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CancerPhase 1NCT01725100

A Study to Determine the Relative Bioavailability of the MEK Inhibitor, Trametinib, in Subjects With Solid Tumor Malignancies

A Phase 1 study testing GSK1120212B (Standard DMSO content) and GSK1120212B (Lower DMSO content) in people with Cancer, run by GlaxoSmithKline at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open-label, randomized, single-dose, 2-treatment, 2-period, 2-way crossover study with incomplete wash-out in subjects with solid tumors to determine the relative bioavailability of test formulation with lower dimethyl sulfoxide (DMSO) content as compared with standard reference formulation trametinib. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer
What is being tested?
GSK1120212B (Standard DMSO content) and GSK1120212B (Lower DMSO content)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
4 sitesUnited States
Study dates
5 Feb 2013to 30 Jan 2015
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

  • Has provided signed, written informed consent.
  • Male or female, age >=18 years of age at the time of signing the informed consent form.
  • Has histologically or cytologically confirmed diagnosis of a solid tumor malignancy that is not responsive to standard therapy (ies) or for which there is no approved therapy.
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
  • All prior treatment-related toxicities must be National Cancer Institute - Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.0 <=Grade 1 (except alopecia) at the time of enrollment.
  • Has adequate baseline organ function as defined: ANC >=1.2×10^9/liter (L), hemoglobin>=9 gram (g)/deciliter (dL), Platelets>=75×10^9/L, partial thromboplastin time (PTT), prothrombin time (PT) and International normalization ratio (INR) <=1.5 times upper limit of normal (ULN), albumin >=2.5 g/dL, total bilirubin <=1.5 times ULN alanine aminotransferase (ALT) <=2.5 times ULN, Creatinine or calculated creatinine clearance >=50 milliliter (mL)/minute (min) and left ventricular ejection fraction (LVEF)>=lower limit of normal (LLN) by echocardiogram (ECHO) or multigated acquisition scan (MUGA).
  • 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, during the study and for 4 months following the last dose of study treatment.

Who cannot join

  • Prior exposure to a mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor.
  • Anti-cancer therapy (e.g., chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or major surgery) within 21 days prior to randomization; chemotherapy regimens without delayed toxicity within 14 days prior to randomization.
  • Female Subjects: Lactating or actively breastfeeding.
  • Has participated in a clinical trial and received investigational drug within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (IP), whichever is longer, prior to randomization in this study.
  • 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.
  • History or presence of hepatic insufficiency (excluding metastatic hepatic carcinoma).
Show all 18Show fewer
  • History of interstitial lung disease or pneumonitis.
  • Known Human Immunodeficiency Virus, Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection
  • Subjects with laboratory evidence of cleared HBV and HCV infection will be permitted.
  • Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study treatment, or excipients, or to DMSO.
  • Currently using a prohibited medication or requires the use of any of the prohibited medications during the study. Use of anticoagulants such as warfarin is permitted provided INR must be monitored in accordance with local institutional practice.
  • Has a history of another malignancy. Subjects who have been disease-free for 3 years or subjects with a history of a completely resected non-melanoma skin cancer and/or subjects with indolent second malignancies are eligible.
  • Any serious and/or unstable pre-existing medical disorder (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.
  • Has a history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
  • Symptomatic or untreated leptomeningeal or brain metastases, or spinal cord compression.
  • Left ventricular ejection fraction (LVEF), as measured by ECHO or MUGA scan, below the institutional LLN, or if a LLN does not exist at an institution, <50%.
  • QT interval corrected for heart rate using the Bazett formula (QTcB) >=480 millisecond (msec).
  • History or current evidence of cardiovascular risk including any of the following: current clinically significant uncontrolled arrhythmias, acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization, current >= Class II congestive heart failure as defined by New York Heart Association (NYHA), treatment-refractory hypertension defined as a blood pressure of systolic blood pressure (SBP) >140 millimeters of mercury (mmHg) and/or diastolic blood pressure (DBP) >90 mmHg which cannot be controlled by anti-hypertensive therapy, has an intra-cardiac defibrillator or permanent pacemaker and known cardiac metastases.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • GSK Investigational Site

    Goodyear, Arizona, 85338

  • GSK Investigational Site

    Nashville, Tennessee, 37203

  • GSK Investigational Site

    Sarasota, Florida, 34232

  • GSK Investigational Site

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: An Open-label, Randomized, 2-treatment, 2-period, 2-way Crossover, Single-dose Study to Determine the Relative Bioavailability of the MEK Inhibitor, Trametinib, in Subjects With Solid Tumor Malignancies

This is an open-label, randomized, single-dose, 2-treatment, 2-period, 2-way crossover study with incomplete wash-out in subjects with solid tumors to determine the relative bioavailability of test formulation with lower dimethyl sulfoxide (DMSO) content as compared with standard reference formulation trametinib.

Approximately 18 subjects will be randomized to receive either a single dose of Treatment A (standard target DMSO content [theoretical 11.3%] formulation of GSK1120212B) or a single dose of Treatment B (lower DMSO Content [approximately 9.5%] formulation of GSK1120212B) followed by a 7 day incomplete wash-out period, then a single dose of the other treatment.

Read more

Administration of the dose under fasted conditions in Periods 1 and 2 will be only on Day 1 followed by 7 days of serial blood sampling for PK analysis of plasma trametinib. Safety assessments, including assessment of AEs, clinical laboratory (hematology and clinical chemistry) and vital signs, will be made throughout the study.

After a subject completes the study, he or she may be eligible to enter study MEK114375, an open-label rollover study of trametinib (no wash-out period or follow-up visit required) and continue receiving trametinib. For those subjects who wish to discontinue or complete the current study and choose not enter the rollover study, a follow-up visit should be performed within 21 days after receiving the last dose of study treatment.

Conditions
Cancer
Being tested
GSK1120212B (Standard DMSO content), GSK1120212B (Lower DMSO content)
Keywords
GSK1120212, DMSO content, pharmacokinetics, solid tumors, MEK inhibitor, dissolution, trametinib, relative bioavailability
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK1120212B (Standard DMSO content)Drug

    Each tablet contains GSK1120212B equivalent to 2 mg of GSK1120212 as drug substance. The coated tablets have a standard DMSO content of theoretical 11.3%.

  • GSK1120212B (Lower DMSO content)Drug

    Each tablet contains GSK1120212B equivalent to 2 mg of GSK1120212 as drug substance. The coated tablets have a lower DMSO content approximately 9.5%.

Study groups in NCT01725100
Study groupRoleWhat they receive
Treatment A: GSK1120212B (Standard DMSO content)ExperimentalSubjects will receive Treatment A in Period 1 or 2 as single oral dose on Day 1 of Period 1 or 2 in fasting condition with water.
Receives: Drug: GSK1120212B (Standard DMSO content)
Treatment B: GSK1120212B (Lower DMSO content)ExperimentalSubjects will receive Treatment B in Period 1 or 2 as single oral dose on Day 1 of Period 1 or 2 in fasting condition with water.
Receives: Drug: GSK1120212B (Lower DMSO content)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Corrected Cmax of GSK1120212B

    Pharmacokinetic data will include corrected maximum plasma concentration (Cmax) of GSK1120212B. Comparison of Cmax will enable to determine the relative bioavailability of the test formulation with lower DMSO content (Treatment B) and the standard reference formulation (Treatment A). Period 2 PK parameters will be corrected for residual concentrations from Period 1 (based on individual estimates of t1/2) to remove the carry-over effect.

    Measured: Period 1 and 2: Day 1 pre-dose within 15 minutes (mins) of planned study treatment administration (serves as the 168-hour [hr] sample for Period 1), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 10 hrs post-dose; Days 2 to 7: post dose at 24 hrs (Day 2), 48 hrs (

  2. Corrected AUC(0-t) and AUC(0-inf) of GSK1120212B

    Pharmacokinetic data will include corrected area under the time-concentration curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t)) and AUC from zero to infinity (AUC(0-inf)) of GSK1120212B. Period 2 PK parameters will be corrected for residual concentrations from Period 1 (based on individual estimates of t1/2) to remove the carry-over effect.

    Measured: Period 1 and 2: Day 1 pre-dose within 15 mins of planned study treatment administration (serves as the 168-hr sample for Period 1), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 10 hrs post-dose; Days 2 to 7: post dose at 24 hrs (Day 2), 48 hrs (Day 3), 72 hrs (

  3. Corrected tmax of GSK1120212B

    Pharmacokinetic data will include corrected time of occurrence of Cmax (tmax) of GSK1120212B. Period 2 PK parameters will be corrected for residual concentrations from Period 1 (based on individual estimates of t1/2) to remove the carry-over effect.

    Measured: Period 1 and 2: Day 1 pre-dose within 15 mins of planned study treatment administration (serves as the 168-hr sample for Period 1), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 10 hrs post-dose; Days 2 to 7: post dose at 24 hrs (Day 2), 48 hrs (Day 3), 72 hrs (

Secondary outcomes (7)

  1. Uncorrected Cmax of GSK1120212B

    Pharmacokinetic data will include uncorrected Cmax of GSK1120212B.

    Measured: For Period 1 and 2 on Day 1: pre-dose within 15 mins of planned study treatment administration (serves as the 168-hr sample for Period 1), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 10 hrs post-dose; Days 2 to 7: post dose at 24 hrs (Day 2), 48 hrs (Day 3), 72

  2. Uncorrected AUC(0-t), AUC(0-inf) and AUC(0-24) of GSK1120212B

    Pharmacokinetic data will include uncorrected AUC(0-t), AUC(0-inf) and AUC from zero to 24 hrs AUC(0-24) of GSK1120212B.

    Measured: For Period 1 and 2 on Day 1: pre-dose within 15 mins of planned study treatment administration (serves as the 168-hr sample for Period 1), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 10 hrs post-dose; Days 2 to 7: post dose at 24 hrs (Day 2), 48 hrs (Day 3), 72

  3. Pre-dose concentration (C0) of GSK1120212B

    Pharmacokinetic data will include uncorrected C0 of GSK1120212B in Period 2

    Measured: Period 2: Day 1 pre-dose within 15 minutes (mins) of planned study treatment administration (serves as the 168-hour [hr] sample for Period 1.

  4. Elimination half life (t½) of GSK1120212B

    Pharmacokinetic data will include t1/2 of GSK1120212B.

    Measured: Period 1 and 2: Day 1 pre-dose within 15 mins of planned study treatment administration (serves as the 168-hr sample for Period 1), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 10 hrs post-dose; Days 2 to 7: post dose at 24 hrs (Day 2), 48 hrs (Day 3), 72 hrs (

  5. Safety of GSK1120212B as assessed by changes in vital signs measurements

    Safety data will include measurements of vital signs (blood pressure, pulse rate and temperature) at Baseline and end of the study.

    Measured: Through Day 36.

  6. Safety of GSK1120212B as assessed by changes in clinical laboratory tests

    Safety data will include assessments of clinical laboratory tests (hematology, clinical chemistry, coagulation and at Baseline and end of the study.

    Measured: Through Day 36.

  7. Safety of GSK1120212B as assessed by number of subjects with adverse events (AE)s

    Safety data will include recording of number of subjects with AEs.

    Measured: Through Day 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Nov 2012 (estimated)
  2. Study start5 Feb 2013
  3. Primary completion30 Jan 2015
  4. Study completion30 Jan 2015

Resources

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
Other
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01725100
Sponsor's protocol ID
114656
Status last verified
Nov 2017
First submitted
8 Nov 2012
Last updated
13 Nov 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK1120212B (Standard DMSO content) and GSK1120212B (Lower DMSO content) in people with Cancer, run by GlaxoSmithKline at 4 sites 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 8 inclusion and 18 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 4 sites 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?

Corrected Cmax of GSK1120212B (time frame: Period 1 and 2: Day 1 pre-dose within 15 minutes (mins) of planned study treatment administration (serves as the 168-hour [hr] sample for Period 1), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 10 hrs post-dose; Days 2 to 7: post dose at 24 hrs (Day 2), 48 hrs (). The study lists 3 primary outcomes in all. 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 NCT01725100.

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.

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