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CancerPhase 1CancerNCT00955773

A Study of the GSK MEK Inhibitor GSK1120212 and Everolimus in Cancer Subjects

A Phase 1 study testing GSK1120212 plus everolimus in people with Cancer, run by GlaxoSmithKline at 3 sites in 2 countries.

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

The purpose of this study is to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 dosed in combination with everolimus in subjects with solid tumors. The escalation part of the study will determine the MTD. 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 plus everolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
64 participants
Where
3 sitesin 2 countries
Study dates
17 Aug 2009to 8 Nov 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

  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Age 18 years old or older and able to swallow oral medication.
  • Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology (ECOG) scale for Dose Escalation Cohort. Subjects with ECOG of 2 can be enrolled for expansion cohort.
  • Tumor Type criteria as listed in the protocol
  • Fasting glucose < 126mg/dL
  • Male subjects must agree to use one of the contraception methods listed in the protocol.
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  • A female subject is eligible to participate if she is of non-childbearing potential, and if she is of childbearing potential she must use protocol defined contraception methods.
  • Calcium phosphate product less than or equal to 4.0 mmol2/L2 (50 mg2/dL2)
  • Adequate organ system function as defined below in the protocol.

Who cannot join

  • Malignancies related to HIV or solid organ transplant.
  • Primary malignant brain tumors.
  • Chemotherapy, radiotherapy, or immunotherapy within 28 days (or 42 days for prior nitrosoureas or mitomycin C) prior to the first dose of GSK1120212. Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity are permitted with approval of a GSK Medical Monitor if dosing of that agent is terminated at least 14 days prior to the first dose of GSK1120212.
  • Use of an investigational anti-cancer drug within 28 days or 5 half-lives, whichever is shorter preceding the first dose of GSK1120212 - as long as a minimum of 14 days has passed between the last dose of the prior investigational anti-cancer drug and the first dose of GSK1120212.
  • Previous treatment with an mTOR inhibitor unless approved by GSK Medical Monitor.
  • Previous treatment with GSK1120212.
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  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug, DMSO, or excipients. (To date there are no known FDA approved drugs chemically related to GSK1120212).
  • Use of a prohibited medication (as defined in the protocol).
  • Current use of anticoagulants (e.g. warfarin, heparin) at therapeutic levels within seven days prior to the first dose of GSK1120212. Low dose (prophylactic) low molecular weight heparin (LMWH) is permitted provided that subject's PT and PTT meet entry criteria. Subjects required therapeutic levels of LMWH must receive approval from GSK Medical Monitor and monitored appropriately as clinically indicated.
  • Gastrointestinal disease predicted to interfere with absorption of an oral drug, systemic disease, major surgery, or social/psychological issues that in the opinion of investigators would jeopardize compliance with protocol.
  • History of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
  • Predisposing factors to RVO including uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, and coagulopathy.
  • Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for RVO or CSR.
  • Intraocular pressure > 21mm Hg as measured by tonography.
  • Glaucoma diagnosed within 1 month prior to study Day 1.
  • Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. Subjects previously treated for these conditions that are asymptomatic and off corticosteroids for at least two weeks are permitted. Subjects are not permitted to receive enzyme inducing anti-epileptic drugs (EIAEDs).
  • Unresolved toxicity greater than common terminology criteria for adverse events (CTCAE) grade 1 from previous anti-cancer therapy except alopecia (if applicable) unless agreed to by a GSK Medical Monitor and the Investigator.
  • History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks.
  • QTc interval ≥ 480 msecs.
  • Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
  • Pregnant or lactating female.
  • History or active hepatitis B or C.
  • History of HIV infection.
  • Subjects on chronic antifungal therapy.
  • Unwillingness or inability to follow the procedures outlined in the protocol.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

United States2 sites

  • GSK Investigational Site

    Nashville, Tennessee, 37203

  • GSK Investigational Site

    San Antonio, Texas, 78229

Other trials in United States

France1 site

  • GSK Investigational Site

    Paris, 75970

Other trials in France

About this study

Official title: An Open-Label, Dose-Escalation, Phase IB II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the MEK Inhibitor GSK1120212 in Combination With Oral Everolimus in Subjects With Solid Tumors

The purpose of this study is to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 dosed in combination with everolimus in subjects with solid tumors. The escalation part of the study will determine the MTD. The combination will be further explored in the expansion part in subjects with metastatic pancreatic cancer. In addition, subjects with KRAS mutant non-small cell lung cancer will be enrolled.

Read the detailed description

MEK112110 is a dose-escalation, open-label study to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 dosed in combination with everolimus in subjects with solid tumors. This will be accomplished using a dose-escalation procedure starting at low doses of GSK1120212 and everolimus. Dose escalation will continue based on predefined parameters until the maximum tolerated dose is identified. The recommended doses and regimens will be selected based on the safety and pharmacokinetic profiles. The clinical activity of GSK1120212 dosed in combination with everolimus will be explored further in an expansion cohort consisting of 20 subjects with metastatic pancreatic cancer. In addition a substudy will be conducted in 40 subjects with KRAS-mutant non-small cell lung cancer.

Conditions
Cancer
Being tested
GSK1120212 plus everolimus
Keywords
GSK1120212, everolimus, solid tumors, pancreatic cancer, non-small lung cancer, KRAS-mutant, cancer
Medical subject headings
Neoplasms, Pancreatic Neoplasms

What participants receive

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

  • GSK1120212 plus everolimusDrug

    Dose escalation will begin at low doses of GSK1120212 and everolimus, then gradually increase in future cohorts. Dose escalation will continue until a recommended combination dose is identified. The recommended combination dose will be used to treat pancreatic and lung cancer patients in later groups in this study.

Study groups in NCT00955773
Study groupRoleWhat they receive
Group IExperimental20 to 30 solid tumor subjects will be dosed with GSK1120212 in combination with everolimus to identify Maximum Tolerated Dose. Subjects will continue on study drug until disease progression or withdraw consent.
Receives: Drug: GSK1120212 plus everolimus
Group IIExperimental20 subjects with pancreatic cancer will receive the recommended dose identified in group I. Subjects will remain on study drug until disease progression or withdrawal from consent.
Receives: Drug: GSK1120212 plus everolimus
Group IIIExperimentalApproximately 40 lung cancer subjects will receive the recommended dose identified in group I. Subjects will remain on study until disease progression or withdrawal of consent.
Receives: Drug: GSK1120212 plus everolimus

What is being measured

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

  1. AEs and changes in laboratory values and vital signs

    Measured: 6 months

  2. Response rate, CR + PR of GSK1120212 and everolimus in KRAS-mutant NSCLC.

    Measured: 6 months

Secondary outcomes (6)

  1. GSK1120212 and everolimus PK parameters following repeat-dose (Day 15) administration of GSK1120212 and everolimus, including AUC(0-tau), Ct, Cmax, tmax, and t1/2, data permitting

    Measured: 6 months

  2. Tumor response as defined by RECIST 1.1.

    Measured: 6 months

  3. CA 19-9 levels compared to radiological response, per RECIST 1.1, over time for each pancreatic cancer subject

    Measured: 6 months

  4. Population PK parameters, oral clearance and oral volume of distribution of GSK1120212 and everolimus will be determined. Dependant upon the final compartmental model describing GSK1120212 + everolimus, add. PK may also be estimated.

    Measured: 6 months

  5. Clinical benefit response rate CR+PR+SD greater than 4mos

    Measured: 6 months

  6. Duration of response

    Measured: 6 months

Timeline

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

  1. First posted10 Aug 2009 (estimated)
  2. Study start17 Aug 2009
  3. Primary completion8 Nov 2011
  4. Study completion8 Nov 2011

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
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00955773
Sponsor's protocol ID
112110
Acronym
Cancer
Status last verified
Nov 2017
First submitted
6 Aug 2009
Last updated
9 Nov 2017
Results posted
No
Data monitoring committee
No

Publications

  • Tolcher AW, Bendell JC, Papadopoulos KP, Burris HA 3rd, Patnaik A, Jones SF, Rasco D, Cox DS, Durante M, Bellew KM, Park J, Le NT, Infante JR. A phase IB trial of the oral MEK inhibitor trametinib (GSK1120212) in combination with everolimus in patients with advanced solid tumors. Ann Oncol. 2015 Jan;26(1):58-64. doi: 10.1093/annonc/mdu482. Epub 2014 Oct 24.

    PubMed 25344362

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK1120212 plus everolimus in people with Cancer, run by GlaxoSmithKline at 3 sites in 2 countries.

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 26 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 9 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 3 sites in United States, France. 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?

AEs and changes in laboratory values and vital signs (time frame: 6 months). The study lists 2 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 NCT00955773, 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 9 Nov 2017.

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