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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Array BioPharma
ClinicalTrials.gov Identifier:
NCT01820364
First received: March 25, 2013
Last updated: February 11, 2016
Last verified: February 2016
History of Changes
  Purpose
The primary purpose of the Phase II CLGX818X2102 study is to assess the anti-tumor activity of LGX818 in combination with selected agents.

Condition Intervention Phase
Melanoma
 Drug: LGX818
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II, Multi-center, Open-label Study of Single-agent LGX818 Followed by a Rational Combination With Agents After Progression on LGX818, in Adult Patients With Locally Advanced or Metastatic BRAF V600 Melanoma

Resource links provided by NLM:

MedlinePlus related topics: Melanoma
U.S. FDA Resources

Further study details as provided by Array BioPharma:

Primary Outcome Measures:
  • Overall response rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence and severity of adverse events [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Incidence rate of Dose Limiting Toxicities (DLTs) in Cycle 1 of Combination Part (Part II) [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Plasma concentration and derived PK parameters of LGX818 and combination partners [ Time Frame: 3years ] [ Designated as safety issue: Yes ]
  • Overall Response Rate (ORR) (Part I) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Progression Free Survival (PFS)(Part I and II) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Duration Of Response (DOR) (Part II) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Overall Survival (OS) (Part II) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Molecular status (mutation/amplification/expression) of markers relevant to the RAF/MEK/ERK and PI3K/AKT pathways [ Time Frame: baseline, at progression with LGX818 single agent treatment up to 3 years ] [ Designated as safety issue: No ]
Enrollment: 15
Study Start Date: November 2013
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
 Drug: 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.
Other Name: encorafenib

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

  Eligibility
Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

Specific exclusion criteria for each treatment arm:

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01820364

Locations
United States, Tennessee
Sarah Cannon Research Institute Onc Dept
Nashville, Tennessee, United States, 37203
Australia, Victoria
Novartis Investigative Site
East Melbourne, Victoria, Australia, 3002
Canada, Alberta
Novartis Investigative Site
Edmonton, Alberta, Canada, T6G 1Z2
Germany
Novartis Investigative Site
Heidelberg, Germany, 69120
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Switzerland
Novartis Investigative Site
Zuerich, Switzerland, 8091
Sponsors and Collaborators
Array BioPharma
Investigators
Study Director: Array BioPharma 303-381-6604
  More Information

Responsible Party: Array BioPharma
ClinicalTrials.gov Identifier: NCT01820364     History of Changes
Other Study ID Numbers: CLGX818X2102  2012-004798-17 
Study First Received: March 25, 2013
Last Updated: February 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Array BioPharma:
open-label study
BRAF inhibitor
LGX818
MEK1620
MAPK1/2 inhibitor
Pi3K inhibitor
 FGFR
c-Met
CDK4/6
metastatic melanoma
BRAF
V600

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
 Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on September 30, 2016