An access study of Trametinib for patients with advanced unresectable (stage IIIc) or distant metastatic (stage IV) BRAF V600E/K mutation positive cutaneous melanoma
- Conditions
- Metastatic melanoma with mutation BRAF V 600MedDRA version: 17.1Level: LLTClassification code 10027481Term: Metastatic melanomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-005149-40-FR
- Lead Sponsor
- aboratoire GlaxoSmithKline
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 400
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1. Signed, written informed consent. Age =18 years.
2. Has histologically confirmed cutaneous melanoma BRAF V600E/K positive mutation either unresectable (stage IIIc) or distant metastatic (stage IV).
3. Is not eligible for enrolment in any other ongoing relevant hypothesis testing clinical study for metastatic melanoma [...]
4. 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.
5. Is able to swallow and retain oral medication.
6. For patients with active brain metastases: the patient does not require or is ineligible for immediate local treatment.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 and in stable clinical condition. (Refer to Appendix 2 Section 12.2)
NOTE: patient in rapidly deteriorating clinical condition prior to start of therapy should not be considered for this open label access study. ECOG 3 patients may be included provided the patient is clinically stable on the investigator’s judgement.
8. Does not require treatment with another anti-cancer therapy while on this open label access study (except dabrafenib if in combination with trametinib).
9. Does not require treatment with prohibited concomitant medications (see Section 6.7.2).
10. 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 patient at high risk for an adverse outcome.
11. Where applicable, female patients of childbearing potential must agree to use one of the contraceptive methods listed below. These patients 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. 11. 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 patient at high risk for an adverse outcome.
12. For patients enrolled in France: a patient will be eligible for inclusion in this study only if he is, either affiliated to or beneficiary of a social security category.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. Patients who have received prior therapy with a MEK or BRAF inhibitor.
NOTE: However patients may be eligible in the following cases:
• Patients whose tumor has not progressed based on radiographic and clinical assessments. Such patients 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 (see Section 6.7 concomitant medications)
- trametinib monotherapy if the patient has benefited from a treatment with a BRAF-inhibitor without progression but cannot receive it anymore due to tolerability reason
• Patients who have met the criteria for disease progression may receive trametinib in combination with dabrafenib if:
1) 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.
2) no treatment-related grade 4 AEs or any SAEs occurred during the last 4 weeks of treatment.
2. Concurrent treatment with other systemic anti-cancer therapies is not allowed (except dabrafenib in combination with trametinib). Patients 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).
3. Presence of malignancy other than melanoma within 1 year of enrolment into this program or any malignancy with confirmed activating RAS mutation. Patient 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.
4. 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).
5. Current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
6. 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 > or = 480 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 (NYHA; Appendix 5 Section 12.5).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The objective of this open label access study is to provide access to trametinib to patients with histologically confirmed cutaneous melanoma with a BRAF V600E/K positive mutation that is either advanced unresectable (stage IIIc) or distant metastatic (stage IV), who require treatment with trametinib, either as monotherapy or in combination with dabrafenib. ;Secondary Objective: To describe the frequency and proportion of adverse events (AEs), serious adverse events (SAEs) related to treatment or leading to treatment discontinuation, and response rates to treatment determined clinically and/or radiologically by the investigator.;Primary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Adverse events (AEs), the serious adverse events (SAEs) related to treatment <br>- AE/SAE leading to discontinuation of treatment <br>- Response to treatment determined clinically and/or radiologically by the investigator.;Timepoint(s) of evaluation of this end point: - For AE/SAE: on an on-going basis and every 4 weeks during 6 months and every 8 weeks thereafter.<br>- Response to treatment: as per clinical practice <br>