Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Melanoma

Disease Progression

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Nilotinib

Trametinib

Dabrafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Tyrosine

Patients in this group will receive 100mg Nilotinib PO BID.

Patients in this group will receive 200mg Nilotinib PO BID.

Patients in this group will receive 300mg Nilotinib PO BID.

Patients in this group will receive 400mg Nilotinib PO BID.

Patients will begin dabrafenib (150mg PO BID) and trametinib (2mg PO once daily) on day one and will continue for 28 days. After 7 days, nilotinib will be added at 100mg PO BID and will continue for 21 days. For each subsequent cycle, nilotinib will be given for 28 days.

Nilotinib 100mg

Patients will begin dabrafenib (150mg PO BID) and trametinib (2mg PO once daily) on day one and will continue for 28 days. After 7 days, nilotinib will be added at 200mg PO BID and will continue for 21 days. For each subsequent cycle, nilotinib will be given for 28 days.

Nilotinib 200mg

Patients will begin dabrafenib (150mg PO BID) and trametinib (2mg PO once daily) on day one and will continue for 28 days. After 7 days, nilotinib will be added at 300mg PO BID and will continue for 21 days. For each subsequent cycle, nilotinib will be given for 28 days.

Nilotinib 300mg

Patients will begin dabrafenib (150mg PO BID) and trametinib (2mg PO once daily) on day one and will continue for 28 days. After 7 days, nilotinib will be added at 400mg PO BID and will continue for 21 days. For each subsequent cycle, nilotinib will be given for 28 days.

Nilotinib 400mg

All patients will begin dabrafenib (150mg PO BID) on day one and will continue for 28 days.

All patients will begin trametinib (2mg PO once daily) on day one and will continue for 28 days.

Yvonne Taul, RN

Amy Grossman

Douglas B Johnson

Mark Evers, MD

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. Additionally, this study will assess pharmacokinetic parameters of dabrafenib and nilotinib when used in combination.

This is a phase 1 dose-escalation study of nilotinib in combination with a fixed-dose of dabrafenib and trametinib. The first week, patients will be treated with dabrafenib (150mg, twice daily) and trametinib (2mg, once daily). After 7 days, when both drugs have achieved steady-state levels and there is maximal induction of CYP3A4, nilotinib will be added, and all three drugs dosed concurrently for the rest of the study. Plasma pharmacokinetic (PKs) samples for dabrafenib and nilotinib will be obtained at baseline, weekly for the first four weeks, and at regular study visits for the duration of the trial. Tissue core biopsies and correlative plasma samples will be obtained at baseline, and 2 weeks after the start of nilotinib.

Nilotinib Plus Dabrafenib/Trametinib in Metastatic Melanoma

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

Percentage of patients who experienced dose-limiting toxicities associated with Nilotinib as defined by the study protocol.

The dose-adjusted steady state concentrations (Css) of dabrafenib will be calculated on day 8 (dabrafenib alone) compared to day 15 (dabrafenib + nilotinib).

Plasma concentrations of Nilotinib will be measured on day 8 (pre-Nilotinib) and day 29.

Duration of overall response will be determined by the time measurement criteria are met for complete response (CR) or partial response (PR) - whichever is first recorded - until the first date that recurrent or progressive disease is objectively documented.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Nilotinib Plus Dabrafenib/Trametinib in Metastatic Melanoma	NCT04903119	Metastatic Mela... BRAF Gene Mutat...	Nilotinib 100mg Nilotinib 200mg Nilotinib 300mg Nilotinib 400mg Dabrafenib Trametinib	18 Years -	University of Kentucky
Nilotinib Plus Dabrafenib/Trametinib in Metastatic Melanoma	NCT04903119	Metastatic Mela... BRAF Gene Mutat...	Nilotinib 100mg Nilotinib 200mg Nilotinib 300mg Nilotinib 400mg Dabrafenib Trametinib	18 Years -	University of Kentucky

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