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

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 Drug: MEK162 Drug: LEE011 Drug: BGJ398 Drug: BKM120 Drug: INC280	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized 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

Genetic and Rare Diseases Information Center resources: APUDoma Carcinoid Tumor Neuroepithelioma

U.S. FDA Resources

Further study details as provided by Novartis:

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
Estimated Study Completion Date:	August 2016
Estimated Primary Completion Date:	August 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: LGX818 + MEK162 Rational combination of LGX818 + MEK162	Drug: LGX818 BRAF inhibitor Drug: MEK162 MAPK1/2 inhibitor
Experimental: LGX818 + LEE011 Rational combination of LGX818 + LEE011	Drug: LGX818 BRAF inhibitor Drug: LEE011 CDK4/6 inhibitor
Experimental: LGX818 + BGJ398 Rational combination of LGX818 + BGJ398	Drug: LGX818 BRAF inhibitor Drug: BGJ398 FGFR inhibitor
Experimental: LGX818 + BKM120 Rational combination of LGX818 + BKM120	Drug: LGX818 BRAF inhibitor Drug: BKM120 Pi3K inhibitor
Experimental: LGX818 + INC280 Rational combination of LGX818 + INC280	Drug: LGX818 BRAF inhibitor Drug: INC280 c-Met inhibitor

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
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

Novartis Pharmaceuticals

Investigators


Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information

No publications provided


Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01820364 History of Changes
Other Study ID Numbers:	CLGX818X2102, 2012-004798-17
Study First Received:	March 25, 2013
Last Updated:	December 15, 2014
Health Authority:	United States: Food and Drug Administration

Keywords provided by Novartis:


open-label study;BRAF inhibitor;LGX818;MEK162;LEE011;BGJ398;BKM120;INC280;MAPK1/2 inhibitor; Pi3K inhibitor; FGFR; c-Met; CDK4/6; metastatic melanoma;BRAF; V600

Additional relevant MeSH terms:


Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms, Germ Cell and Embryonal	Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas

ClinicalTrials.gov processed this record on March 01, 2015

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