A Phase 1 Study of Nilotinib in Combination With Dabrafenib and Trametinib or Encorafenib/Binimetinib in BRAF V600 Mutant Metastatic Melanoma After Progression on BRAF/MEK Inhibition

Who is this study for? Patients with BRAF V600 mutant metastatic melanoma
What treatments are being studied? Nilotinib+Dabrafenib+Trametinib
Status: Recruiting
Location: See all (4) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

This is a phase 1 dose-escalation study of nilotinib in combination with fixed-dose dabrafenib and trametinib regimen for patients with metastatic or unresectable melanoma carrying a BRAF V600 mutation and have relapsed on a BRAF/MEK inhibitor therapy. The goal is to assess the toxicity and tolerability and determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of the combination of nilotinib with dabrafenib and trametinib or with encorafenib and binimetinib. Additionally, this study will assess pharmacokinetic parameters of dabrafenib and nilotinib when used in combination.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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 CLIA-certified mutation testing is acceptable to document mutation status.

• Patients must have stable disease on dabrafenib and trametinib or on encorafenib and binimetinib for a duration of greater than or equal to 3 months OR have failed any BRAFi/MEKi regimen to qualify for the trial, including the dabrafenib/trametinib combination and/or the encorafenib/ binimetinib combination.

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

• Age ≥18 years.

• ECOG performance status ≤ 1.

• Patients must have adequate organ and marrow function as defined below:

• absolute neutrophil count ≥1,500/mcL

• platelets ≥100,000/mcL

• total bilirubin ≤ institutional upper limit of normal (ULN)

• AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN

• creatinine ≤ institutional ULN OR

• glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m2.

• Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral 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, encorafenib, dabrafenib, binimetinib and trametinib on the developing human fetus are unknown, women of childbearing potential and men must agree to use adequate contraception (non-hormonal 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.

Locations
United States
Iowa
University of Iowa
NOT_YET_RECRUITING
Iowa City
Kentucky
Markey Cancer Center
RECRUITING
Lexington
Pennsylvania
St. Luke's University Health Network
RECRUITING
Easton
Tennessee
Vanderbilt-Ingram Cancer Center
RECRUITING
Nashville
Contact Information
Primary
Yvonne Taul, RN
Yvonne.Taul@uky.edu
859-323-7628
Time Frame
Start Date: 2022-06-01
Estimated Completion Date: 2029-06-01
Participants
Target number of participants: 30
Treatments
Experimental: Level 1
Patients in this group will receive 100mg Nilotinib PO BID.
Experimental: Level 2
Patients in this group will receive 200mg Nilotinib PO BID.
Experimental: Level 3
Patients in this group will receive 300mg Nilotinib PO BID.
Experimental: Level 4
Patients in this group will receive 400mg Nilotinib PO BID.
Authors
Related Therapeutic Areas
Sponsors
Collaborators: National Cancer Institute (NCI), Novartis
Leads: Ruta Arays

This content was sourced from clinicaltrials.gov

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