NCT04759846

Hepatic Impairment Study of Encorafenib in Combination With Binimetinib in BRAF Melanoma

'An Open Label, Multicentre, Phase I Study to Evaluate the Impact of Moderate and Severe Hepatic Impairments on the Pharmacokinetics and Safety of Encorafenib in Combination With Binimetinib in Adult Patients With Unresectable or Metastatic BRAF V600-mutant Solid Tumors'.

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Pierre Fabre Medicament · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Encorafenib in combination with binimetinib have been approved in USA, Europe, Australia, Japan and Switzerland for the treatment of adult patients with unresectable or metastatic melanoma with BRAF V600 mutation. The main objective of this study is to find a safe and effective dose of encorafenib in combination with binimetinib for patients who have BRAF-mutant metastatic or unresectable melanoma with hepatic dysfunction (i.e. moderate or severe impairment).

Detailed description

This is an open label, multicentre, phase I study to evaluate the impact of moderate and severe hepatic impairment (HI) on the pharmacokinetics and safety of encorafenib in combination with binimetinib, in adult patients with unresectable or metastatic BRAF V600-mutant melanoma. For each participant, the treatment period will be split in 2 phases: * a HI assessment phase assessing the impact of hepatic impairment after a single dose (Day 1) and after repeated doses (Day 15). * a post-HI assessment phase: after completing the HI assessment phase, participants may continue treatment in the post-HI assessment phase until disease progression or unacceptable toxicity. Participants with hepatic impairment will be enrolled sequentially according to their severity. The study will start first in participants with normal hepatic function and moderate hepatic impairment respectively. Participants will be assigned to one of the following 3 study groups: * Group with normal hepatic function: 4 participants * Group with moderate hepatic impairment (Child-Pugh Class B): 4 participants * Group with severe impairment (Child-Pugh Class C): 4 participants An Internal Review Committee (IRC) will review the safety and PK data of encorafenib in combination with binimetinib for group with normal hepatic function and group with moderate hepatic impairment and make a recommendation prior to start group with severe impairment enrolment. The Sponsor will determine whether it is safe and feasible to proceed with group with severe impairment. Participants will receive treatment doses according to their assigned group.

Conditions

• BRAF V600 Mutation
• Unresectable Melanoma
• Metastatic Melanoma
• Hepatic Impairment

Interventions

Type	Name	Description
DRUG	Encorafenib + Binimetinib	The doses administered to patients with normal hepatic function will be the same as the recommended commercialised doses
DRUG	Encorafenib + Binimetinib	A smaller dose than the dose approved for patients with normal hepatic function has been defined
DRUG	Encorafenib + Binimetinib	A smaller dose than the dose approved for patients with normal hepatic function has been defined

Timeline

• Start date: 2021-01-21
• Primary completion: 2023-05-01
• Completion: 2023-05-01
• First posted: 2021-02-18
• Last updated: 2023-02-21

Locations

7 sites across 3 countries: Czechia, Italy, Spain