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

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.

Conditions

• Metastatic Melanoma
• BRAF Gene Mutation

Interventions

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

Sponsors & Collaborators

• Novartis

  collaborator INDUSTRY

• National Cancer Institute (NCI)

  collaborator NIH

• Rina Plattner

  lead OTHER

Principal Investigators

• Ruta Arays, MD · University of Kentucky

• Rina Plattner, PhD · University of Kentucky

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-06-01

Primary Completion

2028-07-01

Completion

2030-06-01

FDA Drug

Yes

Countries

• United States

Study Locations