"Dabrafenib and Trametinib in Circulating Free DNA BRAFV600 Mutated Metastatic Melanoma Patients: a Prospective Phase II, Open Label, Multicentre Study - (Bioliquid TAILOR Study - BIOTAILOR)"

Exclusion Criteria

• •1. Symptomatic brain metastases;
• •2. History of another malignancy, exception: subjects who have been disease-free for 3 years, (i.e. subjects with second malignancies that are indolent or definitively treated at least 3 years ago) or subjects with a history of completely resected nonmelanoma skin cancer;
• •3. A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy including:
• •* Presence of predisposing factors to RVO or central serous retinopathy (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes); or
• •* Visible retinal pathology as assessed by ophthalmic examination that is considered a risk factor for RVO or central serous retinopathy such as: i. Evidence of new optic disc cupping; ii. Evidence of new visual field defects on automated perimetry; iii. Intraocular pressure \>21 mmHg as measured by tonometry.
• •4. A history of clinically significant or active interstitial lung disease or pneumonitis;
• •5. Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the subject's safety, obtaining informed consent, or compliance with study procedures;
• •6. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (subjects with laboratory evidence of cleared HBV and HCV infection will be permitted);
• •7. A history or evidence of cardiovascular risk including any of the following:
• •* Current LVEF \< LLN;
• •* A QT interval corrected for heart rate using the Bazett's formula \>480 msec;
• •* A history or evidence of current clinically significant uncontrolled arrhythmias; Exception: Subjects with atrial fibrillation controlled for \> 30 days prior to enrollment are eligible;
• •* A history (within 6 months prior to enrollment) of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty;
• •* A history or evidence of current \>= Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines;
• •* Treatment refractory hypertension defined as a blood pressure of systolic\> 140 mmHg and/or diastolic \> 90 mm Hg which cannot be controlled by antihypertensive therapy;
• •* Patients with intra-cardiac defibrillators or permanent pacemakers;
• •* Known cardiac metastases;
• •* Abnormal cardiac valve morphology (\> grade 2) documented by echocardiogram (subjects with grade 1 abnormalities \[i.e., mild regurgitation/stenosis\] can be entered on study). Subjects with moderate valvular thickening should not be entered on study;
• •* Uncorrectable electrolyte abnormalities (e.g. hypokalaemia, hypomagnesaemia, hypocalcaemia), long QT syndrome or taking medicinal products known to prolong the QT interval.
• •8. Female subjects who are pregnant (positive pregnancy test), breast-feeding, or who are of childbearing potential and not practicing a reliable method of birth control;
• •9. Inability to regularly access site facilities for logistical or other reasons;
• •10. History of poor co-operation, non-compliance with medical treatment, or unreliability;
• •11. Participation in any interventional drug or medical device study within 30 days prior to treatment start.