessed using modified RECIST 1.1 criteria.

    Measured: Approximately 2 years

  5. Duration of Intracranial, Extracranial and Overall Response for Each Cohort

    Duration of intracranial, extracranial and overall response, are defined as the time from first documented evidence of CR or PR until time of first documented intracranial, extracranial, or overall disease progression. No hypothesis testing completed for cohort A,B,C and D

    Measured: From first documented evidence of CR or PR until time of first documented intracranial, extracranial, or overall disease progression

  6. Progression-free Survival (PFS) for Each Cohort Based on Investigator Assessment

    PFS is defined as the interval between first dose and the earliest date of disease progression or death due to any cause. No hypothesis testing completed for cohort A,B,C and D

    Measured: From the first dose to the earliest date of disease progression or death

  7. Overall Survival (OS) for Each Cohort

    Overall survival (OS) is defined as the time from the first dose until death due to any cause. No hypothesis testing completed for cohort A,B,C and D

    Measured: From the first dose to death

Timeline

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

  1. First posted20 Jan 2014 (estimated)
  2. Study start21 Feb 2014
  3. Primary completion12 May 2017
  4. Study completion14 Feb 2018

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Masking
None (open label)
Enrolment
127 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02039947
Sponsor's protocol ID
117277
Status last verified
May 2019
First submitted
19 Dec 2013
Last updated
21 May 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Syeda MM, Wiggins JM, Corless BC, Long GV, Flaherty KT, Schadendorf D, Nathan PD, Robert C, Ribas A, Davies MA, Grob JJ, Gasal E, Squires M, Marker M, Garrett J, Brase JC, Polsky D. Circulating tumour DNA in patients with advanced melanoma treated with dabrafenib or dabrafenib plus trametinib: a clinical validation study. Lancet Oncol. 2021 Mar;22(3):370-380. doi: 10.1016/S1470-2045(20)30726-9. Epub 2021 Feb 12.

    PubMed 33587894

  • Davies MA, Saiag P, Robert C, Grob JJ, Flaherty KT, Arance A, Chiarion-Sileni V, Thomas L, Lesimple T, Mortier L, Moschos SJ, Hogg D, Marquez-Rodas I, Del Vecchio M, Lebbe C, Meyer N, Zhang Y, Huang Y, Mookerjee B, Long GV. Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol. 2017 Jul;18(7):863-873. doi: 10.1016/S1470-2045(17)30429-1. Epub 2017 Jun 4.

    PubMed 28592387

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dabrafenib and Trametinib in people with Melanoma and Brain Metastases, run by Novartis Pharmaceuticals at 47 sites in 7 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 4 inclusion and 7 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: finished, as of the sponsor's last update on 21 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 47 sites in United States, France, Spain, Germany, Canada and 2 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 21 May 2019). 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?

Intracranial Response (IR) Rate in Cohort A (time frame: From the start of treatment until disease progression or the start of new anti-cancer therapy). 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 NCT02039947, which also lists 2 linked publications.

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 21 May 2019.

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