Last updated: 11/03/2018 15:33:40
A study of GSK2118436 in BRAF mutant metastatic melanoma
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A Phase II (BRF113710) single-arm, open-label study of GSK2118436 in BRAF mutant metastatic melanoma
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:
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
Timeframe: Up to 60 months
Secondary outcomes:
Number of participants with a best overall response of CR or PR as assessed by the investigator and an independent reviewer for participants who had a BRAF V600K mutation
Timeframe: Up to 60 months
Progression-free Survival (PFS) as assessed by the investigator and an independent reviewer for participants who had a BRAF V600E mutation
Timeframe: Up to 60 months
Progression-free Survival (PFS) as assessed by the investigator and an independent reviewer for participants who had a BRAF V600K mutation
Timeframe: Up to 60 months
Duration of response as assessed by the investigator and an independent reviewer for participants who had a BRAF V600E mutation
Timeframe: Up to 60 months
Duration of response as assessed by the investigator and an independent reviewer for participants who had a BRAF V600K mutation
Timeframe: Up to 60 months
Overall survival for participants who had a BRAF V600E mutation
Timeframe: Up to 60 months
Overall survival for participants who had a BRAF V600K mutation
Timeframe: From the first dose to death due to any cause (up to 60 months)
Number of participants with AEs and Serious Adverse Events (SAEs)
Timeframe: Up to 60 months
Number of participants with change from Baseline in clinical chemistry and hematology toxicity grades
Timeframe: Up to 60 months
Number of participants with change from Baseline in temperature and pulse rate
Timeframe: Up to 60 months
Number of participants with increase from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP)
Timeframe: Up to 60 months
Number of participants with change from Baseline in Left Ventricular Ejection Fraction (LVEF) levels
Timeframe: Up to 60 months
Interventions:
Drug: GSK2118436
Enrollment:
92
Observational study model:
Not applicable
Primary completion date:
2011-07-07
Time perspective:
Not applicable
Clinical publications:
PA Ascierto, D Minor, A Ribas, C Lebbe, A Siegfried, N Arya, M Guckert, D Schadendorf, R Kefford, J-J Grob, O Hamid, R Amaravadi, E Simeone, T Wilhelm, KB Kim, G Long,A-M Martin, J Mazumdar, V Goodman, U Trefzer . A Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol. 2013;
Daniele Ouellet, Ekaterina Gibiansky, Cathrine L Denton, Anne O’Hagan, Pat Haney, Julie Switzky, Vicki Goodman.Population Pharmacokinetics of Dabrafenib: Effect of Dose, Time, Covariates and Relationship with its Metabolites .J Clin Pharmacol.2014;54(6):696-706
PA Ascierto, D Minor, A Ribas, C Lebbe, A Siegfried, N Arya, M Guckert, D Schadendorf, R Kefford, J-J Grob, O Hamid, R Amaravadi, E Simeone, T Wilhelm, KB Kim, G Long,A-M Martin, J Mazumdar, V Goodman, U Trefzer .A Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma.J Clin Oncol.2013;31(26):3205-3211
Medical condition
Melanoma
Product
dabrafenib
Collaborators
Not applicable
Study date(s)
August 2010 to April 2016
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 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.
- 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.
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Newcastle, New South Wales, Australia, 2300
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
Status
Study Complete
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37232
Status
Study Complete
Location
GSK Investigational Site
Los Angeles, California, United States, 90095
Status
Study Complete
Location
GSK Investigational Site
Kiel, Schleswig-Holstein, Germany, 24105
Status
Study Complete
Location
GSK Investigational Site
Westmead, New South Wales, Australia, 2145
Status
Study Complete
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45122
Status
Study Complete
Location
GSK Investigational Site
Houston, Texas, United States, 77030-4009
Status
Study Complete
Location
GSK Investigational Site
Los Angeles, California, United States, 90025
Status
Study Complete
Location
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Status
Study Complete
Location
GSK Investigational Site
San Francisco, California, United States, 94115
Status
Study Complete
Location
GSK Investigational Site
Luebeck, Schleswig-Holstein, Germany, 23538
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2011-07-07
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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