Clinical trial NCT01972347 (phase 2, status: active, not recruiting)
Conditions: melanoma
ICD codes: C43.0, C43.31, D03.9, C43.51, C43.9, D03.0, C43.4
Drugs: dabrafenib, trametinib
SMILES: CC(C)(C)C1=NC(=C(S1)C1=NC(N)=NC=C1)C1=C(F)C(NS(=O)(=O)C2=C(F)C=CC=C2F)=CC=C1, CN1C(=O)C(C)=C2N(C(=O)N(C3CC3)C(=O)C2=C1NC1=CC=C(I)C=C1F)C1=CC(NC(C)=O)=CC=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥18 years

          -  Histologically confirmed AJCC Stage IIIB or IIIC (Tx, T1-4, N1b, N2b, N2c, N3, Mo)
             cutaneous melanoma or unknown primary determined to be BRAF V600 mutation positive,
             with sufficient nodal or in-transit disease to enable biopsies prior to
             surgery.Patients must have disease that is measurable per RECIST version 1.1

          -  Able to swallow and retain oral medication and must not have any clinically
             significant gastrointestinal abnormalities that may alter absorption

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

          -  Adequate baseline organ function

          -  Women of childbearing potential must have a negative serum pregnancy test within 7
             days of first dose of study treatment and agree to use effective contraception from 14
             days prior to commencing study treatment, throughout the treatment period and for 4
             months after the last dose of study treatment

          -  Men with any female partner of childbearing potential must agree to use effective
             contraception from 14 days prior to commencing study treatment, throughout the
             treatment period and for 4 months after the last dose of study treatment

        Exclusion Criteria:

          -  Known mucosal or ocular melanoma or any unresectable in-transit metastases

          -  Evidence of distant metastatic disease on screening evaluation

          -  Prior anti-cancer treatment for melanoma (chemotherapy, immunotherapy, biologic
             therapy, vaccine therapy, investigational treatment or radiotherapy). Prior surgery
             for melanoma is allowed.

          -  Taken an investigational drug within 28 days or 5 half-lives, whichever is longer,
             prior to commencing study treatment.

          -  Current or expected use of a prohibited medication(s)

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to the study treatments, their excipients, and/or dimethyl
             sulfoxide (DMSO)

          -  Known HIV

          -  A history of known glucose-6-phosphate dehydrogenase (G6PD) deficiency

          -  History of another malignancy or a concurrent malignancy except:

               1. Patients who have been disease-free for 3 years and have a life expectancy of > 5
                  years;

               2. Patients with a history of completely resected non-melanoma skin cancer or
                  successfully treated in situ carcinoma are eligible, for example cervical cancer
                  in situ, atypical melanocytic hyperplasia or melanoma in situ, multiple primary
                  melanomas.

          -  A history or evidence of cardiovascular risk including any of the following: a. QT
             interval corrected for heart rate using the Bazett's formula ≥480 msec or ≥ 450 msec
             for patients with bundle branch block; b. History or evidence of current clinically
             significant uncontrolled arrhythmias; c. History of acute coronary syndromes
             (including myocardial infarction or unstable angina), coronary angioplasty, or
             stenting within 6 months prior to commencement of study treatment; d. History or
             evidence of current ≥ Class II congestive heart failure; e. Abnormal cardiac valve
             morphology documented by echocardiogram which in the opinion of the investigator could
             interfere with the patient's safety.

             f. Treatment refractory hypertension defined as a blood pressure of systolic > 140 mm
             Hg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive
             therapy.

          -  A history or current evidence/risk of retinal vein occlusion (RVO) or central serous
             retinopathy (CSR)

          -  Any serious or unstable pre-existing medical conditions (aside from the malignancy
             exceptions specified above), psychiatric disorders, or other conditions that, in the
             opinion of the treating clinician, could interfere with the patient's safety,
             obtaining informed consent, or compliance with study procedures.

          -  Breastfeeding females