CancerPhase 1NCT01387204
Study to Investigate the Absorption, Distribution, Metabolism and Elimination of [14C]GSK1120212
A Phase 1 study testing GSK1120212 in people with Cancer, run by GlaxoSmithKline at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Cancer
- What is being tested?
- GSK1120212
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2011to 18 Jul 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male 18 years old or older.
- Written informed consent provided
- 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).
- Able to swallow and retain oral medication.
- Histologically or cytologically confirmed diagnosis of a solid tumor.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
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- 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.
- A history of regular bowel movements (approximately once per day).
- Adequate baseline organ function as listed in the protocol.
Who cannot join
- Currently receiving cancer therapy as specified in the protocol.
- Serious and/or unstable pre-existing medical psychiatric disorder, or other conditions.
- Any major surgery within the last four weeks.
- Unresolved toxicity equal to or greater than Grade 2 from previous anti-cancer therapy except alopecia.
- An occupation within the past 12 months which requires monitoring for radiation exposure, nuclear medicine procedures or excessive x-rays.
- 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.
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- History of interstitial lung disease or pneumonitis.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to dimethyl sulfoxide (DMSO).
- Current use of a prohibited medications described in the protocol.
- Use of anticoagulants such as warfarin is permitted.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label Mass Balance Study to Investigate the Absorption, Distribution, Metabolism and Elimination of a Single Oral Dose of MEK Inhibitor [14C]GSK1120212 in Male Subjects With Solid Tumors
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.
- Conditions
- Cancer
- Being tested
- GSK1120212
- Keywords
- MEK inhibitor, elimination, Phase 1, GSK1120212, cancer, Pharmacokinetics, oncology, radiolabeled ADME
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1120212Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Single-Dose, 2 mg [14C]GSK1120212 | Experimental | A single 2 mg (2 mg/10mL) oral dose of [14C]GSK1120212 containing approximately 79 μCi of radioactivity will be delivered as a solution. Receives: Drug: GSK1120212 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total excretion of radioactivity
- Total and relative excretion of radioactivity in urine and feces following a single, 2 mg oral solution dose of [14C]GSK1120212
Measured: 11 days
Secondary outcomes (9)
Total radioactivity concentration in blood and plasma
AUC(0- t), AUC(0-∞), Cmax, tmax and t1/2
Measured: 11 days
Characterize and quantify metabolites in urine plasma and feces
Characterize and quantify metabolites of GSK1120212 in plasma, urine and feces (studied separately under a DMPK protocol).
Measured: 11 days
Assess covalent binding of drug related material to plasma proteins
Assess percentage of drug-related material that covalently bonds to plasma proteins (studied separately under a DMPK protocol)
Measured: 11 days
Blood:plasma ratio
Blood:plasma ratio of total drug-related material (radioactivity)
Measured: 11 days
Pharmacokentic concentrations in plasma
Plasma GSK1120212 concentrations AUC(0-t), AUC(0-∞), Cmax, tmax, and t1/2
Measured: 11 days
AEs
Number of adverse events (AEs)
Measured: From dosing on Day 1 to Follow-up
Vital signs
Changes from baseline
Measured: Screening, Day -1, Day 1, Day 5, and Follow-up
ECGs
Changes from baseline
Measured: Screening, Day 1 pre-dose, 24 hours, Day 11 and Follow-up
Clinical Laboratory assessments
Changes from baslines
Measured: Screening, Day -1, and Day 11
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2011 (estimated)
- Study start15 Feb 2011
- Primary completion18 Jul 2011
- Study completion18 Jul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01387204
- Sponsor's protocol ID
- 113708
- Status last verified
- Nov 2017
- First submitted
- 9 Jun 2011
- Last updated
- 13 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 14613031Davies 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.
PubMed 12068308GlaxoSmithKline Document Number HM2009/00151/01 GSK1120212 Investigator's Brochure Report Date 4 June 2010.
GlaxoSmithKline Document Number RD2009/01379/00. Dosimetry Review for oral [14C]GSK1120212. Report Date 19-Nov-2009.
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.
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.
PubMed 16009947LoRusso 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.
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].
NCI. Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. DHHS,NCI, NIH, Bethesda, MD; 2009.
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.
PubMed 7165009Tzekova, 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.
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Mass Balance Study to Investigate the Absorption, Distribution, Metabolism and Elimination of a Single Oral Dose of MEK Inhibitor [14C]GSK1120212 in Male Subjects With Solid Tumors
- ClinicalTrials.gov ID
- NCT01387204
- Acronym / sponsor ID
- 113708
- Conditions
- Cancer
- Keywords
- MEK inhibitor, elimination, Phase 1, GSK1120212, cancer, Pharmacokinetics, oncology, radiolabeled ADME
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 15 Feb 2011 (actual)
- Primary completion
- 18 Jul 2011 (actual)
- Study completion
- 18 Jul 2011 (actual)
- First posted
- 4 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single-Dose, 2 mg [14C]GSK1120212 | Experimental | Drug: GSK1120212A single 2 mg (2 mg/10mL) oral dose of [14C]GSK1120212 containing approximately 79 μCi of radioactivity will be delivered as a solution. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male 18 years old or older.
- Written informed consent provided
- 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).
- Able to swallow and retain oral medication.
- Histologically or cytologically confirmed diagnosis of a solid tumor.
Key exclusion criteria (23 listed)
- Currently receiving cancer therapy as specified in the protocol.
- Serious and/or unstable pre-existing medical psychiatric disorder, or other conditions.
- Any major surgery within the last four weeks.
- Unresolved toxicity equal to or greater than Grade 2 from previous anti-cancer therapy except alopecia.
- An occupation within the past 12 months which requires monitoring for radiation exposure, nuclear medicine procedures or excessive x-rays.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK1120212The 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. | Drug | Single-Dose, 2 mg [14C]GSK1120212 |
Primary outcome
Total excretion of radioactivity
Time frame: 11 days
• Total and relative excretion of radioactivity in urine and feces following a single, 2 mg oral solution dose of [14C]GSK1120212
9 secondary outcomes
Total radioactivity concentration in blood and plasma
Time frame: 11 days
Characterize and quantify metabolites in urine plasma and feces
Time frame: 11 days
Assess covalent binding of drug related material to plasma proteins
Time frame: 11 days
Blood:plasma ratio
Time frame: 11 days
Pharmacokentic concentrations in plasma
Time frame: 11 days
AEs
Time frame: From dosing on Day 1 to Follow-up
Vital signs
Time frame: Screening, Day -1, Day 1, Day 5, and Follow-up
ECGs
Time frame: Screening, Day 1 pre-dose, 24 hours, Day 11 and Follow-up
Clinical Laboratory assessments
Time frame: Screening, Day -1, and Day 11
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2017.
- Background: PubMed 14613031Allen 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.
- Background: PubMed 12068308Davies 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.
- BackgroundGlaxoSmithKline Document Number HM2009/00151/01 GSK1120212 Investigator's Brochure Report Date 4 June 2010.
- BackgroundGlaxoSmithKline Document Number RD2009/01379/00. Dosimetry Review for oral [14C]GSK1120212. Report Date 19-Nov-2009.
- BackgroundGlaxoSmithKline 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.
- Background: PubMed 16009947Lorusso 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.
- BackgroundLoRusso 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.
- BackgroundLoRusso 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].
- BackgroundNCI. Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. DHHS,NCI, NIH, Bethesda, MD; 2009.
- Background: PubMed 7165009Oken 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.
- BackgroundTzekova, 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.
- Results for study 113708 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK1120212 in people with Cancer, run by GlaxoSmithKline at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total excretion of radioactivity (time frame: 11 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01387204, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2017.