Nilotinib Plus Dabrafenib/Trametinib or Encorafenib/Binimetinib in Metastatic Melanoma
- Conditions
- Metastatic MelanomaBRAF Gene Mutation
- Interventions
- Registration Number
- NCT04903119
- Lead Sponsor
- Ruta Arays
- Brief 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. 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Level 1 Nilotinib 100mg Patients in this group will receive 100mg Nilotinib PO BID. Level 1 Dabrafenib Patients in this group will receive 100mg Nilotinib PO BID. Level 1 Trametinib Patients in this group will receive 100mg Nilotinib PO BID. Level 1 Encorafenib Patients in this group will receive 100mg Nilotinib PO BID. Level 1 Binimetinib Patients in this group will receive 100mg Nilotinib PO BID. Level 2 Nilotinib 200mg Patients in this group will receive 200mg Nilotinib PO BID. Level 2 Dabrafenib Patients in this group will receive 200mg Nilotinib PO BID. Level 2 Trametinib Patients in this group will receive 200mg Nilotinib PO BID. Level 2 Encorafenib Patients in this group will receive 200mg Nilotinib PO BID. Level 2 Binimetinib Patients in this group will receive 200mg Nilotinib PO BID. Level 3 Nilotinib 300mg Patients in this group will receive 300mg Nilotinib PO BID. Level 3 Dabrafenib Patients in this group will receive 300mg Nilotinib PO BID. Level 3 Trametinib Patients in this group will receive 300mg Nilotinib PO BID. Level 3 Encorafenib Patients in this group will receive 300mg Nilotinib PO BID. Level 3 Binimetinib Patients in this group will receive 300mg Nilotinib PO BID. Level 4 Nilotinib 400mg Patients in this group will receive 400mg Nilotinib PO BID. Level 4 Dabrafenib Patients in this group will receive 400mg Nilotinib PO BID. Level 4 Trametinib Patients in this group will receive 400mg Nilotinib PO BID. Level 4 Encorafenib Patients in this group will receive 400mg Nilotinib PO BID. Level 4 Binimetinib Patients in this group will receive 400mg Nilotinib PO BID.
- Primary Outcome Measures
Name Time Method Percentage of Patients Experiencing Dose Limiting Toxicities 28 days Percentage of patients who experienced dose-limiting toxicities associated with Nilotinib as defined by the study protocol.
- Secondary Outcome Measures
Name Time Method Dose-Adjusted Steady State Concentration of Dabrafenib 15 days The dose-adjusted steady state concentrations (Css) of dabrafenib will be calculated on day 8 (dabrafenib alone) compared to day 15 (dabrafenib + nilotinib).
Change in Nilotinib Concentration 1 month Plasma concentrations of Nilotinib will be measured on day 8 (pre-Nilotinib) and day 29.
Duration of Response 12 months 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.
Trial Locations
- Locations (3)
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