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A Phase II Study of the Selective BRAF Kinase Inhibitor GSK2118436 in Subjects With Advanced Non-small Cell Lung Cancer and BRAF Mutations

Phase 2
18 Years
Open (Enrolling)

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Trial Information

A Phase II Study of the Selective BRAF Kinase Inhibitor GSK2118436 in Subjects With Advanced Non-small Cell Lung Cancer and BRAF Mutations

Inclusion Criteria:

- Signed written informed consent;

- Histologically or cytologically confirmed stage IV non-small cell cancer of the lung

- Documented tumor progression (based on radiological imaging) after receiving at least
one prior approved platinum-based chemotherapy regimen for advanced stage/metastatic

- Measurable disease according to Response Evaluation Criteria in Solid Tumors [RECIST

- At least 18 years of age;

- Anticipated life expectancy of at least three months;

- Presence of a V600E BRAF mutation in lung cancer tissue confirmed in a CLIA-certified
laboratory (or equivalent);

- Able to swallow and retain oral medication;

- Women with child-bearing potential must be willing to practice acceptable methods of
birth control during the study;

- Women of childbearing potential must have a menstrual history inconsistent with
pregnancy and a negative serum pregnancy test within 14 days before the first dose of
study medication and agree to use effective contraception;

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2;

- Must have adequate organ function as defined by the following baseline values:

Absolute neutrophil count (ANC) >/=1.5x109/L Hemoglobin >/=9 g/dL Platelets >/=100x109/L
Serum bilirubin alanine aminotransferase (ALT) creatinine is >1.5 mg/dL, calculate creatinine clearance using standard Cockcroft and
Gault; creatinine clearance must be > 50 mL/min); Prothrombin time /International
normalized ratio (INR) and partial thromboplastin time ejection fraction >/= institutional lower limit of normal

Exclusion Criteria:

- Previous treatment with a BRAF or MEK inhibitor;

- Anti-cancer therapy including chemotherapy, radiation therapy, immunotherapy,
biologic therapy, or major surgery within 14 days prior to start of study therapy;

- Use of any investigational anti-cancer drug within 28 days or 5 half-lives prior to
start of study therapy;

- Current use of a prohibited medication or expected to require any of these
medications during treatment with GSK2118436;

- Unresolved toxicity of National Cancer Institute Common Terminology Criteria for
Adverse Events, version 4.0 (NCI CTCAE v4.0) Grade 2 or higher from previous
anti-cancer therapy, except alopecia;

- Presence of active gastrointestinal disease or other condition that will interfere
significantly with the absorption of drugs;

- Known human immunodeficiency virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C
Virus (HCV) infection. Subjects with evidence of hepatitis B virus clearance may be

- A history of known glucose-6-phosphate dehydrogenase (G6PD) deficiency;

- History of other malignancy; Exception: (a) Subjects who have been successfully
treated and are disease-free for 3 years, (b) a history of completely resected
non-melanoma skin cancer, (c) successfully treated in situ carcinoma, (d) CLL in
stable remission, or (e) indolent prostate cancer requiring no or only anti-hormonal
therapy with histologically confirmed tumor lesions that can be clearly
differentiated from lung cancer target and non-target lesions are eligible

- Subjects with brain metastases are excluded if their brain metastases are:

Symptomatic, or Treated (surgery, radiation therapy) but not clinically and
radiographically stable 3 weeks after local therapy (as assessed by contrast enhanced
MRI), or Asymptomatic and untreated but > 1 cm in the longest dimension

- The following cardiac abnormalities:

Corrected QT (QTc) interval >/= 480 msecs History of acute coronary syndromes (including
unstable angina) within the past 24 weeks Coronary angioplasty, or stenting within the
past 24 weeks Class II, III, or IV heart failure as defined by the New York Heart
Association (NYHA) functional classification system Abnormal cardiac valve morphology (>/=
Grade 2) documented by echocardiogram (subjects with Grade 1 abnormalities [ie, mild
regurgitation/stenosis] can be entered on study). Subjects with moderate valvular
thickening should not be entered on study Known cardiac metastases History of known
arrhythmias (except sinus arrhythmia) within the past 24 weeks

- Uncontrolled medical conditions (i.e., diabetes mellitus, hypertension, etc),
psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol; or unwillingness or inability to follow the procedures
required in the protocol;

- Pregnant, lactating or actively breastfeeding females.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall response rate (ORR) in V600E mutant non-small cell lung cancer subjects, 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

Outcome Time Frame:

Approximately 2 years

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

January 2012

Completion Date:

September 2013

Related Keywords:

  • Cancer
  • dabrafenib
  • GSK2118436
  • BRAF
  • Non-Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



GSK Investigational SiteBakersfield, California  93309
GSK Investigational SiteGainesville, Florida  32610
GSK Investigational SiteSpringfield, Massachusetts  01107
GSK Investigational SiteDuluth, Minnesota  55805
GSK Investigational SiteRaleigh, North Carolina  27609
GSK Investigational SiteBaltimore, Maryland  21201
GSK Investigational SitePittsburgh, Pennsylvania  15213
GSK Investigational SiteGermantown, Tennessee  38138
GSK Investigational SiteNew York, New York  10021
GSK Investigational SiteAurora, Colorado  80012
GSK Investigational SiteSeattle, Washington  98133