1. Histologic diagnosis of unresectable or metastatic BRAF V600 mutant melanoma.
2. Age > 18 years.
3. Naïve or any number of prior systemic therapeutic regimens for unresectable stage III
or stage IV melanoma, except prior BRAF or MEK inhibitor agents. This includes
chemotherapy, immunotherapy, biochemotherapy, or investigational treatments. Patients
may also have received therapies in the adjuvant setting.
4. Performance status ECOG 0-2.
5. Adequate organ function as defined below:
A.- total bilirubin 3 x institutional upper limit of normal B.- AST(SGOT)/ALT(SPGT) ≤
5 X institutional upper limit of normal C.- creatinine 3 mg/dL D.- cardiac ejection
fraction > 50% E.- QTcF ≤ 480msec F.-PT/INR/aPTT ≤ 1.5 x institutional upper limit of
6. Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 4 months following completion of therapy.
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately. A female of child-bearing
potential is any woman (regardless of sexual orientation, having undergone a tubal
ligation, or remaining celibate by choice) who meets the following criteria: has not
undergone a hysterectomy or bilateral oophorectomy; or has not been naturally
postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in
the preceding 12 consecutive months).
7. All sites of disease must be evaluated within 4 weeks prior to beginning therapy.
Patients must have measurable disease as defined by RECIST v1.1 (see Section 6).
8. Ability to understand and the willingness to sign a written informed consent.
1. Subjects who have had chemotherapy or radiotherapy or any systemic therapy for
melanoma within 3 weeks prior to entering the study or those who have not recovered
from adverse events due to agents administered more than 3 weeks earlier. No
concomitant therapy is allowed including IL2, interferon, ipilimumab, anti-PD-1 or
anti-PD-L1 antibody, cytotoxic chemotherapy, immunosuppressive agents, or other
2. Active infection with hepatitis B or C or HIV.
3. Subjects with active CNS disease are excluded. Patient with brain metastases
previously treated with surgery or radiation therapy and with confirmed SD for >2
weeks are allowed.
4. Patients are excluded if they have a history of any other malignancy from which the
patient has been disease-free for less than 2 years, with the exception of adequately
treated and cured basal or squamous cell skin cancer, superficial bladder cancer or
carcinoma in situ of the cervix.
5. Uncontrolled inter-current illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure (>class II based on NYHA), unstable
angina pectoris, clinically significant and uncontrolled cardiac arrhythmia,
uncontrolled thyroid disease, or psychiatric illness/social situations that would
limit compliance with study requirements. Acute coronary syndrome within 24 weeks.
Note atrial fibrillation controlled >30 days is not an exclusion.
6. History of predisposition to retinal vein occlusion or central serous retinopathy.
7. Prior BRAF or MEK inhibitor therapy.
8. Wolff-Parkinson White syndrome or the presence of an intra-cardiac defibrillator (see
9. Known cardiac metastases.
10. History of interstitial lung disease or unresolved pneumonitis.
11. Immediate or delayed hypersensitivity to digoxin.
12. Patients requiring concomitant medications listed in section 4.3 that are not able to
be switched to a reasonable alternative.