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Determination of the Absolute Bioavailability of GSK2118436 Following a Single Oral Dose Co-Administered With an Intravenous Radiolabelled Microtracer of GSK2118436 in Subjects With BRAF Mutant Solid Tumors

Phase 1
18 Years
Not Enrolling

Thank you

Trial Information

Determination of the Absolute Bioavailability of GSK2118436 Following a Single Oral Dose Co-Administered With an Intravenous Radiolabelled Microtracer of GSK2118436 in Subjects With BRAF Mutant Solid Tumors

Inclusion Criteria:

- Male or female at least 18 years of age at the time of signing the informed consent

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form;

- Body weight >/= 45 kg and a body mass index >/= 19 kg/m2 and (inclusive);

- Able to swallow and retain oral medication;

- BRAF mutation-positive tumor as determined via relevant genetic testing;

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

- Women of child-bearing potential and men with reproductive potential must be willing
to practice acceptable methods of birth control. Additionally, women of childbearing
potential must have a negative serum pregnancy test within 14 days prior to the first
dose of study treatment;

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

ANC >/=1.2 x 109/L Hemoglobin >/=9 g/dL Platelets >/=100 x 109/L Serum bilirubin upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) calculated creatinine clearance >/= 60 mL/min Prothrombin time / INR and partial
thromboplastin time /= institutional
lower limit of normal by ECHO

Exclusion Criteria:

- Currently receiving cancer therapy (e.g., chemotherapy with delayed toxicity,
extensive radiation therapy, immunotherapy, biologic therapy) within the last 3
weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks; or use
of an investigational anti-cancer drug within 28 days preceding the first dose of
GSK2118436; use of any other investigational product within 30 days, 5 half-lives or
twice the duration of the biological effect of the investigational product (whichever
is warranted by data);

- Has participated in a 14C human research study in the 12 months prior to
administration of study medication;

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

- Consumption of red wine, Seville oranges, grapefruit or grapefruit juice from 7 days
prior to the first dose of study medication;

- Current use of therapeutic warfarin (note: low molecular weight heparin and
prophylactic low-dose warfarin are permitted);

- History of sensitivity to heparin or heparin-induced thrombocytopenia;

- Any major surgery within the last 4 weeks;

- Unresolved toxicity greater than National Cancer Institute Common Terminology
Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0) [NCI, 2009] Grade 2 from
previous anti-cancer therapy except alopecia;

- Presence of active gastrointestinal disease or other condition (e.g., small bowel or
large bowel resection) that will interfere significantly with the absorption of
drugs. If clarification is needed as to whether a condition will significantly
affect absorption of drugs, contact the GSK medical monitor for permission to enrol
the subject;

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

- Presence of invasive malignancy other than one of the malignancies covered under
Inclusion Criterion; subjects with a history of another malignancy that has been
definitively treated can be enrolled;

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

Symptomatic Treated (surgery, radiation therapy), but not clinically and radiographically
stable for a period of at least one month prior to study entry, or Asymptomatic and
untreated but > 1 cm in the longest dimension Exception: Subjects with small (≤ 1 cm in
the longest dimension), asymptomatic brain metastases that do not need immediate local
therapy can be enrolled. Subjects on a stable dose of corticosteroids for more than one
month, or those who have been off corticosteroids for at least 2 weeks can be enrolled.
Subjects must also be off of enzyme-inducing anticonvulsants for more than 4 weeks;

- Corrected QT (QTc) interval >/= 480 msecs;

- History of acute coronary syndromes (including unstable angina), 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 documented
by ECHO [subjects with minimal abnormalities (i.e., mild regurgitation/stenosis) can
be entered on study - if clarification is needed as to whether an ECHO abnormality is
minimal, please contact the GSK medical monitor); or history of known cardiac
arrhythmias (except sinus arrythmias) within the past 24 weeks;

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to the study drugs, or excipients (note: to date there are no
known drugs chemically related to GSK2118436 which are approved by the FDA);

- Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension),
psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol; or history of alcohol or drug abuse within 6 months
prior to screening; or unwillingness or inability to follow the procedures required
in the protocol;

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

- Donation of blood or blood products in excess of 500 mL within the 56 days prior to
administration of study medication;

- Pregnant females as determined by positive β hCG test at screening or prior to dosing
or lactating females who are actively breast feeding;

- Subject is mentally or legally incapacitated;

Type of Study:


Study Design:

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

Outcome Measure:

The percent of absolute bioavailability (F) of GSK2118436 following single-dose oral HPMC capsule and a concomitant IV microdose

Outcome Time Frame:

Up to 72 hours

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

June 2011

Completion Date:

September 2011

Related Keywords:

  • Cancer
  • GSK2118436
  • BRAF inhibitor
  • BRAF-mutation positive tumor
  • Oncology
  • absolute bioavailability
  • microtracer



GSK Investigational SiteSeattle, Washington  98133