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Access Study of Trametinib for Subjects With Advanced Unresectable (Stage IIIc) or Distant Metastatic (Stage IV) BRAF V600E/K Mutation Positive Cutaneous Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02416232
Expanded Access Status : No longer available
First Posted : April 14, 2015
Last Update Posted : August 15, 2017
Information provided by (Responsible Party):

Brief Summary:
This is a single arm open label, multicenter, non randomized, access study of trametinib for subjects with histologically confirmed cutaneous melanoma with a BRAF V600E/K positive mutation that is either advanced unresectable (stage IIIc) or distant metastatic (stage IV). Trametinib may be given as monotherapy or in combination since first line metastatic melanoma as per inclusion criteria. Subjects who received prior BRAF inhibitor may be included if they have not progressed under such treatment or if they have presented limited progression as per eligibility criteria. It is estimated that between 250 and 400 subjects with histologically confirmed cutaneous melanoma with a BRAF V600E/K positive mutation that is either advanced unresectable (stage IIIc) or distant metastatic (stage IV) will be enrolled.

Condition or disease Intervention/treatment
Melanoma Drug: Trametinib Drug: Dabrafenib

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Study Type : Expanded Access
Official Title: An Open Label Non Randomized Access Study of Trametinib for Patients With Advanced Unresectable (Stage IIIc) or Distant Metastatic (Stage IV) BRAF V600E/K Mutation Positive Cutaneous Melanoma

Intervention Details:
  • Drug: Trametinib
    Trametinib will be provided as tablets containing 0.5 milligram (mg) or 2.0 mg of trametinib parent (present as the DMSO solvate). The starting dose of trametinib will be administered orally 2.0 mg, once daily (QD)
  • Drug: Dabrafenib
    Dabrafenib is commercially available as capsules containing 50 mg or 75 mg as free base (present as the mesylate salt). Dabrafenib will be administered orally 150 mg, twice daily (BID).

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All

Inclusion Criteria:

  • Provides signed and dated informed consent, with age at the time of consent >=18 years.
  • Has histologically confirmed cutaneous melanoma BRAF V600E/K positive mutation either unresectable (stage IIIc) or distant metastatic (stage IV).
  • Is not eligible for enrolment in any other ongoing relevant hypothesis testing clinical study for metastatic melanoma or, if eligible, is so geographically distant from a participating site that attending frequent clinic visits is not feasible.
  • Has not participated in the following GSK sponsored clinical studies (COMBI-v: MEK116513, COMBI-d: MEK115306, COMBI-AD: BRF115532) for melanoma indication prior to participating in this open label access study.
  • Is able to swallow and retain oral medication.
  • For subjects with active brain metastases: the subject does not require or is ineligible for immediate local treatment.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 and in stable clinical condition. NOTE: subject in rapidly deteriorating clinical condition prior to start of therapy should not be considered for this open label access study. ECOG 3 subjects may be included provided the subject is clinically stable on the investigator's judgement.
  • Does not require treatment with another anti-cancer therapy while on this open label access study (except dabrafenib if in combination with trametinib).
  • Does not require treatment with prohibited concomitant medications.
  • Does not have any medical conditions or physical examination or clinical laboratory findings which, in the opinion of the investigator and/or GSK Medical Monitor, would put the subject at high risk for an adverse outcome.
  • Where applicable, female subjects of childbearing potential must agree to use one of the contraceptive methods listed in the study protocol. These subjects must have a negative serum pregnancy test within 7 days prior to the first dose of trametinib, preferably as close to the first dose as possible, agree to use adequate contraception from the time of the pregnancy test, throughout the treatment period and for a total of 4 months following the last dose of treatment.
  • For subjects enrolled in France: a subject will be eligible for inclusion in this study only if he is, either affiliated to or beneficiary of a social security category.

Exclusion Criteria:

  • Subjects who have received prior therapy with a MEK or BRAF inhibitor. NOTE: However subjects may be eligible in the following cases: Subjects whose tumor has not progressed based on radiographic and clinical assessments. Such subjects may receive therapy with: trametinib in combination with dabrafenib (in case of an adverse event related to a previous BRAF or MEK inhibitor other than trametinib or dabrafenib and without cross-reaction anticipated, or if clinically indicated according to investigator judgement). Prior treatment (except trametinib and dabrafenib) should have been stopped for a period of 5 half lives or 28 days (whichever is shorter) before starting treatment of this study; trametinib monotherapy if the subject has benefited from a treatment with a BRAF-inhibitor without progression but cannot receive it anymore due to tolerability reason. Subjects who have met the criteria for disease progression may receive trametinib in combination with dabrafenib if: the disease progression was confirmed after a period of at least 6 months of clinical benefit (Response or Stable Disease) on monotherapy and if the progression was characterized by a limited radiographic progression in the absence of clinical signs and symptoms of progression. no treatment-related grade 4 AEs or any SAEs occurred during the last 4 weeks of treatment.
  • Concurrent treatment with other systemic anti-cancer therapies is not allowed (except dabrafenib in combination with trametinib). Subjects who are currently being treated with another systemic anti-cancer therapy (e.g. chemo, immune, biologic, or targeted therapy) must discontinue use prior to initiation of treatment in this open label access study for a period of 5 half lives or 28 days (whichever is shorter).
  • Presence of malignancy other than melanoma within 1 year of enrolment into this program or any malignancy with confirmed activating RAS mutation. Subject with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Note: Prospective RAS testing is not required. However, if the results of previous RAS testing are known, they must be used in assessing eligibility.
  • Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib or dabrafenib, or excipients or to dimethyl sulfoxide (DMSO).
  • Current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
  • Current evidence of cardiovascular risk including any of the following: Left Ventricular Ejection Fraction (LVEF) < lower limit of normal (LLN); A QT interval corrected for heart rate using the Bazett's formula >=480 millisecond (msec); Clinically significant uncontrolled arrhythmias; Acute coronary syndromes (including myocardial infarction and unstable angina); Congestive heart failure >=Class II as defined by New York Heart Association.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02416232

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GSK Investigational Site
Amiens Cedex, France, 80054
GSK Investigational Site
Angers, France, 49100
GSK Investigational Site
Bayonne cedex, France, 64109
GSK Investigational Site
Besancon cedex, France, 25030
GSK Investigational Site
Bobigny, France, 93000
GSK Investigational Site
Bordeaux, France, 33075
GSK Investigational Site
Boulogne-Billancourt, France, 92100
GSK Investigational Site
Brest cedex, France, 29609
GSK Investigational Site
Caen Cedex 9, France, 14033
GSK Investigational Site
Chambray-Les-Tours, France, 37170
GSK Investigational Site
Clermont-Ferrand cedex 1, France, 63003
GSK Investigational Site
Creteil, France, 94010
GSK Investigational Site
Dijon Cedex, France, 21079
GSK Investigational Site
Grenoble cedex 9, France, 38043
GSK Investigational Site
La Rochelle cedex 1, France, 17019
GSK Investigational Site
Le Havre, France, 76083
GSK Investigational Site
Le Mans, France, 72000
GSK Investigational Site
Lille, France, 59037
GSK Investigational Site
Limoges cedex, France, 87042
GSK Investigational Site
Lorient, France, 56322
GSK Investigational Site
Lyon Cedex 08, France, 69373
GSK Investigational Site
Marseille Cedex 5, France, 13385
GSK Investigational Site
Montpellier cedex 5, France, 34295
GSK Investigational Site
Montpellier Cedex 5, France, 34298
GSK Investigational Site
Mulhouse, France, 68100
GSK Investigational Site
Nantes Cedex 1, France, 44093
GSK Investigational Site
Nice, France, 06202
GSK Investigational Site
Nimes, France, 30029 cedex 9
GSK Investigational Site
Orleans Cedex 2, France, 45067
GSK Investigational Site
Paris Cedex 10, France, 75475
GSK Investigational Site
Paris, France, 75006
GSK Investigational Site
Pau, France, 64000
GSK Investigational Site
Pierre-Benite cedex, France, 69495
GSK Investigational Site
Poitiers, France, 86021
GSK Investigational Site
Pringy Cedex, France, 74374
GSK Investigational Site
Reims Cedex, France, 51092
GSK Investigational Site
Rennes Cedex, France, 35042
GSK Investigational Site
Rouen, France, 76031
GSK Investigational Site
Saint-Pierre, France, 97448
GSK Investigational Site
Saint-Priest en Jarez, France, 42270
GSK Investigational Site
Strasbourg Cedex, France, 67091
GSK Investigational Site
Thionville, France, 57126 Cedex 1
GSK Investigational Site
Toulouse Cedex 9, France, 31059
GSK Investigational Site
Valence Cedex 9, France, 26953
GSK Investigational Site
Vandoeuvre-Les-Nancy, France, 54511
GSK Investigational Site
Villejuif cedex, France, 94805
Sponsors and Collaborators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline Identifier: NCT02416232    
Other Study ID Numbers: 202105
First Posted: April 14, 2015    Key Record Dates
Last Update Posted: August 15, 2017
Last Verified: August 2017
Keywords provided by GlaxoSmithKline:
BRAF V600E/K mutation
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action