GSK1120212 vs Chemotherapy in Advanced or Metastatic BRAF V600E/K Mutation-positive Melanoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01245062
First received: November 18, 2010
Last updated: October 17, 2013
Last verified: October 2013
  Purpose

This is a two-arm, open-label, randomized Phase III study comparing single agent GSK1120212 to chemotherapy (either dacarbazine or paclitaxel) in subjects with Stage IIIc or Stage IV malignant cutaneous melanoma. All subjects must have a BRAF mutation-positive tumour sample. Subjects who have received up to one prior regimen of chemotherapy in the advanced or metastatic melanoma setting will be enrolled into the study. Subjects with any prior BRAF or MEK inhibitor use will be excluded. Approximately 297 subjects will be enrolled with 2:1 randomization (198 subjects into the GSK1120212 arm and 99 subjects into the chemotherapy arm). The primary endpoint for the statistical analysis will be a comparison of progression free survival for subjects receiving GSK1120212 compared to chemotherapy. Subjects who have progression on chemotherapy will be offered the option to receive GSK1120212.


Condition Intervention Phase
Melanoma
Drug: GSK1120212
Drug: Chemotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Open-label Study Comparing GSK1120212 to Chemotherapy in Subjects With Advanced or Metastatic BRAF V600E/K Mutation-positive Melanoma

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Progression-free Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases as Assessed by the Investigator and Independent Review [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) is defined as the time from randomization to the first documented occurrence of disease progression or death. PFS for investigator-assessed and blinded, independent, central review committee (BRIC)-assessed responses was summarized per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1, which is a set of published rules defining when cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment. Disease progression is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation.


Secondary Outcome Measures:
  • Progression-free Survival in All Participants [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ] [ Designated as safety issue: No ]
    PFS is defined as the time from the date of randomization to the first documented occurrence of PD or death. Investigator-assessed and BRIC-assessed PFS were summarized per RECIST, Version 1.1. 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 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.

  • PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and Without Prior Chemotherapy as Assessed by the Investigator [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ] [ Designated as safety issue: No ]
    PFS is defined as the time from the date of randomization to the first documented occurrence of PD or death. Investigator-assessed PFS was summarized per RECIST, Version 1.1. 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 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.

  • PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and With Prior Chemotherapy as Assessed by the Investigator [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ] [ Designated as safety issue: No ]
    PFS is defined as the time from the date of randomization to the first documented occurrence of PD or death. Investigator-assessed PFS was summarized per RECIST, Version 1.1. 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 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.

  • Overall Survival in All Participants [ Time Frame: Day 1 until death due to any cause (average of 4.8 months) ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from the date of randomization to the date of death due to any cause.

  • Overall Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases [ Time Frame: Day 1 until death due to any cause (average of 4.8 months) ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from the date of randomization to the date of death due to any cause.

  • Number of BRAF V600E Mutation-positive Participants Without a History of Brain Metastases With Overall Response (OR) as Assessed by the Investigator and Independent Review [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ] [ Designated as safety issue: No ]
    OR is defined as the number of participants with evidence of complete response (CR; disappearance of all target lesions. Any pathological lymph node must be less than 10 mm in the short axis) or partial response (PR: at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator and an independent review per RECIST, Version 1.1.

  • Number of Participants With OR as Assessed by the Investigator and Independent Review [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ] [ Designated as safety issue: No ]
    OR is defined as the number of participants with evidence of complete response (CR; disappearance of all target lesions. Any pathological lymph node must be less than 10 mm in the short axis) or partial response (PR: at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator and an independent review per RECIST, Version 1.1.

  • Number of BRAF V600E Mutation-positive Participants Classified as Confirmed Responders (CR and PR) as Assessed by the Investigator [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ] [ Designated as safety issue: No ]
    OR is defined as the number of participants with evidence of complete response (CR; disappearance of all extranodal lesions. Any pathological lymph node must be less than 10 mm in the short axis) or partial response (PR: at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator per RECIST, Version 1.1.

  • Number of BRAF V600K Mutation-positive Participants Classified as Confirmed Responders (CR and PR) as Assessed by the Investigator [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ] [ Designated as safety issue: No ]
    OR is defined as the number of participants with evidence of complete response (CR; disappearance of all extranodal lesions. Any pathological lymph node must be less than 10 mm in the short axis) or partial response (PR: at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator per RECIST, Version 1.1.

  • Number of Participants With OR Following Cross-over to Trametinib [ Time Frame: Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 2.72 months) ] [ Designated as safety issue: No ]
    OR is defined as the number of participants with evidence of CR (disappearance of all target lesions. Any pathological lymph node must be less than 10 millimeters in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator in participants following cross-over to Trametinib. The evaluation was carried out by the Investigator per RECIST, Version 1.1.

  • Duration of Response (DR) for All BRAF V600E Mutation-positive Participants Without a Prior History of Brain Metastases Classifed as Confirmed Responders (CR or PR) as Assessed by the Investigator and Independent Review [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ] [ Designated as safety issue: No ]
    DR is defined as the time from the first documented evidence of CR (disappearance of all target lesions. Any pathological lymph node must be less than 10 mm in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) until PD (at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation) or death due to any cause. DR for the investigator-assessed (INVA) and independently-assessed (INDA) response data were summarized per RECIST, Version 1.1.

  • DR for All Confirmed Responders (CR or PR) as Assessed by the Investigator or Independent Review [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ] [ Designated as safety issue: No ]
    DR is defined as thetime from the first documented evidence of CR (disappearance of all target lesions. Any pathological lymph node must be less than 10 mm in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) until 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 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation. DR for the INVA and INDA response data was summarized per RECIST, Version 1.1.

  • DR for All Responders (CR or PR) Following Cross-over to Trametinib as Assessed by the Investigator [ Time Frame: Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 2.72 months) ] [ Designated as safety issue: No ]
    DR is defined as the time from the first documented evidence of CR (disappearance of all extranodal lesions. Any pathological lymph node must be less than 10 mm in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) until 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 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation. DR data were summarized per RECIST, Version 1.1.

  • PFS Following Cross-over to Trametinib as Assessed by the Investigator [ Time Frame: Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 2.72 months) ] [ Designated as safety issue: No ]
    PFS is defined as the time from the first dose of cross-over therapy to the first documented occurrence of PD or death. PFS was summarized per RECIST, Version 1.1. 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 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.


Enrollment: 322
Study Start Date: November 2010
Estimated Study Completion Date: January 2014
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK1120212
MEK inhibitor
Drug: GSK1120212
MEK inhibitor
Active Comparator: Chemotherapy
Investigator Choice of DTIC or paclitaxel
Drug: Chemotherapy
Investigator Choice of DTIC or paclitaxel
Experimental: Crossover
MEK inhibitor after documented progression on Chemotherapy Arm
Drug: GSK1120212
MEK inhibitor

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥18 years of age
  • Stage III unresectable (Stage IIIc) or metastatic (Stage IV) cutaneous melanoma which is also determined to be BRAF V600E/K mutation-positive by the central laboratory
  • Received no prior treatment or up to one prior regimen of chemotherapy for advanced or metastatic melanoma. Prior treatment with immunotherapy (with the exception of prior ipilimumab, which is only allowed if given in the adjuvant setting), cytokine therapy, biological or vaccine regimen is permitted. Prior use of sorafenib is allowed
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
  • Women of childbearing potential and men with reproductive potential must agree to use effective contraception during the study. Additionally women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomization
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
  • Adequate screening organ function

Exclusion Criteria:

  • Any prior use of BRAF inhibitors or MEK inhibitors.
  • Subjects who have received dacarbazine or paclitaxel prior to randomization will not be eligible to receive the same chemotherapy as study medication (i.e. a subject who received prior dacarbazine cannot receive dacarbazine on this trial and would thus receive paclitaxel if randomized to the control arm)
  • History of another malignancy. Exception: Subjects who have been disease-free for 3 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Subjects with second malignancies that are indolent or definitively treated may be enrolled. Consult GSK Medical Monitor if unsure whether second malignancies meet requirements specified above
  • Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection which will be allowed)
  • Brain metastases with the following exceptions that are ALL confirmed by the GSK Medical Monitor:

All known lesions must be previously treated with surgery or stereotactic radiosurgery, and Brain lesion(s), if still present, must be confirmed stable (i.e. no increase in lesion size) for ≥90 days prior to randomization (must be documented with two consecutive MRI or CT scans using contrast), and asymptomatic with no corticosteroids requirement for ≥ 30 days prior to randomization, and no enzyme-inducing anticonvulsants for ≥ 30 days prior to randomization

  • History or evidence of cardiovascular risk including any of the following:

    • QTcB ≥ 480 msec.
    • History or evidence of current clinically significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation for >30 days prior to randomization are eligible
    • History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization.
    • History or evidence of current ≥ Class II congestive heart failure as defined by New York Heart Association
  • History of interstitial lung disease or pneumonitis
  • History or current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):

    • History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes).
    • Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as:
  • Evidence of new optic disc cupping.
  • Intraocular pressure > 21 mm Hg as measured by tonography
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01245062

  Hide Study Locations
Locations
United States, Arizona
GSK Investigational Site
Tucson, Arizona, United States, 85724-5024
United States, Florida
GSK Investigational Site
Fort Myers, Florida, United States, 33916
United States, Georgia
GSK Investigational Site
Athens, Georgia, United States, 30607
GSK Investigational Site
Marietta, Georgia, United States, 30060
United States, Iowa
GSK Investigational Site
Iowa City, Iowa, United States, 52242
United States, Louisiana
GSK Investigational Site
Metairie, Louisiana, United States, 70006
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02114
United States, New Jersey
GSK Investigational Site
Morristown, New Jersey, United States, 07962-1956
United States, Ohio
GSK Investigational Site
Columbus, Ohio, United States, 43210
United States, South Carolina
GSK Investigational Site
Columbia, South Carolina, United States, 29210
United States, Tennessee
GSK Investigational Site
Chattanooga, Tennessee, United States, 37404
GSK Investigational Site
Memphis, Tennessee, United States, 38120
GSK Investigational Site
Nashville, Tennessee, United States, 37203
Argentina
GSK Investigational Site
Caba, Buenos Aires, Argentina, C1425DTG
Australia, Australian Capital Territory
GSK Investigational Site
Garran, Australian Capital Territory, Australia, 2606
Australia, New South Wales
GSK Investigational Site
Port Macquarie, New South Wales, Australia, 2444
GSK Investigational Site
Waratah, New South Wales, Australia, 2300
Australia, Queensland
GSK Investigational Site
South Brisbane, Queensland, Australia, 4101
GSK Investigational Site
Townsville, Queensland, Australia, 4810
GSK Investigational Site
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
GSK Investigational Site
Kurralta Park, South Australia, Australia, 5037
GSK Investigational Site
Woodville, South Australia, Australia, 5011
Australia, Victoria
GSK Investigational Site
Heidelberg, Victoria, Australia, 3084
GSK Investigational Site
Melbourne, Victoria, Australia, 3004
Austria
GSK Investigational Site
Graz, Austria, 8036
GSK Investigational Site
Wien, Austria, 1090
Belgium
GSK Investigational Site
Brussels, Belgium, 1200
GSK Investigational Site
Charleroi, Belgium, 6000
GSK Investigational Site
Gent, Belgium, 9000
GSK Investigational Site
Jette, Belgium, 1090
GSK Investigational Site
Kortrijk, Belgium, 8500
GSK Investigational Site
Leuven, Belgium, 3000
GSK Investigational Site
Wilrijk, Belgium, 2610
GSK Investigational Site
Yvoir, Belgium, 5530
Canada, Alberta
GSK Investigational Site
Calgary, Alberta, Canada, T2N 4N2
Canada, British Columbia
GSK Investigational Site
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Nova Scotia
GSK Investigational Site
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
GSK Investigational Site
Hamilton, Ontario, Canada, L8V 5C2
GSK Investigational Site
London, Ontario, Canada, N6A 4L6
GSK Investigational Site
Oshawa, Ontario, Canada, L1G 2B9
GSK Investigational Site
Ottawa, Ontario, Canada, K1H 8L6
GSK Investigational Site
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
GSK Investigational Site
Montreal, Quebec, Canada, H2L 4M1
GSK Investigational Site
Montreal, Quebec, Canada, H2W 1S6
Czech Republic
GSK Investigational Site
Hradec Kralove, Czech Republic, 500 05
GSK Investigational Site
Ostrava, Czech Republic, 708 52
GSK Investigational Site
Praha 2, Czech Republic, 128 08
GSK Investigational Site
Zlin, Czech Republic, 76275
France
GSK Investigational Site
Boulogne-Billancourt, France, 92100
GSK Investigational Site
Grenoble, France, 38043
GSK Investigational Site
Montpellier, France, 34295
GSK Investigational Site
Nantes, France, 44093
GSK Investigational Site
Paris Cedex 10, France, 75475
GSK Investigational Site
Pierre-Bénite cedex, France, 69495
GSK Investigational Site
Rennes, France, 35042
GSK Investigational Site
Tours, France, 37044
GSK Investigational Site
Villejuif, France, 94805
Germany
GSK Investigational Site
Heidelberg, Baden-Wuerttemberg, Germany, 69120
GSK Investigational Site
Mannheim, Baden-Wuerttemberg, Germany, 68167
GSK Investigational Site
Tuebingen, Baden-Wuerttemberg, Germany, 72076
GSK Investigational Site
Muenchen, Bayern, Germany, 80804
GSK Investigational Site
Wuerzburg, Bayern, Germany, 97080
GSK Investigational Site
Buxtehude, Niedersachsen, Germany, 21614
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45122
GSK Investigational Site
Dresden, Sachsen, Germany, 01307
GSK Investigational Site
Luebeck, Schleswig-Holstein, Germany, 23538
GSK Investigational Site
Berlin, Germany, 10117
Greece
GSK Investigational Site
Athens, Greece, 11527
GSK Investigational Site
Athens, Greece, 185 47
GSK Investigational Site
Thessaloniki, Greece, 564 29
Italy
GSK Investigational Site
Milano, Lombardia, Italy, 20132
GSK Investigational Site
Milano, Lombardia, Italy, 20141
GSK Investigational Site
Milano, Lombardia, Italy, 20133
GSK Investigational Site
Pisa, Toscana, Italy, 56126
New Zealand
GSK Investigational Site
Christchurch, New Zealand, 8011
GSK Investigational Site
Dunedin, New Zealand, 9016
GSK Investigational Site
Newtown, Wellington, New Zealand, 6002
Norway
GSK Investigational Site
Oslo, Norway, 0310
Poland
GSK Investigational Site
Poznan, Poland, 61-866
GSK Investigational Site
Warszawa, Poland, 02-781
GSK Investigational Site
Warszawa, Poland, 04-125
Russian Federation
GSK Investigational Site
Chelyabinsk, Russian Federation, 454087
GSK Investigational Site
Magnitogorsk, Russian Federation, 455001
GSK Investigational Site
Moscow, Russian Federation, 115478
GSK Investigational Site
St. Petersburg, Russian Federation, 197758
Sweden
GSK Investigational Site
Göteborg, Sweden, SE-413 45
GSK Investigational Site
Linköping, Sweden, SE-581 85
GSK Investigational Site
Lund, Sweden, SE-221 85
GSK Investigational Site
Stockholm, Sweden, SE-171 76
GSK Investigational Site
Uppsala, Sweden, SE-751 85
Switzerland
GSK Investigational Site
Zürich, Switzerland, 8091
Ukraine
GSK Investigational Site
Dnepropetrovsk, Ukraine, 49102
GSK Investigational Site
Kharkiv, Ukraine, 61070
GSK Investigational Site
Kyiv, Ukraine, 03115
GSK Investigational Site
Kyiv, Ukraine, 03022
GSK Investigational Site
Lviv, Ukraine, 79031
GSK Investigational Site
Sumy, Ukraine, 40005
GSK Investigational Site
Sympheropol, Ukraine, 95023
GSK Investigational Site
Ternopil, Ukraine, 46023
GSK Investigational Site
Uzhgorod, Ukraine, 88017
United Kingdom
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom, CB2 2QQ
GSK Investigational Site
Northwood, Middlesex, United Kingdom, HA6 2RN
GSK Investigational Site
Sutton, Surrey, United Kingdom, SM2 5PT
GSK Investigational Site
Aberdeen, United Kingdom, AB25 2ZN
GSK Investigational Site
Birmingham, United Kingdom, B15 2TH
GSK Investigational Site
Chelmsford, United Kingdom, CM1 7ET
GSK Investigational Site
Leeds, United Kingdom, LS9 7TF
GSK Investigational Site
London, United Kingdom, SW3 6JJ
GSK Investigational Site
London, United Kingdom, W1G 6AD
GSK Investigational Site
Manchester, United Kingdom, M20 4BX
GSK Investigational Site
Oxford, United Kingdom, OX3 7LJ
GSK Investigational Site
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01245062     History of Changes
Other Study ID Numbers: 114267
Study First Received: November 18, 2010
Results First Received: February 14, 2013
Last Updated: October 17, 2013
Health Authority: Australia: Human Research Ethics Committee
United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by GlaxoSmithKline:
MEK inhibitor
Cancer
Metastatic Melanoma
BRAF mutant metastatic melanoma
GSK1120212

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on July 08, 2014