A Study of GSK2118436 in BRAF Mutant Metastatic Melanoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01153763
First received: May 27, 2010
Last updated: August 14, 2014
Last verified: May 2014
  Purpose

BRF113710 is a Phase II, single-arm, open-label study to assess the efficacy, safety, and tolerability of GSK2118436 administered twice daily as a single agent in subjects with BRAF mutant metastatic melanoma. Subjects will receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.


Condition Intervention Phase
Melanoma
Drug: GSK2118436
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II (BRF113710) Single-arm, Open-label Study of GSK2118436 in BRAF Mutant Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator for Participants Who Had a BRAF V600E Mutation [ Time Frame: From the first dose of study medication to the first documented evidence of a confirmed complete response or partial response (up to 26.9 weeks) ] [ Designated as safety issue: No ]
    A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]). To be assigned a status of PR or CR, a confirmatory disease assessment was required at Week 12 if an initial response was seen at the Week 6 scan. Initial responses (CR/PR) that occured at Week 12 or later were required to be confirmed not less than 4 weeks and not more than 6 weeks after the criteria for response were first met. Response was determined by investigator assessment as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.


Secondary Outcome Measures:
  • Number of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation [ Time Frame: From the first dose of study medication until the first documented evidence of a confirmed complete response or partial response (up to 11 weeks) ] [ Designated as safety issue: No ]
    A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]). To be assigned a status of PR or CR, a confirmatory disease assessment had to have been performed at Week 12 if an initial response was seen at the Week 6 scan. Initial responses (CR/PR) that occured at Week 12 or later should have been confirmed not less than 4 weeks and not more than 6 weeks after the criteria for response were first met. Response was evaluated by an investigator as per RECIST, version 1.1.

  • Progression-free Survival (PFS) as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600E Mutation [ Time Frame: From the first dose of study medication to the earliest date of disease progression or death due to any cause (up to 9.9 months) ] [ Designated as safety issue: No ]
    PFS is defined as the interval between the first dose of study medication and the earliest date of disease progression (PD) or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the investigator/independent reviewer according to RECIST, version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). For participants who received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS was censored at the last adequate assessment. For participants who did not have a documented date of progression or death, PFS was censored at the date of last adequate assessment.

  • Progression-free Survival (PFS) as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation [ Time Frame: From the first dose of study medication to the earliest date of disease progression or death due to any cause (up to 9.9 months) ] [ Designated as safety issue: No ]
    PFS is defined as the interval between the first dose of study medication and the earliest date of disease progression (PD) or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the investigator/independent reviewer according to RECIST, version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). For participants who did not die, PFS was censored at the date of last contact.

  • Duration of Response as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600E Mutation [ Time Frame: From the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 31.3 weeks) ] [ Designated as safety issue: No ]
    Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]) is defined as the time from the first documented evidence of a PR or CR until the first documented sign of disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. For participants who did not die, duration of response was censored at the date of last contact.

  • Duration of Response as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation [ Time Frame: From the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 29.6 weeks) ] [ Designated as safety issue: No ]
    Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]) is defined as the time from the first documented evidence of a PR or CR until the first documented sign of disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. For participants who did not die or progress, duration of response was censored at the date of last contact.

  • Overall Survival for Participants Who Had a BRAF V600E Mutation [ Time Frame: From the first dose of study medication to death due to any cause (up to 9.9 months) ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from the first dose of study medication until death due to any cause. For participants who did not die, overall survival was censored at the date of last contact.

  • Overall Survival for Participants Who Had a BRAF V600K Mutation [ Time Frame: From the first dose to death due to any cause (up to 9.9 months) ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from the first dose of study medication until death due to any cause. For participants who did not die, overall survival was censored at the date of last contact.


Enrollment: 92
Study Start Date: August 2010
Estimated Study Completion Date: February 2016
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
All patients
Subjects will receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.
Drug: GSK2118436
Subjects will receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.

  Eligibility

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

Inclusion Criteria:

  • Must be at least 18 years of age
  • Must have histologically confirmed cutaneous metastatic melanoma (Stage IV) that is BRAF mutation-positive (V600 E/K) as determined via central testing with a BRAF mutation assay.
  • Is treatment naive or has received prior treatment for metastatic melanoma.
  • Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
  • Women of child-bearing potential must have a negative pregnancy test within 14 days prior to the first dose of study treatment.
  • Women with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 4 weeks after the last dose of study medication.
  • Men with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 16 weeks after the last dose of study medication.
  • Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  • Adequate organ function.

Exclusion Criteria:

  • Previous treatment with a BRAF or MEK inhibitor.
  • Cancer therapy (chemotherapy with delayed toxicity, radiation therapy, immunotherapy, biologic therapy, or major surgery) within the last 3 weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks; or use of any investigational anti-cancer or other drug within 28 days or 5 half-lives, whichever is longer, preceding the first dose of GSK2118436.
  • A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection.
  • History or evidence of brain metastases on MRI or head CT if MRI is not able to be performed.
  • History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
  • Certain cardiac abnormalities.
  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: NCT01153763

Locations
United States, California
GSK Investigational Site
Los Angeles, California, United States, 90025
GSK Investigational Site
Los Angeles, California, United States, 90095
GSK Investigational Site
San Francisco, California, United States, 94115
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37232
United States, Texas
GSK Investigational Site
Houston, Texas, United States, 77030-4009
Australia, New South Wales
GSK Investigational Site
Newcastle, New South Wales, Australia, 2300
GSK Investigational Site
Westmead, New South Wales, Australia, 2145
Australia, Western Australia
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
France
GSK Investigational Site
Bordeaux, France, 33075
GSK Investigational Site
Boulogne-Billancourt, France, 92100
GSK Investigational Site
Lille, France, 59037
GSK Investigational Site
Marseille Cedex 5, France, 13385
GSK Investigational Site
Montpellier, France, 34295
GSK Investigational Site
Paris Cedex 10, France, 75475
GSK Investigational Site
Villejuif, France, 94805
Germany
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45122
GSK Investigational Site
Kiel, Schleswig-Holstein, Germany, 24105
GSK Investigational Site
Luebeck, Schleswig-Holstein, Germany, 23538
GSK Investigational Site
Berlin, Germany, 10117
Italy
GSK Investigational Site
Napoli, Campania, Italy, 80131
GSK Investigational Site
Genova, Liguria, Italy, 16132
GSK Investigational Site
Padova, Veneto, Italy, 35128
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01153763     History of Changes
Other Study ID Numbers: 113710
Study First Received: May 27, 2010
Results First Received: June 12, 2013
Last Updated: August 14, 2014
Health Authority: Italy: Agenzia Italiana del Farmaco
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
France: Agence Française de Sécurité Sanitaire des Produits de Santé
United States: Food and Drug Administration
Australia: Therapeutic Goods Administration

Keywords provided by GlaxoSmithKline:
Metastatic melanoma
BRAF mutant
Melanoma
BRAF mutant metastatic melanoma

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
Dabrafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014