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

Conditions

• BRAF Gene Mutation
• Metastatic Melanoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

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

Study Details

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.

Key Dates

Start date

Jun 1, 2022

Status verified

Feb 2026

Primary completion

Jul 1, 2028

Completion

Jun 1, 2030

Study Design

Enrollment

30 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Level 1
  Patients in this group will receive 100mg Nilotinib PO BID.
• Experimental: Level 2
  Patients in this group will receive 200mg Nilotinib PO BID.
• Experimental: Level 3
  Patients in this group will receive 300mg Nilotinib PO BID.
• Experimental: Level 4
  Patients in this group will receive 400mg Nilotinib PO BID.

Primary Outcome Measure

Percentage of Patients Experiencing Dose Limiting Toxicities [ Time Frame: 28 days ]

Central Contacts

• Heather Pavlik, RN
  859-323-7628
  [email protected]

Locations (4)

Find similar trials in Iowa City, IA

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