LGX818 in Combination With Agents (MEK162; BKM120; LEE011; BGJ398; INC280) in Advanced BRAF Melanoma

NCT ID: NCT01820364

Last Updated: 2017-01-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2015-03-31

Brief Summary

The primary purpose of the Phase II CLGX818X2102 study is to assess the anti-tumor activity of LGX818 in combination with selected agents.

Detailed Description

This is a phase II two part multi-center, open-label study. Part I: LGX818 single agent treatment until progression Part II: Combination treatments of LGX818 + MEK162, or BKM120, or BGJ398, or INC280, or LEE01 to assess the clinical efficacy, to further evaluate the safety of the drug combinations in patients with locally advanced or metastatic BRAF mutant melanoma after relapse on LGX818, and to determine the maximum tolerated dose of the combinations (when not established previously). These drug combinations are selected and assigned to patients based on documentation of molecular resistance mechanism.

Patients with BRAF mutant melanoma treated by LGX818 single agent in other studies can be enrolled directly in Part II of CLGX818X2102 after relapse.

Dose-escalations in the combination arms for which no MTD has been established will be based on the recommendations of a Bayesian logistic regression model guided by an escalation with overdose control criterion.

After careful evaluation of slow enrollment and the BRAF-mutant melanoma treatment landscape, recruitment was permanently halted on 26-Jul-2014.

This recruitment halt was not a consequence of any safety concern and patients who were ongoing in the study continued to be treated as per protocol.

Conditions

Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LGX818 single agent

Patients had to have written documentation of a BRAFV600 mutation, which was to have been obtained locally on a fresh tumor biopsy (preferred) or on the most recent archival tumor sample available.

Group Type: EXPERIMENTAL

LGX818

Intervention Type: DRUG

BRAF inhibitor. LGX818 was administered QD orally on a daily schedule (21-day cycles) as a flat-fixed dose and not by body weight or body surface area. LGX818 100 mg capsules and 50 mg capsules.

Interventions

LGX818

BRAF inhibitor. LGX818 was administered QD orally on a daily schedule (21-day cycles) as a flat-fixed dose and not by body weight or body surface area. LGX818 100 mg capsules and 50 mg capsules.

Intervention Type: DRUG

Other Intervention Names

encorafenib

Eligibility Criteria

Inclusion Criteria

• locally advanced or metastatic melanoma
• confirmed BRAF V600 mutation
• patients naïve to a selective BRAF inhibitor
• fresh tumor biopsy at baseline, and patient agrees for a mandatory biopsy at the time of relapse
• life expectancy ≥ 3 months
• World Health Organization (WHO) Performance Status ≤ 2.

Exclusion Criteria

• Previous treatment with RAF-inhibitor
• Symptomatic or untreated leptomeningeal disease
• Symptomatic brain metastases.
• Known acute or chronic pancreatitis
• Clinically significant cardiac disease
• AST/SGOT and ALT/SGPT > 2.5 x ULN, or > 5 x ULN if liver metastases are present
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral interventional drug
• Previous or concurrent malignancy.
• Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation

LGX818/MEK162:

History or current evidence of retinal disease History of Gilbert's syndrome.

LGX818/BKM120:

Patients with diabetes mellitus requiring insulin treatment Patient has mood disorders

LGX818/BGJ398:

History and/or current evidence of ectopic mineralization/ calcification Current evidence of corneal disorder/ keratopathy Patients with current evidence of endocrine alteration of calcium/phosphate homeostasis.

History of congenital long QT- syndrome and/or hypokalaemia CTCAE Grade ≥ 3 and/or magnesium levels below the clinically relevant lower limits before study entry.

Ionized (i) calcium (Ca) > ULN Serum inorganic phosphorus (Pi) > ULN

LGX818/LEE011 History of congenital long QT- syndrome and/or hypokalaemia CTCAE Grade ≥ 3 and/or magnesium levels below the clinically relevant lower limits before study entry.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Array BioPharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Array BioPharma

Role: STUDY_DIRECTOR

303-381-6604

Locations

Sarah Cannon Research Institute Onc Dept

Nashville, Tennessee, United States

Novartis Investigative Site

East Melbourne, Victoria, Australia

Novartis Investigative Site

Edmonton, Alberta, Canada

Novartis Investigative Site

Heidelberg, , Germany

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Zurich, , Switzerland

Countries

United States; Australia; Canada; Germany; Spain; Switzerland

Other Identifiers

2012-004798-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLGX818X2102

Identifier Type: -

Identifier Source: org_study_id