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An Open-Label, Two-Period, Randomized, Crossover Study to Evaluate the Effect of Food on the Single Dose Pharmacokinetics of the MEK Inhibitor, GSK1120212, in Subjects With Solid Tumors


Phase 1
18 Years
N/A
Not Enrolling
Both
Cancer

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Trial Information

An Open-Label, Two-Period, Randomized, Crossover Study to Evaluate the Effect of Food on the Single Dose Pharmacokinetics of the MEK Inhibitor, GSK1120212, in Subjects With Solid Tumors


open-label, randomized, 2-treatment, 2-period, crossover study with incomplete wash-out to
evaluate the effect of a high-fat, high calorie meal on the single dose PK of GSK1120212 in
subjects with solid tumors. Subjects will be assigned to a fast/fed sequence according to
the randomization code provided to the sites by GSK with subjects randomized to one of 2
possible treatment sequences (Table 1) with each sequence consisting of 2 treatments: a
single 2.0 mg dose of GSK1120212 administered under fasted conditions and a single 2.0 mg
dose of GSK1120212 administered with a high-fat, high-calorie meal


Inclusion Criteria:



- A subject will be eligible for inclusion in this study only if all of the following
criteria apply:

1. Male or female; 18 years of age or older at the time of consent

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

3. Able to swallow and retain oral medication.

4. Histologically or cytologically confirmed diagnosis of a solid tumor.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix
3).

6. Adequate baseline organ function defined in Table 5 Definitions for Adequate
Baseline Organ Function Absolute neutrophil count greater than or equal to 1.2 ×
109/L Hemoglobin greater than or equal to9 g/dL Platelets greater than or equal
to 75 × 109/L Prothrombin time (PT), International normalization ratio (INR)a
and Partial thromboplastin time (PTT) less than or equal to 1.5 times ULN
Hepatic Total bilirubin less than or equal to 1.5 times ULN ALT less than or
equal to 2.5 times ULN Renal Creatinine or less than or equal to 1.5 times ULN
Calculated creatinine clearance or greater than or equal to 50 mL/min 24-hour
urine creatinine clearance greater than or equal to 50 mL/min Cardiac LVEF
greater than or equal to LLNc by ECHO or MUGA

1. INR greater than 1.5 times ULN will be acceptable in case of subjects
receiving therapeutic anticoagulants such as warfarin as long as INR is
monitored during the study according to clinical practice.

2. Calculated by the Cockcroft-Gault formula (see Appendix 2).

3. If LLN is not defined for a given institution, then ejection fraction must
be greater than or equal to 50%.

7. Women of childbearing potential must have a negative serum pregnancy test within
14 days of first dose of study treatment and agree to use effective
contraception, as defined in Section 7.1.1, during the study and for 6 weeks
following the last dose of study treatment.

8. Men with a female partner of childbearing potential must have either had a prior
vasectomy or agree to use effective contraception as described in Section 7.1.2
from the time of the first dose of study treatment until 16 weeks following the
last dose of study treatment (based on the lifecycle of sperm).

Exclusion Criteria:

- A subject will not be eligible for inclusion in this study if any of the following
criteria apply:

1. 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.

2. Has unresolved Grade 2 or greater toxicity (based on NCI-CTCAE, version 4.0)
[NCI Common Terminology Criteria for Adverse Events, 2009] from previous
anti-cancer therapy except Grade 2 decreased hemoglobin levels or alopecia.

3. Has pre-existing peripheral neuropathy of greater than or equal to Grade 2.

4. Has participated in a clinical trial and has received an 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
study treatment in this study.

5. Has participated in a study that resulted in or made a donation of blood or
blood products in excess of 500 mL within 56 days of the first dose of study
treatment.

6. Has presence of active GI disease or other condition (e.g., gastrectomy,
bariatric surgery, small or large bowel resection, or cholecystectomy should be
excluded) that may 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.

7. Has 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 to the study
procedures, in the opinion of the investigator or GSK Medical Monitor.

8. Has a history of interstitial lung disease or pneumonitis.

9. Is currently using a prohibited medication(s) or requires the use of any of the
prohibited medications during the study (see Section 8.2).

• NOTE: Use of anticoagulants such as warfarin is permitted; however, INR must
be monitored in accordance with local institutional practice.

10. Has a history or current evidence/risk of RVO or CSR:

- History of RVO or CSR, or predisposing factors to RVO or CSR (i.e.,
uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease
such as hypertension or 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

- Intraocular pressure greater than 21 mmHg as measured by tonography

11. 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 greater than 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).

12. Has a QtcB or QTcF (preferred) greater than or equal to 480 msec.

13. Has a history or evidence of cardiovascular risk including any of the following:

14. History or evidence of current clinically significant uncontrolled arrhythmias.
Exception: Subjects with controlled atrial fibrillation for greater 30 days
prior to randomization are eligible.

15. History of acute coronary syndromes (including myocardial infarction and
unstable angina), coronary angioplasty, or stenting within 6 months prior to
randomization.

16. History or evidence of current greater than or equal to Class II congestive
heart failure as defined by New York Heart Association (NYHA) (Appendix 4).

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

evaluate the effect of a high-fat, high-calorie meal on the PK of a single dose of GSK1120212 administered to subjects

Outcome Description:

• Area under the plasma concentration-time curve from time zero (pre-dose) to time t (AUC(0-t)), AUC(0-inf), Cmax, and tmax.

Outcome Time Frame:

Predose - 168 hours post dose period 1 and 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:

113709

NCT ID:

NCT01371487

Start Date:

May 2011

Completion Date:

December 2011

Related Keywords:

  • Cancer

Name

Location

GSK Investigational SiteFort Worth, Texas  76104
GSK Investigational SiteRoyal Oak, Michigan  48073
GSK Investigational SiteGermantown, Tennessee  38138