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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01436656
First Posted: September 20, 2011
Last Update Posted: August 22, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Array BioPharma
  Purpose
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: None (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 Array BioPharma:

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

Secondary Outcome Measures:
  • Number and nature of Adverse events and clinical activity [ Time Frame: Approximately 3 years ]
  • Pharmacokinetic profile of LGX818 [ Time Frame: Approximately 2 years ]
    LGX818 Plasma concentration

  • Tumor response per RECIST [ Time Frame: Approximately 3 years ]
    This includes duration of response, time to response, progression free survival and overall survival.

  • Baseline molecular status [ Time Frame: Approximately 3 years ]
    Baseline molecular status (mutation/ amplification/ expression) in tumor tissue of potential predictive markers


Enrollment: 107
Study Start Date: September 2011
Estimated Study Completion Date: July 31, 2018
Primary Completion Date: October 2012 (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

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01436656


Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Moffitt SC
Tampa, Florida, United States, 33612
United States, Massachusetts
Massachusetts General Hospital Mass General 2
Boston, Massachusetts, United States, 02114
Australia, New South Wales
Array BioPharma Investigative Site
Westmead, New South Wales, Australia, 2145
Australia, Victoria
Array BioPharma Investigative Site
Parkville, Victoria, Australia, 3050
France
Array BioPharma Investigative Site
Toulouse Cedex 9, France, 31059
Array BioPharma Investigative Site
Villejuif Cedex, France, 94805
Japan
Array BioPharma Investigative Site
Chuo-ku, Tokyo, Japan
Norway
Array BioPharma Investigative Site
Oslo, Norway, NO-0424
Spain
Array BioPharma Investigative Site
Barcelona, Catalunya, Spain, 08035
Array BioPharma Investigative Site
Barcelona, Catalunya, Spain, 08036
Array BioPharma Investigative Site
Madrid, Spain, 28050
Switzerland
Array BioPharma Investigative Site
Chur, Switzerland, 7000
Array BioPharma 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: NCT01436656     History of Changes
Other Study ID Numbers: CLGX818X2101
2011-000556-42 ( EudraCT Number )
First Submitted: April 14, 2011
First Posted: September 20, 2011
Last Update Posted: August 22, 2017
Last Verified: August 2017

Keywords provided by Array BioPharma:
BRAF mutant,
BRAF mutated,
melanoma,
metastatic,
advanced,
RAF kinase inhibitor
BRAF V600 mutation

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