Clinical Trials Search at Vanderbilt-Ingram Cancer Center

Inclusion Criteria:

Patients must have histologically confirmed metastatic or unresectable melanoma. Radiological evaluation should occur within 28-days prior to enrollment initiation

Patients must have a BRAF V600 mutation. Any Clinical Laboratory Improvement Act (CLIA)-certified mutation testing is acceptable to document mutation status

Patients must have stable disease on dabrafenib and trametinib for a duration of greater than or equal to 6 months OR have failed any BRAFi/MEKi regimen to qualify for the trial, including the dabrafenib/trametinib combination

Patient may have had prior immunotherapy for metastatic disease (although NOT mandatory). Other prior therapies are not allowed, with the exception of radiation

Age >= 18 years

Eastern Cooperative Oncology Group (ECOG) performance status = 1

Absolute neutrophil count >= 1,500/mcL

Platelets >= 100,000/mcL

Total bilirubin = institutional upper limit of normal (ULN)

Aspartate transaminase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine transaminase (ALT)(serum glutamate pyruvate transaminase [SGPT]) = 3 x institutional ULN

Creatinine = institutional ULN OR glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2

Patients with known human immunodeficiency virus (HIV) on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial

For patients with known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with known HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

Patients with treated brain metastases are eligible if follow-up brain imaging 4 weeks or longer after central nervous system (CNS)-directed therapy shows no evidence of progression

Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better

Measurable (target) disease by Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria. Target lesions selected for tumor measurements should be those where additional (e.g., palliative) treatments are not indicated or anticipated. * Measurable disease per RECIST 1.1 requirements: defined as longest diameter to be recorded for non-nodal lesions > 10mm and short axis for nodal lesions >15 mm using conventional techniques

The effects of nilotinib, dabrafenib, and trametinib on the developing human fetus are unknown, women of childbearing potential and men must agree to use adequate contraception (nonhormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of nilotinib, dabrafenib, and trametinib administration

Patients must have the ability to understand and the willingness to sign a written informed consent document



Exclusion Criteria:

Patients with chronic hypokalemia or chronic hypomagnesemia. Patients can be eligible with a repeat screening, if results show repletion

Patients with long QT syndrome or baseline QTc (Fridericia) > 470 msec in males and > 480 msec in females (ULN for each respectively)

Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1 or greater than baseline) with the exception of alopecia, grade 2 fatigue, vitiligo or endocrinopathies on stable replacement therapy)

Patients who are receiving any other investigational therapies that could affect the primary or secondary outcomes of this study

Untreated brain metastases are not allowed

History of allergic reactions attributed to compounds of similar chemical or biologic composition to nilotinib, dabrafenib, and trametinib

Patients receiving any medications or substances that are strong CYP3A or CYP2C8 inhibitors are ineligible for this trial. Patients receiving any medications or substances that are strong CYP3A inducers are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product

Use of proton pump inhibitors concurrent with nilotinib is prohibited. Use of short-acting antacids or H2 blockers as an alternative to proton pump inhibitors is allowable

Use of drugs or substances known to prolong QT interval is prohibited with nilotinib

Patients with uncontrolled intercurrent illness

Patients with psychiatric illness/social situations that would limit compliance with study requirements

Pregnant or lactating women

Other prior malignancy active within 2 years, except for localized prostate cancer, cervical carcinoma in situ, non-melanoma carcinoma of the skin, stage 1 differentiated thyroid cancer or ductal carcinoma in situ of the breast that has/have undergone curative surgery or radiation