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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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Country [38] 0 0
Greece
State/province [38] 0 0
Athens
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Greece
State/province [39] 0 0
N. Faliro
Country [40] 0 0
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
Country [49] 0 0
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
State/province [51] 0 0
Stavropol
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Spain
State/province [52] 0 0
Barcelona
Country [53] 0 0
Spain
State/province [53] 0 0
Madrid
Country [54] 0 0
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
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Edgbaston, Birmingham
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Leeds
Country [72] 0 0
United Kingdom
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London
Country [73] 0 0
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.