Overview
Access Study of Trametinib for Subjects With Advanced Unresectable (Stage IIIc) or Distant Metastatic (Stage IV) BRAF V600E/K Mutation Positive Cutaneous Melanoma
Status:
No longer available
No longer available
Trial end date:
1969-12-31
1969-12-31
Target enrollment:
0
0
Participant gender:
All
All
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.Details
Lead Sponsor:
GlaxoSmithKlineTreatments:
Dabrafenib
Trametinib
Criteria
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.