Know Cancer

or
forgot password

An Open-Label, Two-Period, Randomized, Crossover Study to Assess the Relative Bioavailability of GSK1120212 Tablet Formulation and the GSK1120212 Pediatric Oral Solution Formulation Following Single-Dose Administration to Adult Subjects With Solid Tumors


Phase 1
18 Years
N/A
Not Enrolling
Both
Cancer

Thank you

Trial Information

An Open-Label, Two-Period, Randomized, Crossover Study to Assess the Relative Bioavailability of GSK1120212 Tablet Formulation and the GSK1120212 Pediatric Oral Solution Formulation Following Single-Dose Administration to Adult Subjects With Solid Tumors


The purpose of this open-label, randomized, 2-treatment, 2-period crossover study with
incomplete washout is to evaluate the relative bioavailability of 2mg GSK1120212 pediatric
oral solution formulation in comparison to 2mg GSK1120212 tablet formulation, to investigate
the safety and tolerability of a single dose of the GSK1120212 pediatric oral solution
formulation as compared to a single dose of the GSK1120212 tablet formulation, and to
investigate the palatability of the GSK1120212 pediatric oral solution formulation.

Subjects will be assigned to one of two possible treatment sequences according to the
randomization code provided to the sites by GSK: a single dose of 2mg GSK1120212 pediatric
oral solution formulation then a single dose of 2mg GSK1120212 tablet formulation, or a
single dose of 2mg GSK1120212 tablet formulation, then a single dose of 2mg GSK1120212
pediatric oral solution formulation. Administration of GSK1120212 in either sequence will
be followed by 7 days of serial blood sampling for pharmacokinetic analysis of plasma
GSK1120212. Safety assessments, including assessment of adverse events, clinical laboratory
values (hematology, clinical chemistry and urinalysis) and vital signs, will be made
throughout the study. After completing the pharmacokinetic assessments for two periods,
eligible subjects may transition to MEK114375, an open-label rollover study of GSK1120212.


Inclusion Criteria:



- Male or female, 18 years of age or older, 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.

- Able to swallow and retain oral medication.

- Histologically- or cytologically-confirmed diagnosis of a solid tumor malignancy that
is not responsive to standard therapies; or for which there is no approved or
curative therapy; or for subjects which refuse standard therapy.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Adequate baseline organ function, defined as: absolute neutrophil count >=
1.2X10^9/L; hemoglobin >=9g/dL; platelets >=75X10^9/L; prothrombin time (PT),
international normalized ratio (INR) and partial thromboplastin time (PTT) <=1.5 X
upper limit of normal (ULN); total bilirubin <=1.5 X ULN; alanine aminotransferase
<=2.5 X ULN; creatinine <=1.5 X ULN OR calculated creatinine clearance or 24-hour
urine creatinine clearance >= 50mL/min; left ventricular ejection fraction (LVEF) >=
lower limit of normal (LLN); systolic blood pressure <140mm Hg

- Women of child-bearing potential must have a negative serum pregnancy test within 14
days of first dose of investigational product administration and agree to use
effective contraception, as defined in the protocol, during the study and for 6 weeks
following the last dose of investigational product.

- Male subjects with female partners of child-bearing potential must agree to use one
of the contraception methods listed in the protocol. This criterion must be followed
from the time of the first dose of study medication until 16 weeks after the last
dose of GSK1120212.

Exclusion criteria

- Currently receiving cancer therapy (e.g., chemotherapy with delayed toxicity,
extensive radiation therapy, immunotherapy, biologic therapy, or major surgery)
within 3 weeks prior to randomization; chemotherapy regimens without delayed toxicity
within 2 weeks prior to randomization; or use of an investigational anti-cancer drug
within 4 weeks prior to randomization.

- Unresolved Grade 2 or greater toxicity (based on NCI-CTCAE, version 4.0, 2009) from
previous anti-cancer therapy except Grade 2 decreased haemoglobin levels or alopecia.

- Pre-existing peripheral neuropathy >= Grade 2.

- Has participated in a clinical trial and received investigational product within 30
days, 5 half-lives or twice the duration of the biological effect of the
investigational product, whichever is longer, prior to the first dose of
investigational product in this study.

- Has participated in a clinical trial that resulted in or made a donation of blood or
blood products in excess of 500mL within 56 days of the first dose of investigational
product in this study.

- Has presence of active GI disease or other condition (e.g., gastrectomy, bariatric
surgery, small or large bowel resection, or cholecystectomy) that may interfere
significantly with absorption of drugs.

- Any serious and/or unstable pre-existing medical (aside from malignancy exception
above), psychiatric disorder, or other conditions that could interfere with subject's
safety, obtaining informed consent or compliance with the study procedures, in the
opinion of the investigator or the GSK medical monitor.

- History of interstitial lung disease or pneumonitis.

- History or current evidence / risk of retinal vein occlusion (RVO) or central serous
retinopathy (CSR), including history of RVO or CSR, or predisposing factors to RVO or
CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic
disease(s) such as hypertension, diabetes mellitus, or history of hyperviscosity or
hypercoagulability syndromes); visible retinal pathology as assessed by ophthalmic
exam that is considered a risk factor for RVO or CSR such as evidence of new optic
disc cupping, evidence of new visual field defects, or intraocular pressure > 21mm
Hg.

- Has symptomatic or untreated leptomeningeal or brain metastases or spinal cord
compression; NOTE: Subjects previously treated for these conditions that have had
stable central nervous system (CNS) disease (verified with consecutive imaging
studies) for >3 months, are asymptomatic and are not currently taking
corticosteroids, or are on stable dose of corticosteroids for at least 1 month prior
to Day 1 of the study are permitted. Subjects are not permitted to receive
enzyme-inducing anti-epileptic drugs (EIAEDs).

- QTcB or QTcF >=480msec.

- Subject has a history or evidence of cardiovascular risk, including any of the
following: history or evidence of current clinically significant uncontrolled
arrhythmias. Exception: subjects with controlled atrial fibrillation for >30days
prior to randomization are eligible OR history of acute coronary syndromes, including
myocardial infarction and unstable angina, coronary angioplasty, or stenting, within
6months prior to randomization.

- History or evidence of current >=Class II congestive heart failure as defined by New
York Heart Association (NYHA).

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label

Outcome Measure:

Evaluate the relative bioavailability of a PfOS formulation relative to the commercial GSK1120212 tablet formulation in adult subjects with solid tumors

Outcome Time Frame:

168 hours X 2

Safety Issue:

No

Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:

GlaxoSmithKline

Authority:

United States: Food and Drug Administration

Study ID:

115892

NCT ID:

NCT01647659

Start Date:

July 2012

Completion Date:

November 2012

Related Keywords:

  • Cancer
  • MEK inhibitor GSK1120212
  • pharmacokinetics
  • powder for oral solution
  • Solid Tumors
  • pediatric formulation

Name

Location

GSK Investigational SitePhoenix, Arizona  85013 - 4496
GSK Investigational SiteGermantown, Tennessee  38138