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: May 8, 2014
Last verified: May 2014

May 27, 2010
May 8, 2014
August 2010
July 2011   (final data collection date for primary outcome measure)
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.
Overall response rate for the duration that the patient is on study, which is defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR) by investigator assessment as per RECIST 1.1 criteria. [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01153763 on ClinicalTrials.gov Archive Site
  • 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.
  • Progression free survival between the first dose and the earliest date of disease progression or death due to any cause. [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Duration of response for the subset of subjects with confirmed complete response (CR) or partial response (PR) from first documented evidence of CR or PR until time of first documented disease progression or death due to any cause. [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Overall survival from first dose until death due to any cause. [ Time Frame: Approximately 1-2 years. ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of GSK2118436 in BRAF Mutant Metastatic Melanoma
A Phase II (BRF113710) Single-arm, Open-label Study of GSK2118436 in BRAF Mutant Metastatic Melanoma

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.

Not Provided
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Melanoma
Drug: GSK2118436
Subjects will receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.
All patients
Subjects will receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.
Intervention: Drug: GSK2118436
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
92
February 2016
July 2011   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   France,   Germany,   Italy
 
NCT01153763
113710
Yes
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP