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Phase I/IIa, 2-Part, Multi-Center, Single-Arm, Open-Label Study to Determine the Safety, Tolerability and Pharmacokinetics of Oral Dabrafenib in Pediatric Subjects Aged 1 Month to <18 Years With Advanced BRAF V600-Mutation Positive Solid Tumors

Phase 1
1 Month
17 Years
Open (Enrolling)
Neoplasms, Brain

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Trial Information

Phase I/IIa, 2-Part, Multi-Center, Single-Arm, Open-Label Study to Determine the Safety, Tolerability and Pharmacokinetics of Oral Dabrafenib in Pediatric Subjects Aged 1 Month to <18 Years With Advanced BRAF V600-Mutation Positive Solid Tumors

Inclusion Criteria:

- Written informed consent - a signed informed consent and/or assent (as age
appropriate) will be obtained according to institutional guidelines

- Male or female between one month and <18 years of age (inclusive) at the time of
signing the informed consent form

- Recurrent disease or progressive disease after having received at least one standard
therapy for their disease

- At least one evaluable lesion

- BRAF V600 mutation-positive tumor as confirmed in a Clinical Laboratory Improvement
Amendments (CLIA)-approved laboratory or equivalent

- Performance score of >=50% according to the Karnofsky/Lansky performance status scale
(subjects with a performance status of <=50% can be enrolled if the subject's
confinement to bed and inability to carry out activities is due solely to
cancer-related pain, as assessed by the investigator)

- Females of child-bearing potential (with negative serum pregnancy test within 7 days
prior to the first dose of study medication) and males with reproductive potential
must be willing to practice acceptable methods of birth control.

- Must have adequate organ function as defined by the following values: Adequate bone
marrow function defined as-absolute neutrophil count (ANC) >=1000/ microliter (µL),
hemoglobin >=8.0 grams (g)/ deciliter (dL) (may receive red blood cell transfusions),
platelets >=75,000/µL (transfusion independent, defined as not receiving platelet
transfusions within a 7 day period prior to enrollment; adequate renal and metabolic
function defined as: calculated creatinine clearance (Cockcroft-Gault), calculated
glomerular filtration rate (GFR) (revised Schwartz formula), or radioisotope GFR >=60
milliliters/minutes (mL/min)/1.73 meter square (m^2); or a serum creatinine within
the institutional reference range upper limit of normal (for age/gender, if
available); adequate liver function defined as: bilirubin (sum of conjugated +
unconjugated) <=1.5 x upper limit of normal (ULN) for age, aspartate
aminotransaminase (AST) and alanine transaminase (ALT) <=2.5 x ULN; AST/ALT may be <5
x ULN at baseline if liver metastases are present (requires radiographic confirmation
of liver metastases) and adequate cardiac function defined as: left ventricular
ejection fraction (LVEF) of either >=50% by ECHO or greater than institutional lower
limit of normal (LLN) by echocardiogram (ECHO) (while not receiving medications for
cardiac function), corrected QT using Bazett's (QTcB) interval <450 milliseconds

Exclusion Criteria:

- Part 2 ONLY: Previous treatment with dabrafenib, another RAF inhibitor, or a
mitogen-activated protein kinase (MEK) inhibitor (exception: prior treatment with
sorafenib is permitted)

- Malignancy OTHER than the BRAF mutant malignancy under study

- Had chemotherapy or radiotherapy within 3 weeks (or 6 weeks for nitrosoureas or
mitomycin C) prior to administration of the first dose of study treatment

- The subject has received an investigational product within the following time period
prior to the first dosing day in the current study: 28 days or 5 half-lives or twice
the duration of the biological effect of the investigational product (whichever is
warranted by the data)

- History of another 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 (definition: clinical stage T1 or T2a, Gleason score <=6, and
prostate specific antigen [PSA] <10 nanograms (ng)/mL) requiring no or only
anti-hormonal therapy with histologically confirmed tumour lesions that can be
clearly differentiated from lung cancer target and non-target lesions are eligible

- Current use of a prohibited medication or herbal preparation or requires any of these
medications during the study

- Unresolved toxicity greater than National Cancer Institute Common Terminology
Criteria for Adverse Events (NCI CTCAE) v4.0 Grade 2 or higher from previous
anti-cancer therapy except those that in the opinion of the investigator are not
clinically relevant given the known safety/toxicity profile of dabrafenib (e.g.,
alopecia and/or peripheral neuropathy related to platinum or vinca alkaloid based

- Has leukaemia

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to dabrafenib and its excipients.

- Autologous or allogeneic stem cell transplant within 3 months prior to enrolment

- History of myocardial infarction, severe or unstable angina, peripheral vascular
disease or familial QTc prolongation

- Subjects with abnormal cardiac valve morphology (>=grade 2) documented by
echocardiogram, moderate valvular thickening.

- Subjects with known glucose-6-phosphate dehydrogenase (G6PD) deficiency

- Known, uncontrolled cardiac arrhythmias (except sinus arrhythmia) within the past 24

- Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension, liver disease
or uncontrolled infection), 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

- Presence of active GI disease or other condition (e.g., small bowel or large bowel
resection) that will interfere significantly with the absorption of drugs.

- A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus, or
Hepatitis C Virus infection (subjects with laboratory evidence of Hepatitis B Virus
clearance may be enrolled)

- Pregnant females as determined by positive human chorionic gonadotropin (hCG) test at
screening or prior to dosing and lactating females who are actively breast feeding.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and tolerability of dabrafenib as assessed by number of subjects with adverse events (AE)s

Outcome Description:

Safety and tolerability parameters will include recording of AEs, in Part 1 and Part 2 of the study.

Outcome Time Frame:

Through Week 57 in Part 1 and Part 2

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

February 2013

Completion Date:

January 2015

Related Keywords:

  • Neoplasms, Brain
  • BRAF
  • dabrafenib
  • dose escalation
  • V600-mutation positive
  • pediatrics
  • Brain Neoplasms
  • Neoplasms



GSK Investigational Site Springfield, Massachusetts  01107
GSK Investigational Site Akron, Ohio  44304
GSK Investigational Site Baltimore, Maryland  21201
GSK Investigational Site New York, New York  10021