RecruitingPhase 1NCT04903119

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


Sponsor

Rina Plattner

Enrollment

30 participants

Start Date

Jun 1, 2022

Study Type

INTERVENTIONAL

Conditions

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

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study tests whether adding nilotinib (a leukemia drug) to an existing combination of BRAF and MEK inhibitors can overcome resistance to treatment in people with metastatic melanoma that has a specific genetic mutation (BRAF V600). **You may be eligible if...** - You have metastatic or inoperable melanoma confirmed by biopsy - Your tumor has a BRAF V600 mutation - You have been on dabrafenib/trametinib or encorafenib/binimetinib for at least 3 months with stable disease, OR your disease has previously progressed on one of these combinations - You are 18 or older and in reasonably good health (ECOG 0 or 1) **You may NOT be eligible if...** - Your tumor does not have a BRAF V600 mutation - You have serious heart problems (e.g., prolonged QT interval on an ECG) - Your liver, kidney, or blood counts are too low to safely receive treatment - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

Interested in this trial?

Get notified about updates and connect with the research team.

Interventions

DRUGNilotinib 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.

DRUGNilotinib 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.

DRUGNilotinib 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.

DRUGNilotinib 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.

DRUGDabrafenib

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

DRUGTrametinib

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

DRUGEncorafenib

encorafenib will be administered orally 450mg once daily for 28 consecutive days

DRUGBinimetinib

binimetinib will be administered orally 45mg twice daily for 28 consecutive days


Locations(4)

University of Iowa

Iowa City, Iowa, United States

Markey Cancer Center

Lexington, Kentucky, United States

St. Luke's University Health Network

Easton, Pennsylvania, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

View Full Details on ClinicalTrials.gov

For the most up-to-date information, visit the official listing.

Visit

NCT04903119


Related Trials