A Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma

This study is currently recruiting participants.
Verified January 2014 by Novartis
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
First received: April 14, 2011
Last updated: January 14, 2014
Last verified: January 2014

CLGX818X2101 is a first-time in-human, phase I study to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of daily administered LGX818 (daily, twice daily and/or every-other-day), a RAF kinase inhibitor. Patients with locally advanced or metastatic melanoma harboring the BRAF V600 mutation (during dose escalation phase and expansion phase) and patients with metastatic colorectal cancer harboring the BRAF V600 mutation (during the expansion phase) will be enrolled. The study consists of a dose escalation part were cohorts of patients will receive escalating oral doses of LGX818, followed by a safety dose expansion part were patients will be treated with oral dose of LGX818 given at the MTD or RP2D.

Condition Intervention Phase
Melanoma and Metastatic Colorectal Cancer
Drug: LGX818
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Multicenter, Open-label, Dose-escalation Study of Oral LGX818 in Adult Patients With Locally Advanced or Metastatic BRAF Mutant Melanoma

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Incidence of Dose Limiting Toxicities [ Time Frame: Approximately every 8 weeks (up to 2 years) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number and nature of Adverse events and clinical activity [ Time Frame: Approximately 3 years ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic profile of LGX818 [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
    LGX818 Plasma concentration

  • Tumor response per RECIST [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
    This includes duration of response, time to response, progression free survival and overall survival.

  • Baseline molecular status [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
    Baseline molecular status (mutation/ amplification/ expression) in tumor tissue of potential predictive markers

Estimated Enrollment: 126
Study Start Date: September 2011
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LGX818 - Dose escalation Drug: LGX818
Experimental: LGX818 - Dose Expansion at MTD or RP2D Drug: LGX818


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

For the dose escalation phase:

  1. Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]). For the dose expansion phase: (i) Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or (ii) confirmed diagnosis and non-resectable advanced metastatic colorectal cancer (mCRC) for which no further effective standard therapy exists.
  2. Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation.
  3. Evidence of measurable disease

Exclusion Criteria:

  1. Previous therapy with a MEK inhibitor.
  2. Symptomatic or untreated leptomeningeal disease.
  3. Symptomatic or untreated brain metastasis.Patients previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll. Brain metastasis must be stable with verification by imaging.
  4. Known acute or chronic pancreatitis.
  5. Clinically significant cardiac disease
  6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818
  7. Previous or concurrent malignancy. Exceptions to this exclusion criteria include: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to study entry; or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
  8. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
  9. History of thromboembolic or cerebrovascular events within the last 6 months

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01436656

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

United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Moffitt SC Recruiting
Tampa, Florida, United States, 33612
Contact: Lawrence Mckinney    813-745-6202    lawrence.mckinney@moffitt.org   
Principal Investigator: Amit Mahipal         
United States, Massachusetts
Massachusetts General Hospital Mass General 2 Active, not recruiting
Boston, Massachusetts, United States, 02114
Australia, New South Wales
Novartis Investigative Site Recruiting
Westmead, New South Wales, Australia, 2145
Australia, Victoria
Novartis Investigative Site Recruiting
Melbourne, Victoria, Australia, 3002
Novartis Investigative Site Recruiting
Toulouse Cedex 3, France, 31052
Novartis Investigative Site Recruiting
Villejuif Cedex, France, 94805
Novartis Investigative Site Active, not recruiting
Chuo-ku, Tokyo, Japan
Novartis Investigative Site Active, not recruiting
Oslo, Norway, NO-0379
Novartis Investigative Site Active, not recruiting
Barcelona, Cataluña, Spain, 08035
Novartis Investigative Site Recruiting
Barcelona, Cataluña, Spain, 08036
Novartis Investigative Site Recruiting
Madrid, Spain, 28050
Novartis Investigative Site Recruiting
Chur, Switzerland, 7000
Novartis Investigative Site Completed
Zuerich, Switzerland, 8091
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01436656     History of Changes
Other Study ID Numbers: CLGX818X2101, 2011-000556-42
Study First Received: April 14, 2011
Last Updated: January 14, 2014
Health Authority: United States: Food and Drug Administration
France: ANSM
Norway: NOMA
Switzerland: Swiss Medic
Spain: Agencia Espa?ola de Medicamentos y Productos Sanitarios

Keywords provided by Novartis:
BRAF mutant,
BRAF mutated,
RAF kinase inhibitor
BRAF V600 mutation

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on April 22, 2014