Nilotinib Plus Dabrafenib/Trametinib in Metastatic Melanoma

  • STATUS
    Recruiting
  • End date
    Mar 31, 2027
  • participants needed
    15
  • sponsor
    Peng Wang, MD PhD
Updated on 7 October 2022

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. Additionally, this study will assess pharmacokinetic parameters of dabrafenib and nilotinib when used in combination.

Description

This is a phase 1 dose-escalation study of nilotinib in combination with a fixed-dose of dabrafenib and trametinib. The first week, patients will be treated with dabrafenib (150mg, twice daily) and trametinib (2mg, once 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.

Details
Condition Metastatic Melanoma, BRAF Gene Mutation
Treatment Dabrafenib, Trametinib, Nilotinib 100mg, Nilotinib 200mg, Nilotinib 300mg, Nilotinib 400mg
Clinical Study IdentifierNCT04903119
SponsorPeng Wang, MD PhD
Last Modified on7 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients must have histologically confirmed metastatic or unresectable melanoma
Patients must have a BRAF V600 mutation
Patients must have failed any BRAFi/MEKi regimen to qualify for the trial
Age ≥18 years
ECOG performance status ≤ 1
Patients must have adequate organ and marrow function
Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible
HBV viral load must be undetectable on suppressive therapy, if indicated
Patients must have an undetectable HCV viral load
Patients with treated brain metastases are eligible if follow-up brain imaging 4 weeks or longer after central nervous system (CNS)-directed therapy shows no evidence of progression
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment
women of childbearing potential and men must agree to use adequate contraception
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Patients with chronic hypokalemia or chronic hypomagnesemia
Patients with long QT syndrome or baseline QTc (Fridericia) >470 msec in males and >480 msec in females
Patients who are receiving any other investigational therapies that could affect the primary or secondary outcomes of this study
Untreated brain metastases
History of allergic reactions attributed to compounds of similar chemical or biologic composition to nilotinib, dabrafenib, and trametinib
Patients receiving any medications or substances that are strong CYP3A or CYP2C8 inhibitors or substances that are strong CYP3A inducers
Use of Proton pump inhibitors concurrent with nilotinib
Use of drugs or substances known to prolong QT interval is prohibited with Nilotinib
Patients with uncontrolled intercurrent illness
Patients with psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or lactating women
Other prior malignancy active within 2 years, except for localized prostate cancer, cervical carcinoma in situ, non-melanoma carcinoma of the skin, stage 1 differentiated thyroid cancer or ductal carcinoma in situ of the breast that has/have undergone curative surgery or radiation
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