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A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma

Primary Purpose

Melanoma

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Dabrafenib

Trametinib

Trametinib placebo

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Randomized study, combination therapy, BRAF inhibitor, GSK1120212, BRAF V600E/K mutation-positive cutaneous melanoma, trametinib, GSK2118436, MEK inhibitor, Phase III, dabrafenib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Dabrafenib + Trametinib

Dabrafenib + Placebo

Arm Description

Dabrafenib and Trametinib combination

Dabrafenib and Trametinib placebo

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS) as Assessed by the Investigator

PFS is defined as the interval between the date of randomization and the earliest date of PD or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the investigator according to RECIST, version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. In addition, the sum must have an absolute increase from nadir of 5 mm. The appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation, was also included as PD. Participants who received anti-cancer therapy prior to the date of documented events, were censored at the last adequate assessment prior to the initiation of therapy. If the participant did not have documented progression or death, PFS was censored at the date of the last adequate assessment.

Secondary Outcome Measures

Overall Survival (OS)

OS is defined as the interval of time between the date of randomization and the date of death due to any cause. For the participants who did not die, overall survival was censored at the date of last contact.

Objective Response Rate (ORR) as Assessed by the Investigator

ORR is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR). A participant was defined as a responder if he/she sustained a complete response (CR: the disappearance of all target lesions and any pathological lymph nodes must have a short axis of <10 mm and the disappearance of all non-target lesions) or partial response (PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm). Only descriptive analysis performed.

Duration of Response (DoR)

Duration of response is defined as the time from the first documented complete response (CR: the disappearance of all target lesions and any pathological lymph nodes must have a short axis of <10 mm and the disappearance of all non-target lesions) or partial response (PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm) until disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5mm or the appearance of one or more new lesions, or the worsening of non target lesions significant enough to require study treatment discontinuation. PD was based on the radiological evidence by investigator. Only descriptive analysis performed.

Trametinib Pharmacokinetic Concentrations

Blood samples were collected for Pharmacokinetic (PK) analysis in all participants. Three blood samples were collected at Week 8: pre-dose, 1-3 hours post dose, and 4-6 hours post dose. One pre-dose blood sample was obtained at Weeks 16 and 24. Only descriptive analysis performed.

Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations

Blood samples were collected for PK analysis in all participants. Three blood samples were collected at Week 8: pre-dose, 1-3 hours post dose, and 4-6 hours post dose. One pre-dose blood sample was obtained at Weeks 16 and 24. Plasma concentrations of Dabrafenib (GSK2118436) and its metabolites (Hydroxy-Dabrafenib (GSK2285403), Carboxy-Dabrafenib (GSK2298683), and Desmethyl-Dabrafenib (GSK2167542)) were determined using the currently approved analytical methodology. Only descriptive analysis performed.

Number of Participants With Adverse Events and Serious Adverse Events

Analysis of absolute and relative frequencies for Adverse Event (AE) and Serious Adverse Event (SAE) by primary System Organ Class (SOC) to characterize the safety of dabrafenib and trametinib combination therapy through the monitoring of relevant clinical and laboratory safety parameters. In addition, new malignancies and AEs possibly related to study treatment were collected even if they occurred more than 30 days post-treatment. Only descriptive analysis performed.

Full Information

NCT ID

NCT01584648

First Posted

April 23, 2012

Last Updated

February 8, 2021

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01584648

Brief Title

A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma

Official 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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Completed

Study Start Date

May 4, 2012 (Actual)

Primary Completion Date

August 26, 2013 (Actual)

Study Completion Date

February 28, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This was a two-arm, double-blinded, randomized, Phase III study comparing dabrafenib and trametinib combination therapy to dabrafenib administered with a placebo (dabrafenib monotherapy). Subjects with histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV, and BRAF V600E/K mutation positive were screened for eligibility. Subjects who had prior systemic anti-cancer treatment in the advanced or metastatic setting were not eligible although prior systemic treatment in the adjuvant setting was allowed. Subjects were stratified according to the baseline lactate dehydrogenase level and BRAF genotype.

Detailed Description

Dabrafenib and trametinib was administered orally at their recommended monotherapy doses of 150 mg b.i.d and 2 mg q.d., respectively. Subjects in the combination therapy arm received both agents; subjects in the dabrafenib monotherapy arm received dabrafenib and placebo. Treatment was continued in both arms until disease progression, death, unacceptable toxicity, or withdrawal of consent. After treatment discontinuation, subjects were followed for survival and disease progression as applicable to collect data for the secondary objective of overall survival (OS). Crossover to the combination therapy arm was allowed for subjects still receiving study treatment on the dabrafenib monotherapy arm after the positive result for the final OS analysis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma

Keywords

Randomized study, combination therapy, BRAF inhibitor, GSK1120212, BRAF V600E/K mutation-positive cutaneous melanoma, trametinib, GSK2118436, MEK inhibitor, Phase III, dabrafenib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

423 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dabrafenib + Trametinib

Arm Type

Experimental

Arm Description

Dabrafenib and Trametinib combination

Arm Title

Dabrafenib + Placebo

Arm Type

Active Comparator

Arm Description

Dabrafenib and Trametinib placebo

Intervention Type

Drug

Intervention Name(s)

Dabrafenib

Other Intervention Name(s)

GSK2118436

Intervention Description

Dabrafenib 150 mg twice daily

Intervention Type

Drug

Intervention Name(s)

Trametinib

Other Intervention Name(s)

GSK1120212

Intervention Description

Trametinib 2 mg once daily

Intervention Type

Drug

Intervention Name(s)

Trametinib placebo

Other Intervention Name(s)

Placebo

Intervention Description

Dabrafenib 150 mg twice daily and trametinib placebo

Primary Outcome Measure Information:

Title

Progression-Free Survival (PFS) as Assessed by the Investigator

Description

Time Frame

From randomization until the earliest date of disease progression (PD) or death due to any cause (up to approximately 6 years)

Secondary Outcome Measure Information:

Title

Overall Survival (OS)

Description

Time Frame

From the date of randomization until date of death due to any cause (up to approximately 6 years)

Title

Objective Response Rate (ORR) as Assessed by the Investigator

Description

Time Frame

From randomization until the first documented complete response or partial response (up to approximately 6 years)

Title

Duration of Response (DoR)

Description

Time Frame

From the time of the first documented response (CR or PR) until disease progression (up to approximately 6 years)

Title

Trametinib Pharmacokinetic Concentrations

Description

Time Frame

Week 8 (0, 1-3, 4-6 hours post dose), Weeks 16 and 24 (0 hour pre-dose)

Title

Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations

Description

Time Frame

Week 8 (0, 1-3, 4-6 hours post dose), Weeks 16 and 24 (0 hour pre-dose)

Title

Number of Participants With Adverse Events and Serious Adverse Events

Description

Time Frame

From the time the first dose of study treatment administered until 30 days after discontinuation of study treatment (up to approximately 6 years).

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85258

Country

United States

Facility Name

Novartis Investigative Site

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85719

Country

United States

Facility Name

Novartis Investigative Site

City

Los Angeles

State/Province

California

ZIP/Postal Code

90024

Country

United States

Facility Name

Novartis Investigative Site

City

Fort Myers

State/Province

Florida

ZIP/Postal Code

33916

Country

United States

Facility Name

Novartis Investigative Site

City

Saint Petersburg

State/Province

Florida

ZIP/Postal Code

33705

Country

United States

Facility Name

Novartis Investigative Site

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Facility Name

Novartis Investigative Site

City

West Palm Beach

State/Province

Florida

ZIP/Postal Code

33401

Country

United States

Facility Name

Novartis Investigative Site

City

Peoria

State/Province

Illinois

ZIP/Postal Code

61615-7822

Country

United States

Facility Name

Novartis Investigative Site

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Novartis Investigative Site

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Novartis Investigative Site

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

Novartis Investigative Site

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Novartis Investigative Site

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45242

Country

United States

Facility Name

Novartis Investigative Site

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Novartis Investigative Site

City

Columbia

State/Province

South Carolina

ZIP/Postal Code

29210

Country

United States

Facility Name

Novartis Investigative Site

City

Chattanooga

State/Province

Tennessee

ZIP/Postal Code

37404

Country

United States

Facility Name

Novartis Investigative Site

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

Novartis Investigative Site

City

Fort Worth

State/Province

Texas

ZIP/Postal Code

76104

Country

United States

Facility Name

Novartis Investigative Site

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23230

Country

United States

Facility Name

Novartis Investigative Site

City

Caba

State/Province

Buenos Aires

ZIP/Postal Code

C1425DTG

Country

Argentina

Facility Name

Novartis Investigative Site

City

Capital Federal

State/Province

Buenos Aires

ZIP/Postal Code

C1426ANZ

Country

Argentina

Facility Name

Novartis Investigative Site

City

Ciudad Autonoma de Buenos Aires

State/Province

Buenos Aires

ZIP/Postal Code

C1050AAK

Country

Argentina

Facility Name

Novartis Investigative Site

City

North Sydney

State/Province

New South Wales

ZIP/Postal Code

2060

Country

Australia

Facility Name

Novartis Investigative Site

City

Westmead

State/Province

New South Wales

ZIP/Postal Code

2145

Country

Australia

Facility Name

Novartis Investigative Site

City

Woolloongabba

State/Province

Queensland

ZIP/Postal Code

4102

Country

Australia

Facility Name

Novartis Investigative Site

City

Adelaide

State/Province

South Australia

ZIP/Postal Code

5000

Country

Australia

Facility Name

Novartis Investigative Site

City

Heidelberg

State/Province

Victoria

ZIP/Postal Code

3084

Country

Australia

Facility Name

Novartis Investigative Site

City

Nedlands

State/Province

Western Australia

ZIP/Postal Code

6009

Country

Australia

Facility Name

Novartis Investigative Site

City

Edmonton

State/Province

Alberta

ZIP/Postal Code

T6G 1Z2

Country

Canada

Facility Name

Novartis Investigative Site

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L8V 5C2

Country

Canada

Facility Name

Novartis Investigative Site

City

London

State/Province

Ontario

ZIP/Postal Code

N6A 4L6

Country

Canada

Facility Name

Novartis Investigative Site

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2M9

Country

Canada

Facility Name

Novartis Investigative Site

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H2W 1S6

Country

Canada

Facility Name

Novartis Investigative Site

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H3A 1A1

Country

Canada

Facility Name

Novartis Investigative Site

City

Bordeaux

ZIP/Postal Code

33075

Country

France

Facility Name

Novartis Investigative Site

City

Boulogne-Billancourt

ZIP/Postal Code

92100

Country

France

Facility Name

Novartis Investigative Site

City

Lyon Cedex 08

ZIP/Postal Code

69373

Country

France

Facility Name

Novartis Investigative Site

City

Marseille cedex 5

ZIP/Postal Code

13385

Country

France

Facility Name

Novartis Investigative Site

City

Paris Cedex 10

ZIP/Postal Code

75475

Country

France

Facility Name

Novartis Investigative Site

City

Paris

ZIP/Postal Code

75006

Country

France

Facility Name

Novartis Investigative Site

City

Paris

ZIP/Postal Code

75018

Country

France

Facility Name

Novartis Investigative Site

City

Toulouse Cedex

ZIP/Postal Code

31052

Country

France

Facility Name

Novartis Investigative Site

City

Vandoeuvre les Nancy

ZIP/Postal Code

54511

Country

France

Facility Name

Novartis Investigative Site

City

Heidelberg

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

69120

Country

Germany

Facility Name

Novartis Investigative Site

City

Heilbronn

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

74078

Country

Germany

Facility Name

Novartis Investigative Site

City

Mannheim

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

68167

Country

Germany

Facility Name

Novartis Investigative Site

City

Tuebingen

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

72076

Country

Germany

Facility Name

Novartis Investigative Site

City

Ulm

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

89081

Country

Germany

Facility Name

Novartis Investigative Site

City

Augsburg

State/Province

Bayern

ZIP/Postal Code

86179

Country

Germany

Facility Name

Novartis Investigative Site

City

Erlangen

State/Province

Bayern

ZIP/Postal Code

91054

Country

Germany

Facility Name

Novartis Investigative Site

City

Muenchen

State/Province

Bayern

ZIP/Postal Code

80337

Country

Germany

Facility Name

Novartis Investigative Site

City

Muenchen

State/Province

Bayern

ZIP/Postal Code

80804

Country

Germany

Facility Name

Novartis Investigative Site

City

Muenchen

State/Province

Bayern

ZIP/Postal Code

81675

Country

Germany

Facility Name

Novartis Investigative Site

City

Nuernberg

State/Province

Bayern

ZIP/Postal Code

90419

Country

Germany

Facility Name

Novartis Investigative Site

City

Regensburg

State/Province

Bayern

ZIP/Postal Code

93053

Country

Germany

Facility Name

Novartis Investigative Site

City

Wuerzburg

State/Province

Bayern

ZIP/Postal Code

97080

Country

Germany

Facility Name

Novartis Investigative Site

City

Darmstadt

State/Province

Hessen

ZIP/Postal Code

64283

Country

Germany

Facility Name

Novartis Investigative Site

City

Marburg

State/Province

Hessen

ZIP/Postal Code

35033

Country

Germany

Facility Name

Novartis Investigative Site

City

Buxtehude

State/Province

Niedersachsen

ZIP/Postal Code

21614

Country

Germany

Facility Name

Novartis Investigative Site

City

Hannover

State/Province

Niedersachsen

ZIP/Postal Code

30625

Country

Germany

Facility Name

Novartis Investigative Site

City

Bonn

State/Province

Nordrhein-Westfalen

ZIP/Postal Code

53127

Country

Germany

Facility Name

Novartis Investigative Site

City

Essen

State/Province

Nordrhein-Westfalen

ZIP/Postal Code

45122

Country

Germany

Facility Name

Novartis Investigative Site

City

Koeln

State/Province

Nordrhein-Westfalen

ZIP/Postal Code

50937

Country

Germany

Facility Name

Novartis Investigative Site

City

Mainz

State/Province

Rheinland-Pfalz

ZIP/Postal Code

55131

Country

Germany

Facility Name

Novartis Investigative Site

City

Homburg

State/Province

Saarland

ZIP/Postal Code

66421

Country

Germany

Facility Name

Novartis Investigative Site

City

Magdeburg

State/Province

Sachsen-Anhalt

ZIP/Postal Code

39120

Country

Germany

Facility Name

Novartis Investigative Site

City

Dresden

State/Province

Sachsen

ZIP/Postal Code

01307

Country

Germany

Facility Name

Novartis Investigative Site

City

Leipzig

State/Province

Sachsen

ZIP/Postal Code

04103

Country

Germany

Facility Name

Novartis Investigative Site

City

Kiel

State/Province

Schleswig-Holstein

ZIP/Postal Code

24105

Country

Germany

Facility Name

Novartis Investigative Site

City

Luebeck

State/Province

Schleswig-Holstein

ZIP/Postal Code

23538

Country

Germany

Facility Name

Novartis Investigative Site

City

Erfurt

State/Province

Thueringen

ZIP/Postal Code

99089

Country

Germany

Facility Name

Novartis Investigative Site

City

Gera

State/Province

Thueringen

ZIP/Postal Code

07548

Country

Germany

Facility Name

Novartis Investigative Site

City

Jena

State/Province

Thueringen

ZIP/Postal Code

07740

Country

Germany

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

10117

Country

Germany

Facility Name

Novartis Investigative Site

City

Athens

ZIP/Postal Code

11527

Country

Greece

Facility Name

Novartis Investigative Site

City

N. Faliro

ZIP/Postal Code

185 47

Country

Greece

Facility Name

Novartis Investigative Site

City

Thessaloniki

ZIP/Postal Code

564 29

Country

Greece

Facility Name

Novartis Investigative Site

City

Roma

State/Province

Lazio

ZIP/Postal Code

00144

Country

Italy

Facility Name

Novartis Investigative Site

City

Roma

State/Province

Lazio

ZIP/Postal Code

00167

Country

Italy

Facility Name

Novartis Investigative Site

City

Genova

State/Province

Liguria

ZIP/Postal Code

16132

Country

Italy

Facility Name

Novartis Investigative Site

City

Bergamo

State/Province

Lombardia

ZIP/Postal Code

24127

Country

Italy

Facility Name

Novartis Investigative Site

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20133

Country

Italy

Facility Name

Novartis Investigative Site

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20141

Country

Italy

Facility Name

Novartis Investigative Site

City

Candiolo (TO)

State/Province

Piemonte

ZIP/Postal Code

10060

Country

Italy

Facility Name

Novartis Investigative Site

City

Padova

State/Province

Veneto

ZIP/Postal Code

35128

Country

Italy

Facility Name

Novartis Investigative Site

City

Amsterdam

ZIP/Postal Code

1066 CX

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Amsterdam

ZIP/Postal Code

1081 HV

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Zwolle

ZIP/Postal Code

8025 AB

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Kazan

ZIP/Postal Code

420029

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

Moscow

ZIP/Postal Code

143423

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

St. Petersburg

ZIP/Postal Code

197758

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

Stavropol

ZIP/Postal Code

355047

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Novartis Investigative Site

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Novartis Investigative Site

City

Madrid

ZIP/Postal Code

28034

Country

Spain

Facility Name

Novartis Investigative Site

City

Madrid

ZIP/Postal Code

28041

Country

Spain

Facility Name

Novartis Investigative Site

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

Novartis Investigative Site

City

Pamplona

ZIP/Postal Code

31008

Country

Spain

Facility Name

Novartis Investigative Site

City

Valencia

ZIP/Postal Code

46010

Country

Spain

Facility Name

Novartis Investigative Site

City

Goteborg

ZIP/Postal Code

SE-413 45

Country

Sweden

Facility Name

Novartis Investigative Site

City

Lund

ZIP/Postal Code

SE-221 85

Country

Sweden

Facility Name

Novartis Investigative Site

City

Stockholm

ZIP/Postal Code

SE-171 76

Country

Sweden

Facility Name

Novartis Investigative Site

City

Uppsala

ZIP/Postal Code

SE-751 85

Country

Sweden

Facility Name

Novartis Investigative Site

City

Dnipropetrovsk

ZIP/Postal Code

49100

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Dnipropetrovsk

ZIP/Postal Code

49102

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Donetsk

ZIP/Postal Code

83092

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Khmelnytskyi

ZIP/Postal Code

29009

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Kyiv

ZIP/Postal Code

03022

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Lviv

ZIP/Postal Code

79031

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Sumy

ZIP/Postal Code

40005

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Northwood

State/Province

Middlesex

ZIP/Postal Code

HA6 2RN

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Sutton

State/Province

Surrey

ZIP/Postal Code

SM2 5PT

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Aberdeen

ZIP/Postal Code

AB25 2ZN

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Bebington

ZIP/Postal Code

CH63 4JY

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Edgbaston, Birmingham

ZIP/Postal Code

B15 2TH

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Leeds

ZIP/Postal Code

LS9 7TF

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

London

ZIP/Postal Code

SW3 6JJ

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Newcastle upon Tyne

ZIP/Postal Code

NE7 7DN

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Nottingham

ZIP/Postal Code

NG5 1PB

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Oxford

ZIP/Postal Code

OX3 7LJ

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Preston

ZIP/Postal Code

PR2 9HT

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

34225229

Citation

Schadendorf D, Robert C, Dummer R, Flaherty KT, Tawbi HA, Menzies AM, Banerjee H, Lau M, Long GV. Pyrexia in patients treated with dabrafenib plus trametinib across clinical trials in BRAF-mutant cancers. Eur J Cancer. 2021 Aug;153:234-241. doi: 10.1016/j.ejca.2021.05.005. Epub 2021 Jul 2.

Results Reference

derived

PubMed Identifier

33587894

Citation

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.

Results Reference

derived

PubMed Identifier

31166680

Citation

Robert C, Grob JJ, Stroyakovskiy D, Karaszewska B, Hauschild A, Levchenko E, Chiarion Sileni V, Schachter J, Garbe C, Bondarenko I, Gogas H, Mandala M, Haanen JBAG, Lebbe C, Mackiewicz A, Rutkowski P, Nathan PD, Ribas A, Davies MA, Flaherty KT, Burgess P, Tan M, Gasal E, Voi M, Schadendorf D, Long GV. Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma. N Engl J Med. 2019 Aug 15;381(7):626-636. doi: 10.1056/NEJMoa1904059. Epub 2019 Jun 4.

Results Reference

derived

PubMed Identifier

27864013

Citation

Long GV, Grob JJ, Nathan P, Ribas A, Robert C, Schadendorf D, Lane SR, Mak C, Legenne P, Flaherty KT, Davies MA. Factors predictive of response, disease progression, and overall survival after dabrafenib and trametinib combination treatment: a pooled analysis of individual patient data from randomised trials. Lancet Oncol. 2016 Dec;17(12):1743-1754. doi: 10.1016/S1470-2045(16)30578-2. Epub 2016 Nov 16.

Results Reference

derived

PubMed Identifier

26037941

Citation

Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Grob JJ, Chiarion-Sileni V, Lebbe C, Mandala M, Millward M, Arance A, Bondarenko I, Haanen JB, Hansson J, Utikal J, Ferraresi V, Kovalenko N, Mohr P, Probachai V, Schadendorf D, Nathan P, Robert C, Ribas A, DeMarini DJ, Irani JG, Swann S, Legos JJ, Jin F, Mookerjee B, Flaherty K. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015 Aug 1;386(9992):444-51. doi: 10.1016/S0140-6736(15)60898-4. Epub 2015 May 31.

Results Reference

derived

PubMed Identifier

25794603

Citation

Schadendorf D, Amonkar MM, Stroyakovskiy D, Levchenko E, Gogas H, de Braud F, Grob JJ, Bondarenko I, Garbe C, Lebbe C, Larkin J, Chiarion-Sileni V, Millward M, Arance A, Mandala M, Flaherty KT, Nathan P, Ribas A, Robert C, Casey M, DeMarini DJ, Irani JG, Aktan G, Long GV. Health-related quality of life impact in a randomised phase III study of the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma. Eur J Cancer. 2015 May;51(7):833-40. doi: 10.1016/j.ejca.2015.03.004. Epub 2015 Mar 17.

Results Reference

derived

PubMed Identifier

25411413

Citation

Menzies AM, Ashworth MT, Swann S, Kefford RF, Flaherty K, Weber J, Infante JR, Kim KB, Gonzalez R, Hamid O, Schuchter L, Cebon J, Sosman JA, Little S, Sun P, Aktan G, Ouellet D, Jin F, Long GV, Daud A. Characteristics of pyrexia in BRAFV600E/K metastatic melanoma patients treated with combined dabrafenib and trametinib in a phase I/II clinical trial. Ann Oncol. 2015 Feb;26(2):415-21. doi: 10.1093/annonc/mdu529. Epub 2014 Nov 18.

Results Reference

derived

PubMed Identifier

25265492

Citation

Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Grob JJ, Chiarion Sileni V, Lebbe C, Mandala M, Millward M, Arance A, Bondarenko I, Haanen JB, Hansson J, Utikal J, Ferraresi V, Kovalenko N, Mohr P, Probachai V, Schadendorf D, Nathan P, Robert C, Ribas A, DeMarini DJ, Irani JG, Casey M, Ouellet D, Martin AM, Le N, Patel K, Flaherty K. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014 Nov 13;371(20):1877-88. doi: 10.1056/NEJMoa1406037. Epub 2014 Sep 29.

Results Reference

derived

Learn more about this trial

A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma

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A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma

Melanoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial