Nilotinib + Dabrafenib/Trametinib for Melanoma
What You Need to Know Before You Apply
What is the purpose of this trial?
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.
Will I have to stop taking my current medications?
The trial requires that you stop taking any medications that are strong CYP3A or CYP2C8 inhibitors, as well as proton pump inhibitors and drugs that prolong the QT interval. You should discuss your current medications with the trial team to ensure they don't interact with the study drugs.
Is the combination of Nilotinib, Dabrafenib, and Trametinib safe for humans?
What makes the drug combination of Nilotinib, Dabrafenib, and Trametinib unique for treating melanoma?
This drug combination is unique because it combines Nilotinib, a drug not typically used for melanoma, with Dabrafenib and Trametinib, which target specific mutations in the BRAF gene and the MAPK pathway, potentially offering a novel approach for patients with BRAF-mutant melanoma who may not respond to standard treatments.13678
What data supports the effectiveness of the drug combination of Nilotinib, Dabrafenib, and Trametinib for melanoma?
Research shows that the combination of dabrafenib and trametinib is effective in treating advanced melanoma with a specific BRAF mutation, improving survival rates and reducing tumor size. This combination is well-tolerated and offers a significant treatment option for patients with this type of melanoma.1391011
Who Is on the Research Team?
Ruta Arays, MD
Principal Investigator
University of Kentucky
Are You a Good Fit for This Trial?
Adults with metastatic or unresectable melanoma and a BRAF V600 mutation who have not responded to previous BRAFi/MEKi therapy can join. They must be HIV, HBV, and HCV undetectable if applicable, have treated brain metastases without progression, good organ function, no severe heart issues, and agree to use contraception.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Initial Treatment
Participants receive dabrafenib and trametinib or encorafenib and binimetinib for the first week to achieve steady-state levels
Dose-Escalation Treatment
Nilotinib is added to the treatment regimen, and all three drugs are dosed concurrently. Pharmacokinetic samples and biopsies are collected.
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- Dabrafenib
- Nilotinib
- Trametinib
Dabrafenib is already approved in European Union, United States, Canada, Japan for the following indications:
Find a Clinic Near You
Who Is Running the Clinical Trial?
Ruta Arays
Lead Sponsor
Peng Wang, MD PhD
Lead Sponsor
Jill M Kolesar
Lead Sponsor
Novartis
Industry Sponsor
Vasant Narasimhan
Novartis
Chief Executive Officer since 2018
MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government
Shreeram Aradhye
Novartis
Chief Medical Officer since 2022
MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania
National Cancer Institute (NCI)
Collaborator