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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01820364
First received: March 25, 2013
Last updated: April 26, 2014
Last verified: April 2014
  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:


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 ]

Estimated Enrollment: 100
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

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations
United States, Arizona
Mayo Clinic - Arizona Mayo Withdrawn
*see Various Departments*, Arizona, United States
United States, California
University of California at Los Angeles Onc Dept Withdrawn
Los Angeles, California, United States, 90095
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Onc Dept Withdrawn
Tampa, Florida, United States, 33612
United States, New York
Memorial Sloan Kettering Cancer Center Dept Oncology Not yet recruiting
New York, New York, United States, 10021
Contact: Armando Sanchez    646-888-4339    sanchea2@mskcc.org   
Principal Investigator: Michael K. Postow         
United States, Tennessee
Sarah Cannon Research Institute Onc Dept Recruiting
Nashville, Tennessee, United States, 37203
Contact    877-691-7274    CANN.askSarah@scresearch.net   
Principal Investigator: Jeffrey R. Infante         
Vanderbilt University Medical Center SC - Dept of Oncology . Withdrawn
Nashville, Tennessee, United States, 37232
United States, Texas
US Oncology Central Monitoring Withdrawn
Dallas, Texas, United States, 75246
Baylor Health Care System/Sammons Cancer Center Baylor Texas Oncology Withdrawn
Dallas, Texas, United States, 75246
Australia, New South Wales
Novartis Investigative Site Withdrawn
Westmead, New South Wales, Australia, 2145
Australia, Victoria
Novartis Investigative Site Recruiting
Melbourne, Victoria, Australia, 3002
Canada, Alberta
Novartis Investigative Site Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
France
Novartis Investigative Site Not yet recruiting
Toulouse Cedex 3, France, 31052
Novartis Investigative Site Not yet recruiting
Villejuif Cedex, France, 94805
Germany
Novartis Investigative Site Recruiting
Heidelberg, Germany, 69120
Novartis Investigative Site Recruiting
Muenchen, Germany, 80336
Netherlands
Novartis Investigative Site Withdrawn
Amsterdam, Netherlands, 1066 CX
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Madrid, Spain, 28050
Switzerland
Novartis Investigative Site Recruiting
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: April 26, 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
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 July 26, 2014