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

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.
 
ClinicalTrials.gov Identifier: NCT01436656
Recruitment Status : Active, not recruiting
First Posted : September 20, 2011
Last Update Posted : May 12, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
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 or disease Intervention/treatment Phase
Melanoma and Metastatic Colorectal Cancer Drug: LGX818 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 66 participants
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
Actual Study Start Date : September 5, 2011
Actual Primary Completion Date : October 1, 2012
Estimated Study Completion Date : July 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma
Drug Information available for: Encorafenib

Arm Intervention/treatment
Experimental: LGX818 - Dose escalation Drug: LGX818
Experimental: LGX818 - Dose Expansion at MTD or RP2D Drug: LGX818



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

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

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

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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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


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
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France
EDOG - Institut Claudius Regaud - PPDS
Toulouse, Haute-garonne, France, 31059 Cedex 9
Institut Gustave Roussy
Villejuif, Val-de-marne, France, 94805
Institut Gustave Roussy
Villejuif, France, 94805
Japan
National Cancer Center Hospital
Chuo-ku, Tokyo, Japan, 104-0045
Spain
Hospital Clinic de Barcelona
Badalona, Spain, 08036
Hospital Universitario Vall d'Hebrón - PPDS
Barcelona, Spain, 08035
Hospital Universitario HM Sanchinarro_CIOCC
Madrid, Spain, 28050
Switzerland
Kantonsspital Graubünden
Chur, Graubünden (DE), Switzerland, 07000
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01436656    
Other Study ID Numbers: CLGX818X2101
C4221010 ( Other Identifier: Alias Study Number )
2011-000556-42 ( EudraCT Number )
First Posted: September 20, 2011    Key Record Dates
Last Update Posted: May 12, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
BRAF mutant,
BRAF mutated,
melanoma,
metastatic,
advanced,
RAF kinase inhibitor
BRAF V600 mutation
Additional relevant MeSH terms:
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Melanoma
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas