NCT04903119

Nilotinib Plus Dabrafenib/Trametinib or Encorafenib/Binimetinib in Metastatic Melanoma

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Rina Plattner · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This is a phase 1 dose-escalation study of nilotinib in combination with a fixed-dose of dabrafenib and trametinib or with encorafenib and binimetinib. The first week, patients will be treated with dabrafenib (150mg, twice daily) and trametinib (2mg, once daily), or encorafenib (450 mg, daily) and binimetinib (45 mg twice 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. Optional 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.

Conditions

• Metastatic Melanoma
• BRAF Gene Mutation

Interventions

Type	Name	Description
DRUG	Nilotinib 100mg	Patients will begin dabrafenib (150mg PO BID) and trametinib (2mg PO once daily) or encorafenib (450 mg PO) and binimetinib (45 mg PO BID) 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.
DRUG	Nilotinib 200mg	Patients will begin dabrafenib (150mg PO BID) and trametinib (2mg PO once daily) or encorafenib (450 mg PO) and binimetinib (45 mg PO BID) 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.
DRUG	Nilotinib 300mg	Patients will begin dabrafenib (150mg PO BID) and trametinib (2mg PO once daily) or encorafenib (450 mg PO) and binimetinib (45 mg PO BID) 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.
DRUG	Nilotinib 400mg	Patients will begin dabrafenib (150mg PO BID) and trametinib (2mg PO once daily) or encorafenib (450 mg PO) and binimetinib (45 mg PO BID) 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.
DRUG	Dabrafenib	All patients will begin dabrafenib (150mg PO BID) on day one and will continue for 28 days.
DRUG	Trametinib	All patients will begin trametinib (2mg PO once daily) on day one and will continue for 28 days.
DRUG	Encorafenib	encorafenib will be administered orally 450mg once daily for 28 consecutive days
DRUG	Binimetinib	binimetinib will be administered orally 45mg twice daily for 28 consecutive days

Timeline

• Start date: 2022-06-01
• Primary completion: 2028-07-01
• Completion: 2030-06-01
• First posted: 2021-05-26
• Last updated: 2026-02-13

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study