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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01584648




Registration number
NCT01584648
Ethics application status
Date submitted
23/04/2012
Date registered
25/04/2012
Date last updated
17/02/2021

Titles & IDs
Public title
A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma
Scientific title
A Phase III, Randomized, Double-blinded Study Comparing the Combination of the BRAF Inhibitor, Dabrafenib and the MEK Inhibitor, Trametinib to Dabrafenib and Placebo as First-line Therapy in Subjects With Unresectable (Stage IIIC) or Metastatic (Stage IV) BRAF V600E/K Mutation-positive Cutaneous Melanoma
Secondary ID [1] 0 0
2011-006087-49
Secondary ID [2] 0 0
115306
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dabrafenib
Treatment: Drugs - Trametinib
Treatment: Drugs - Trametinib placebo

Experimental: Dabrafenib + Trametinib - Dabrafenib and Trametinib combination

Active comparator: Dabrafenib + Placebo - Dabrafenib and Trametinib placebo


Treatment: Drugs: Dabrafenib
Dabrafenib 150 mg twice daily

Treatment: Drugs: Trametinib
Trametinib 2 mg once daily

Treatment: Drugs: Trametinib placebo
Dabrafenib 150 mg twice daily and trametinib placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) as Assessed by the Investigator
Timepoint [1] 0 0
From randomization until the earliest date of disease progression (PD) or death due to any cause (up to approximately 6 years)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From the date of randomization until date of death due to any cause (up to approximately 6 years)
Secondary outcome [2] 0 0
Objective Response Rate (ORR) as Assessed by the Investigator
Timepoint [2] 0 0
From randomization until the first documented complete response or partial response (up to approximately 6 years)
Secondary outcome [3] 0 0
Duration of Response (DoR)
Timepoint [3] 0 0
From the time of the first documented response (CR or PR) until disease progression (up to approximately 6 years)
Secondary outcome [4] 0 0
Trametinib Pharmacokinetic Concentrations
Timepoint [4] 0 0
Week 8 (0, 1-3, 4-6 hours post dose), Weeks 16 and 24 (0 hour pre-dose)
Secondary outcome [5] 0 0
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations
Timepoint [5] 0 0
Week 8 (0, 1-3, 4-6 hours post dose), Weeks 16 and 24 (0 hour pre-dose)
Secondary outcome [6] 0 0
Number of Participants With Adverse Events and Serious Adverse Events
Timepoint [6] 0 0
From the time the first dose of study treatment administered until 30 days after discontinuation of study treatment (up to approximately 6 years).

Eligibility
Key inclusion criteria
* Histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV (metastatic), and determined to be BRAF V600E/K mutation-positive using the bioMerieux (bMx) investigational use only (IUO) THxID BRAF Assay (IDE: G120011). The assay will be conducted by a central reference laboratory. Subjects with ocular or mucosal melanoma are not eligible.
* The subject must have a radiologically measurable tumor
* The subject is able to carry out daily life activities without significant difficulty (ECOG performance status score of 0 or 1).
* Able to swallow and retain oral medication
* Sexually active subjects must use acceptable methods of contraception during the course of the study
* Adequate organ system function and blood counts
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment with a BRAF or a MEK inhibitor
* Prior systemic anti-cancer treatment for Stage IIIC (unresectable) or Stage IV (metastatic) melanoma. Prior systemic treatment in the adjuvant setting is allowed. (Note: Ipilimumab treatment must end at least 8 weeks prior to randomization.)
* The subject has received major surgery or certain tyes of cancer therapy with 21 days of starting treatment
* Current use of prohibited medication listed in the protocol
* Left ventricular ejection fraction less than the lower limit of normal
* Uncontrolled blood pressurl
* History or current evidence of retinal vein occlusion or central serous retinopathy
* Brain metastases unless previously treated with surgery or stereotactic radiosurgery and the disease has been stable for at least 12 weeks
* The subject is pregnant or nursing

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/05/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/02/2019
Sample size
Target
Accrual to date
Final
423
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - North Sydney
Recruitment hospital [2] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [3] 0 0
Novartis Investigative Site - Woolloongabba
Recruitment hospital [4] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [5] 0 0
Novartis Investigative Site - Heidelberg
Recruitment hospital [6] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2060 - North Sydney
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia
Country [14] 0 0
Argentina
State/province [14] 0 0
Buenos Aires
Country [15] 0 0
Canada
State/province [15] 0 0
Alberta
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
France
State/province [18] 0 0
Bordeaux
Country [19] 0 0
France
State/province [19] 0 0
Boulogne-Billancourt
Country [20] 0 0
France
State/province [20] 0 0
Lyon Cedex 08
Country [21] 0 0
France
State/province [21] 0 0
Marseille cedex 5
Country [22] 0 0
France
State/province [22] 0 0
Paris Cedex 10
Country [23] 0 0
France
State/province [23] 0 0
Paris
Country [24] 0 0
France
State/province [24] 0 0
Toulouse Cedex
Country [25] 0 0
France
State/province [25] 0 0
Vandoeuvre les Nancy
Country [26] 0 0
Germany
State/province [26] 0 0
Baden-Wuerttemberg
Country [27] 0 0
Germany
State/province [27] 0 0
Bayern
Country [28] 0 0
Germany
State/province [28] 0 0
Hessen
Country [29] 0 0
Germany
State/province [29] 0 0
Niedersachsen
Country [30] 0 0
Germany
State/province [30] 0 0
Nordrhein-Westfalen
Country [31] 0 0
Germany
State/province [31] 0 0
Rheinland-Pfalz
Country [32] 0 0
Germany
State/province [32] 0 0
Saarland
Country [33] 0 0
Germany
State/province [33] 0 0
Sachsen-Anhalt
Country [34] 0 0
Germany
State/province [34] 0 0
Sachsen
Country [35] 0 0
Germany
State/province [35] 0 0
Schleswig-Holstein
Country [36] 0 0
Germany
State/province [36] 0 0
Thueringen
Country [37] 0 0
Germany
State/province [37] 0 0
Berlin
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Greece
State/province [38] 0 0
Athens
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Greece
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N. Faliro
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Greece
State/province [40] 0 0
Thessaloniki
Country [41] 0 0
Italy
State/province [41] 0 0
Lazio
Country [42] 0 0
Italy
State/province [42] 0 0
Liguria
Country [43] 0 0
Italy
State/province [43] 0 0
Lombardia
Country [44] 0 0
Italy
State/province [44] 0 0
Piemonte
Country [45] 0 0
Italy
State/province [45] 0 0
Veneto
Country [46] 0 0
Netherlands
State/province [46] 0 0
Amsterdam
Country [47] 0 0
Netherlands
State/province [47] 0 0
Zwolle
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Kazan
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Russian Federation
State/province [49] 0 0
Moscow
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Russian Federation
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St. Petersburg
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Russian Federation
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Stavropol
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Spain
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Barcelona
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Spain
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Madrid
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Spain
State/province [54] 0 0
Pamplona
Country [55] 0 0
Spain
State/province [55] 0 0
Valencia
Country [56] 0 0
Sweden
State/province [56] 0 0
Goteborg
Country [57] 0 0
Sweden
State/province [57] 0 0
Lund
Country [58] 0 0
Sweden
State/province [58] 0 0
Stockholm
Country [59] 0 0
Sweden
State/province [59] 0 0
Uppsala
Country [60] 0 0
Ukraine
State/province [60] 0 0
Dnipropetrovsk
Country [61] 0 0
Ukraine
State/province [61] 0 0
Donetsk
Country [62] 0 0
Ukraine
State/province [62] 0 0
Khmelnytskyi
Country [63] 0 0
Ukraine
State/province [63] 0 0
Kyiv
Country [64] 0 0
Ukraine
State/province [64] 0 0
Lviv
Country [65] 0 0
Ukraine
State/province [65] 0 0
Sumy
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Middlesex
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Surrey
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Aberdeen
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Bebington
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United Kingdom
State/province [70] 0 0
Edgbaston, Birmingham
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Leeds
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United Kingdom
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London
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United Kingdom
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Newcastle upon Tyne
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United Kingdom
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Nottingham
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Oxford
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Preston

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01584648