CancerPhase 1NCT01416337
Absolute Bioavialability of GSK1120212
A Phase 1 study testing GSK1120212 and GSK1120212B in people with Cancer, run by GlaxoSmithKline at 1 site in United States.
Trial summary
A Phase I, single-center, open-label, single-persiod, combined single dose oral and IV microtracer study in subjects with solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- GSK1120212 and GSK1120212B
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jun 2011to 17 Dec 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female at least 18 years of age at the time of signing the informed consent form
- Histologically or cytologically confirmed diagnosis of a solid tumor that is not responsive to standard therapies or for which there is no approved therapy.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
- Body weight greater than or equal to 45 kg and a body mass index greater than or equal to 19 kg/m2 and less than 35 kg/m2 (inclusive)
- Able to swallow and retain oral medication
- Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
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- Women of child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control (see Section 7.1). Additionally, women of childbearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of study treatment;
- 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 from the time of first dose of study treatment until 16 weeks following the last dose of study treatment (based on the lifecycle of sperm).
- Must have adequate organ function as defined in Table 4:
- Table 4 Definitions for Adequate Baseline Organ Function System Laboratory Values Hematologic Absolute neutrophil count greater than or equal to 1.2 × 109/L Hemoglobin greater than or equal to 9 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 Total bilirubin less than or equal to 1.5 times ULN ALT less than or equal to 2.5 times ULN Creatinine or less than or equal to 1.5 times ULN Calculated creatinine clearance b or greater than or equal to 50 mL/min 24-hour urine creatinine clearance greater than or equal to 50 mL/min LVEF greater than or equal to LLNc by ECHO or MUGA
- INR greater1.5 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.
- Calculated by the Cockcroft-Gault formula (see Appendix 4).
- If LLN is not defined for a given institution, then ejection fraction must be greater than or equal to 50%. NOTE: Subjects with ALT or bilirubin values outside the range(s) in the table due to Gilbert's syndrome or asymptomatic gallstones are not excluded. Laboratory results obtained during Screening should be used to determine eligibility criteria. In situations where laboratory results are outside the permitted range, the investigator may opt to retest the subject and the subsequent within-range screening result may be used to confirm eligibility.
Who cannot join
- Currently receiving cancer therapy (e.g., chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or major surgery) 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 dosing of GSK1120212; use of any other investigational product within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (IP) (whichever is longest);
- Has participated in a 14C human research study in the 12 months prior to administration of study treatment;
- Current use of a prohibited medication (Section 8.2) or requires any of these medications during the study NOTE: Use of anticoagulants such as warfarin is permitted; however, INR must be monitored in accordance with local institutional practice.
- Has unresolved Grade 2 or greater toxicity (based on NCI-CTCAE, version 4.0) [NCI, 2009] from previous anti-cancer therapy except alopecia and Grade 2 anemia level.
- Has pre-existing Grade 2 or greater peripheral neuropathy.
- 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.
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- 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.
- 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.
- Has a history of interstitial lung disease or pneumonitis.
- 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 >21 mmHg as measured by tonography
- 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 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.
- QTcF (preferred) or QTcB greater than or equal to 480 msec.
- 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 >30 days prior to enrollment are eligible.
- History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to enrollment.
- History or evidence of current ≥ Class II congestive heart failure as defined by New York Heart Association [NYHA, 1994] (Appendix 3) NOTE: Subjects with BBB are not excluded from this study; however, if the underlying cause of the BBB is exclusionary or if the BBB is new onset (therefore, potentially reflective of an evolving cardiac condition), the subject should be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Determination of the Absolute Bioavailability of GSK1120212 Following a Single Oral Dose Co-Administered With an Intravenous Radiolabelled Microdose of GSK1120212 in Subjects With Solid Tumors
A Phase I, single-center, open-label, single-persiod, combined single dose oral and IV microtracer study in subjects with solid tumors.
Read the detailed description
This Phase I, open-label, non-randomized study is designed to determine the absolute bioavailability of the standard 2 mg tablet formulation of GSK1120212 co-administered with an intravenous microdose (5 μg) dose of [14C]-labelled GSK1120212 (7.4 kBq) in subjects with solid tumors. Pharmacokinetic sampleswill be obtained up to 10 days post-dose. Safety assessments, including assessment of adverse events, clinical laboratory values (hematology and clinical chemistry) and vital signs, will be performed throughout the study. After completing all assessments, eligible subjects may transition to MEK114375, an open-label, rollover study to continue treatment with GSK1120212.
- Conditions
- Cancer
- Being tested
- GSK1120212, GSK1120212B
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1120212Drug
2 mg single dose tablet on Day 1 of study
GSK1120212BDrug
A single administration of a slow 1 minute IV push on Day 1.
| Study group | Role | What they receive |
|---|---|---|
| Treatments A & B | Experimental | Single 2 mg GSK1120212 oral tablet, fasted Single IV dose of 5 ug (no more than 7.4 kBq or 200 nCi) [14C]GSK1120212 Both doses are given together. Receives: Drug: GSK1120212; Drug: GSK1120212B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the the absolute bioavailability of GSK1120212 following single oral tablet dose co-administered with an IV microdose.
Absolute bioavailability (F) of GSK1120212 calculated as the ratio of dose-normalized area under the concentration-time curve from time 0 (pre-dose) extrapolated to infinity (AUC(0-inf)) of oral to IV dosing
Measured: Pre-dose, 0.5h, 1h, 1.5h, 1.55h, 1.75h,2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 24h, 48h, 72h, 120h, 168h, and 240h.
Secondary outcomes (8)
Determine the single dose PK of GSK1120212 following oral administration.
Oral dosing: Cmax, tmax, AUC(0 24), area under the concentration-time curve from time 0 (pre-dose) to time t (AUC(0-t)), AUC(0-inf), t1/2, oral clearance (CL/F) of GSK1120212
Measured: Pre-dose, 0.5h, 1h, 1.5h, 1.75h,2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 24h, 48h, 72h, 120h, 168h, and 240h.
Determine the single dose PK of GSK1120212 following IV administration.
IV dosing: Cmax, tmax, AUC(0-24), AUC(0-t), AUC(0-inf), t1/2, systemic clearance (CL), and volume of distribution (Vd) of [14C]GSK1120212 and total drug-related material (radioactivity)
Measured: 1.55h, 1.75h,2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 24h, 48h, 72h, 120h, 168h, and 240h.
AEs
Number of AEs
Measured: Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 11, and follow-up.
Blood pressure
Change from baseline
Measured: Screening, Day 1, Day 2, and follow-up.
Pulse rate
Change from baseline
Measured: Screening, Day 1, Day 2, and follow-up.
ECG
Change from baseline
Measured: Screening, Day 1, Day 2, and follow-up.
Echo
Change from baseline
Measured: Screening day and follow-up
Clinical Laboratory data
Change from baseline
Measured: Screening, Day 1, and follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2011 (estimated)
- Study start20 Jun 2011
- Primary completion17 Dec 2011
- Study completion17 Dec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- Not applicable
- 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
- NCT01416337
- Sponsor's protocol ID
- 115064
- Status last verified
- Nov 2017
- First submitted
- 11 Aug 2011
- Last updated
- 13 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Leonowens C, Pendry C, Bauman J, Young GC, Ho M, Henriquez F, Fang L, Morrison RA, Orford K, Ouellet D. Concomitant oral and intravenous pharmacokinetics of trametinib, a MEK inhibitor, in subjects with solid tumours. Br J Clin Pharmacol. 2014 Sep;78(3):524-32. doi: 10.1111/bcp.12373.
PubMed 24606567
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
- Determination of the Absolute Bioavailability of GSK1120212 Following a Single Oral Dose Co-Administered With an Intravenous Radiolabelled Microdose of GSK1120212 in Subjects With Solid Tumors
- ClinicalTrials.gov ID
- NCT01416337
- Acronym / sponsor ID
- 115064
- Conditions
- Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 20 Jun 2011 (actual)
- Primary completion
- 17 Dec 2011 (actual)
- Study completion
- 17 Dec 2011 (actual)
- First posted
- 15 Aug 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.
A Phase I, single-center, open-label, single-persiod, combined single dose oral and IV microtracer study in subjects with solid tumors.
Detailed description
This Phase I, open-label, non-randomized study is designed to determine the absolute bioavailability of the standard 2 mg tablet formulation of GSK1120212 co-administered with an intravenous microdose (5 μg) dose of [14C]-labelled GSK1120212 (7.4 kBq) in subjects with solid tumors. Pharmacokinetic sampleswill be obtained up to 10 days post-dose. Safety assessments, including assessment of adverse events, clinical laboratory values (hematology and clinical chemistry) and vital signs, will be performed throughout the study. After completing all assessments, eligible subjects may transition to MEK114375, an open-label, rollover study to continue treatment with GSK1120212.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatments A & B | Experimental | Drug: GSK1120212, Drug: GSK1120212BSingle 2 mg GSK1120212 oral tablet, fasted Single IV dose of 5 ug (no more than 7.4 kBq or 200 nCi) [14C]GSK1120212 Both doses are given together. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male or female at least 18 years of age at the time of signing the informed consent form
- Histologically or cytologically confirmed diagnosis of a solid tumor that is not responsive to standard therapies or for which there is no approved therapy.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
- Body weight greater than or equal to 45 kg and a body mass index greater than or equal to 19 kg/m2 and less than 35 kg/m2 (inclusive)
- Able to swallow and retain oral medication
Key exclusion criteria (23 listed)
- Currently receiving cancer therapy (e.g., chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or major surgery) 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 dosing of GSK1120212; use of any other investigational product within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (IP) (whichever is longest);
- Has participated in a 14C human research study in the 12 months prior to administration of study treatment;
- Current use of a prohibited medication (Section 8.2) or requires any of these medications during the study NOTE: Use of anticoagulants such as warfarin is permitted; however, INR must be monitored in accordance with local institutional practice.
- Has unresolved Grade 2 or greater toxicity (based on NCI-CTCAE, version 4.0) [NCI, 2009] from previous anti-cancer therapy except alopecia and Grade 2 anemia level.
- Has pre-existing Grade 2 or greater peripheral neuropathy.
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 |
|---|---|---|
| GSK11202122 mg single dose tablet on Day 1 of study | Drug | Treatments A & B |
| GSK1120212BA single administration of a slow 1 minute IV push on Day 1. | Drug | Treatments A & B |
Primary outcome
Determine the the absolute bioavailability of GSK1120212 following single oral tablet dose co-administered with an IV microdose.
Time frame: Pre-dose, 0.5h, 1h, 1.5h, 1.55h, 1.75h,2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 24h, 48h, 72h, 120h, 168h, and 240h.
Absolute bioavailability (F) of GSK1120212 calculated as the ratio of dose-normalized area under the concentration-time curve from time 0 (pre-dose) extrapolated to infinity (AUC(0-inf)) of oral to IV dosing
8 secondary outcomes
Determine the single dose PK of GSK1120212 following oral administration.
Time frame: Pre-dose, 0.5h, 1h, 1.5h, 1.75h,2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 24h, 48h, 72h, 120h, 168h, and 240h.
Determine the single dose PK of GSK1120212 following IV administration.
Time frame: 1.55h, 1.75h,2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 24h, 48h, 72h, 120h, 168h, and 240h.
AEs
Time frame: Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 11, and follow-up.
Blood pressure
Time frame: Screening, Day 1, Day 2, and follow-up.
Pulse rate
Time frame: Screening, Day 1, Day 2, and follow-up.
ECG
Time frame: Screening, Day 1, Day 2, and follow-up.
Echo
Time frame: Screening day and follow-up
Clinical Laboratory data
Time frame: Screening, Day 1, and follow-up.
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.
- Derived from this study: PubMed 24606567Leonowens C, Pendry C, Bauman J, Young GC, Ho M, Henriquez F, Fang L, Morrison RA, Orford K, Ouellet D. Concomitant oral and intravenous pharmacokinetics of trametinib, a MEK inhibitor, in subjects with solid tumours. Br J Clin Pharmacol. 2014 Sep;78(3):524-32. doi: 10.1111/bcp.12373.
- Results for study 115064 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 and GSK1120212B 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 13 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?
Determine the the absolute bioavailability of GSK1120212 following single oral tablet dose co-administered with an IV microdose. (time frame: Pre-dose, 0.5h, 1h, 1.5h, 1.55h, 1.75h,2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 24h, 48h, 72h, 120h, 168h, and 240h.). 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 NCT01416337, which also lists 1 linked publication.
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; AzTrials last refreshed its copy on 3 Nov 2026.