Study to Investigate the Absorption, Distribution, Metabolism and Elimination of [14C]GSK1120212

NCT ID: NCT01387204

Last Updated: 2017-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-02-15

Study Completion Date

2011-07-18

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

GSK1120212 is a reversible and highly selective allosteric inhibitor of MEK1 and MEK2 activation and kinase activity currently being developed for the treatment of malignant melanoma. This is a Phase I, open-label, non-randomized, single-dose study designed to characterize the absorption, distribution, metabolism, and elimination (ADME) of a single oral dose of MEK inhibitor \[14C\]GSK1120212 as a solution in male subjects with solid tumor malignancies. A sufficient number of subjects will be enrolled to complete approximately four evaluable subjects. Following completion of the study, subjects may elect to continue dosing with GSK1120212 in the rollover study, MEK114375.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cancer

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

MEK inhibitor elimination Phase 1 GSK1120212 cancer Pharmacokinetics oncology radiolabeled ADME

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Single-Dose, 2 mg [14C]GSK1120212

A single 2 mg (2 mg/10mL) oral dose of \[14C\]GSK1120212 containing approximately 79 μCi of radioactivity will be delivered as a solution.

Group Type EXPERIMENTAL

GSK1120212

Intervention Type DRUG

The 2 mg dose is based on clinical data from the ongoing FTIH study in which subjects have been dosed daily for greater than 21 days, as well as preclinical toxicity data.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

GSK1120212

The 2 mg dose is based on clinical data from the ongoing FTIH study in which subjects have been dosed daily for greater than 21 days, as well as preclinical toxicity data.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Male 18 years old or older.
2. Written informed consent provided
3. Body weight greater than or equal to 45 kg and a BMI greater than or equal to 19 kg/m2 and less than or equal to 35 kg/m2 (inclusive).
4. Able to swallow and retain oral medication.
5. Histologically or cytologically confirmed diagnosis of a solid tumor.
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
7. Agree to use one of the contraception methods listed in the protocol from the time of the first dose of study medication until sixteen weeks after the last dose of study medication.
8. A history of regular bowel movements (approximately once per day).
9. Adequate baseline organ function as listed in the protocol.

Exclusion Criteria

1. Currently receiving cancer therapy as specified in the protocol.
2. Serious and/or unstable pre-existing medical psychiatric disorder, or other conditions.
3. Any major surgery within the last four weeks.
4. Unresolved toxicity equal to or greater than Grade 2 from previous anti-cancer therapy except alopecia.
5. An occupation within the past 12 months which requires monitoring for radiation exposure, nuclear medicine procedures or excessive x-rays.
6. Radiation exposure from the previous three year period over 10 mSv if exposed to ionizing radiation above background as a result of work with radiation as category A (classified) workers or as a result of research studies.
7. History of interstitial lung disease or pneumonitis.
8. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to dimethyl sulfoxide (DMSO).
9. Current use of a prohibited medications described in the protocol.

• Use of anticoagulants such as warfarin is permitted.
10. History RVO or CSR.

* Predisposing factors to RVO or CSR.
* Visible retinal pathology that is considered a risk factor for RVO or CSR such as:

\- Evidence of new optic disc cupping

\- Intraocular pressure greater than 21 mm Hg as measured by tonography. 11.1. Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. (Previously treated and have had stable CNS disease for greater than 3 months, asymptomatic and off corticosteroids, or on stable dose of corticosteroids for at least 1 month prior to study Day 1 are permitted).

11.2. Receiving enzyme inducing anti-epileptic drugs (EIAEDs). 12. History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 6 months. 13. QTcB greater than or equal to 480 msec. 14. History or evidence of current clinically significant uncontrolled arrhythmias.

15\. History or evidence of current greater than or equal to Class II congestive heart failure.

16\. Active gastrointestinal disease or other condition (e.g., gastrectomy, bariatric surgery, small bowel or large bowel resection, or cholecystectomy).

17\. A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus, or Hepatitis C Virus.

18\. Alcohol or drug abuse within six months prior to screening. 19. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs or excipients.

20\. Participated in a clinical trial and has received an investigational product within 30 days or five half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) before the 1st dose.

21\. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

22\. Mentally or legally incapacitated.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

GSK Investigational Site

Tacoma, Washington, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Allen LF, Sebolt-Leopold J, Meyer MB. CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK). Semin Oncol. 2003 Oct;30(5 Suppl 16):105-16. doi: 10.1053/j.seminoncol.2003.08.012.

Reference Type BACKGROUND
PMID: 14613031 (View on PubMed)

Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA. Mutations of the BRAF gene in human cancer. Nature. 2002 Jun 27;417(6892):949-54. doi: 10.1038/nature00766. Epub 2002 Jun 9.

Reference Type BACKGROUND
PMID: 12068308 (View on PubMed)

GlaxoSmithKline Document Number HM2009/00151/01 GSK1120212 Investigator's Brochure Report Date 4 June 2010.

Reference Type BACKGROUND

GlaxoSmithKline Document Number RD2009/01379/00. Dosimetry Review for oral [14C]GSK1120212. Report Date 19-Nov-2009.

Reference Type BACKGROUND

GlaxoSmithKline Document Number RM2007/00642/03. MEK111054: An open-label, multiple-dose, dose escalation study to investigate the safety, harmacokinetics, and pharmacodynamics of the MEK inhibitor GSK1120212 in subjects with solid tumors or lymphoma. 2009.

Reference Type BACKGROUND

Lorusso PM, Adjei AA, Varterasian M, Gadgeel S, Reid J, Mitchell DY, Hanson L, DeLuca P, Bruzek L, Piens J, Asbury P, Van Becelaere K, Herrera R, Sebolt-Leopold J, Meyer MB. Phase I and pharmacodynamic study of the oral MEK inhibitor CI-1040 in patients with advanced malignancies. J Clin Oncol. 2005 Aug 10;23(23):5281-93. doi: 10.1200/JCO.2005.14.415. Epub 2005 Jul 11.

Reference Type BACKGROUND
PMID: 16009947 (View on PubMed)

LoRusso PM, Krishnamurthi S, Rinehart JR, et al. A Phase 1-2 clinical study of the second-generation MEK inhibitor, PD 0325901 in patients with advanced cancer. J Clin Oncol. 2005; 23:3011.

Reference Type BACKGROUND

LoRusso PM, Krishnamurthi SS, Rinehart JJ, Nabell LM, Croghan GA, Chapman PB, Selaru P, Kim S, Ricart AD, Wilner KD. Clinical aspects of a phase I study of PD-0325901, a selective oral MEK inhibitor, in patients with advanced cancer. Presented at AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2007; 6:3649s [abstr B113].

Reference Type BACKGROUND

NCI. Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. DHHS,NCI, NIH, Bethesda, MD; 2009.

Reference Type BACKGROUND

Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.

Reference Type BACKGROUND
PMID: 7165009 (View on PubMed)

Tzekova, V, Cebotaru C, Ciuleanu TE, et al. Efficacy and safety of AZD6244 (ARRY-142886) as second/third-line treatment of patients (pts) with advanced non-small cell lung cancer (NSCLC). J Clin Oncol. 2008; 26:431s.

Reference Type BACKGROUND

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

113708

Identifier Type: -

Identifier Source: org_study_id