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

ConditionsMetastatic MelanomaBRAF Gene Mutation
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorRina Plattner

About 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

None

Disqualifiers

None

Trial design

Design model

Sequential

Treatments tested in this trial

  • 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

Treatment groups

30 Participants
are divided into 4 treatment groups
Group A: Level 1Experimental treatment 5 interventions
Group B: Level 2Experimental treatment 5 interventions
Group C: Level 3Experimental treatment 5 interventions
Group D: Level 4Experimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

Percentage of Patients Experiencing Dose Limiting Toxicities

Percentage of patients who experienced dose-limiting toxicities associated with Nilotinib as defined by the study protocol.

Time frame
28 days

Secondary outcomes

1

Dose-Adjusted Steady State Concentration of Dabrafenib

The dose-adjusted steady state concentrations (Css) of dabrafenib will be calculated on day 8 (dabrafenib alone) compared to day 15 (dabrafenib + nilotinib).

Time frame
15 days
2

Change in Nilotinib Concentration

Plasma concentrations of Nilotinib will be measured on day 8 (pre-Nilotinib) and day 29.

Time frame
1 month
3

Duration of Response

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.

Time frame
12 months

Other outcomes

Sponsors and contacts

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Rina Plattner

Lead sponsor

University of Kentucky

Sponsor institution

Novartis

Collaborator

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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