Leukaemia, Myelocytic, AcutePhase 1NCT01428427
Combination Study of GSK1120212 With Gemcitabine in Subjects With Solid Tumors
A Phase 1 study testing GSK1120212 and Gemcitabine in people with Leukaemia, Myelocytic, Acute, run by GlaxoSmithKline at 2 sites in United States.
Trial summary
MEK112111 is a dose-escalation, Phase IB, open-label, single-arm, multi-center study. The primary objective of the study is to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 dosed in combination with gemcitabine in subjects with solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukaemia, Myelocytic, Acute
- What is being tested?
- GSK1120212 and Gemcitabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- 12 Aug 2009to 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
- 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.
- Histologically or cytologically confirmed diagnosis of a solid tumor malignancy that is either relapsed or refractory, or potentially responsive to gemcitabine.
- Tumor Type criteria as listed in protocol.
- Male subjects must agree to use one of the contraception methods listed in protocol.
- A female subject is eligible to participate if she is of non-childbearing potential as defined in the protocol or postmenopausal as defined in the protocol. If of child-bearing potential, she agrees to use protocol specified contraceptive methods
- Adequate organ system function as defined below in the protocol.
Who cannot join
- Chemotherapy, radiotherapy, or immunotherapy within 28 days (or 42 days for prior nitrosoureas or mitomycin C) prior to the first dose of GSK1120212.
- Use of an investigational anti-cancer drug within 28 days or five 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.
- 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, dimethy sulfoxide (DMSO), or excipients (See protocol)
- Use of a prohibited medication (as defined in protocol) or current use of anticoagulants (e.g. warfarin, heparin, low molecular weight heparin) at therapeutic levels. Low dose (prophylactic) anticoagulants are permitted provided that subject's prothrombin time (PT) and partial thromboplastin time (PTT) meet entry criteria.
- Gastrointestinal disease predicted to interfere with absorption of an oral drug.
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- History of retinal vein occlusion (RVO) or central serous retinopathy.
- Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for retinal vein thrombosis.
- Glaucoma diagnosed within one month prior to study day 1.
- Intraocular pressure > 21mm Hg as measured by tonography.
- 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 months 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 v4.0) grade 1 from previous anti-cancer therapy.
- History of acute coronary within the past 24 weeks.
- QTc interval greater than or equal to 480 mili seconds (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 of hepatitis B or C. NOTE: Subjects with evidence of cleared hepatitis B infection are permitted [Hepatitis B Surface Antigen (HBsAg) negative, anti-HBsAg positive and anti Hepatitis B core antigen (HBc) positive.]
Trial locations and contacts
2 sites in 1 country.
United States2 sites
GSK Investigational Site
Nashville, Tennessee, 37203
GSK Investigational Site
San Antonio, Texas, 78229
About this study
Official title: A Phase IB Combination Study of MEK Inhibitor GSK1120212 With Gemcitabine in Subjects With Solid Tumors
MEK112111 is a dose-escalation, Phase IB, open-label, single-arm, multi-center study. The primary objective of the study is to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 dosed in combination with gemcitabine in subjects with solid tumors.
Read the detailed description
Subjects will be enrolled using a dose-escalation procedure in which the initial cohort receives a fraction of the GSK1120212 dose that achieved a dose limiting toxicity in a previous study and the recommended dose of gemcitabine. Escalation will proceed until the maximum tolerated doses are identified. These doses will be selected based on emerging safety data. Confirmation of the tolerability of the Recommended Phase II Dose (RP2D) will be explored in approximately 12 subjects. Subjects will continue on treatment until treatment discontinuation criteria are met (disease progression, intercurrent illness, adverse event or consent withdrawal).
- Conditions
- Leukaemia, Myelocytic, Acute
- Being tested
- GSK1120212, Gemcitabine
- Keywords
- Gemcitabine, MEK inhibitor, GSK1120212
- Medical subject headings
- Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1120212Drug
Continuous daily oral dosing while on study or disease progression (cycle = 28 days).
GemcitabineDrug
Dosing once weekly for 3 weeks in a 28 day cycle until disease progression.
| Study group | Role | What they receive |
|---|---|---|
| Cohort | Experimental | Dose escalation to maximum tolerated dose of GSK1120212 and Gemcitabine. Receives: Drug: GSK1120212; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events (AEs) and changes in laboratory values and vital signs.
Measured: From date of randomization until withdrawal from the study due to disease progression, AE, withdrawal of consent or study closure approximately 6 months after last subject was randomized.
Secondary outcomes (2)
Tumor response as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v 1.1
Measured: At screening and every 8 weeks until withdrawal from the study due to disease progression, AE, withdrawal of consent or study closure approximately 6 months after last subject was randomized.
drug levels in blood
Measured: first 15 days on study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2011 (estimated)
- Study start12 Aug 2009
- 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 (1)Papers the sponsor has linked to this study.
- Other trials for Leukaemia, Myelocytic, AcuteStudies 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
- 31 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
- NCT01428427
- Sponsor's protocol ID
- 112111
- Status last verified
- Nov 2017
- First submitted
- 10 Dec 2009
- Last updated
- 13 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Infante JR, Papadopoulos KP, Bendell JC, Patnaik A, Burris HA 3rd, Rasco D, Jones SF, Smith L, Cox DS, Durante M, Bellew KM, Park JJ, Le NT, Tolcher AW. A phase 1b study of trametinib, an oral Mitogen-activated protein kinase kinase (MEK) inhibitor, in combination with gemcitabine in advanced solid tumours. Eur J Cancer. 2013 Jun;49(9):2077-85. doi: 10.1016/j.ejca.2013.03.020. Epub 2013 Apr 11.
PubMed 23583440
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
- A Phase IB Combination Study of MEK Inhibitor GSK1120212 With Gemcitabine in Subjects With Solid Tumors
- ClinicalTrials.gov ID
- NCT01428427
- Acronym / sponsor ID
- 112111
- Conditions
- Leukaemia, Myelocytic, Acute
- Keywords
- Gemcitabine, MEK inhibitor, GSK1120212
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 12 Aug 2009 (actual)
- Primary completion
- 18 Jul 2011 (actual)
- Study completion
- 18 Jul 2011 (actual)
- First posted
- 5 Sep 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.
MEK112111 is a dose-escalation, Phase IB, open-label, single-arm, multi-center study. The primary objective of the study is to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 dosed in combination with gemcitabine in subjects with solid tumors.
Detailed description
Subjects will be enrolled using a dose-escalation procedure in which the initial cohort receives a fraction of the GSK1120212 dose that achieved a dose limiting toxicity in a previous study and the recommended dose of gemcitabine. Escalation will proceed until the maximum tolerated doses are identified. These doses will be selected based on emerging safety data. Confirmation of the tolerability of the Recommended Phase II Dose (RP2D) will be explored in approximately 12 subjects. Subjects will continue on treatment until treatment discontinuation criteria are met (disease progression, intercurrent illness, adverse event or consent withdrawal).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cohort | Experimental | Drug: GSK1120212, Drug: GemcitabineDose escalation to maximum tolerated dose of GSK1120212 and Gemcitabine. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
- Histologically or cytologically confirmed diagnosis of a solid tumor malignancy that is either relapsed or refractory, or potentially responsive to gemcitabine.
- Tumor Type criteria as listed in protocol.
Key exclusion criteria (17 listed)
- Chemotherapy, radiotherapy, or immunotherapy within 28 days (or 42 days for prior nitrosoureas or mitomycin C) prior to the first dose of GSK1120212.
- Use of an investigational anti-cancer drug within 28 days or five 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.
- 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, dimethy sulfoxide (DMSO), or excipients (See protocol)
- Use of a prohibited medication (as defined in protocol) or current use of anticoagulants (e.g. warfarin, heparin, low molecular weight heparin) at therapeutic levels. Low dose (prophylactic) anticoagulants are permitted provided that subject's prothrombin time (PT) and partial thromboplastin time (PTT) meet entry criteria.
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 |
|---|---|---|
| GSK1120212Continuous daily oral dosing while on study or disease progression (cycle = 28 days). | Drug | Cohort |
| GemcitabineDosing once weekly for 3 weeks in a 28 day cycle until disease progression. | Drug | Cohort |
Primary outcome
Adverse events (AEs) and changes in laboratory values and vital signs.
Time frame: From date of randomization until withdrawal from the study due to disease progression, AE, withdrawal of consent or study closure approximately 6 months after last subject was randomized.
2 secondary outcomes
Tumor response as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v 1.1
Time frame: At screening and every 8 weeks until withdrawal from the study due to disease progression, AE, withdrawal of consent or study closure approximately 6 months after last subject was randomized.
drug levels in blood
Time frame: first 15 days on study
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 23583440Infante JR, Papadopoulos KP, Bendell JC, Patnaik A, Burris HA 3rd, Rasco D, Jones SF, Smith L, Cox DS, Durante M, Bellew KM, Park JJ, Le NT, Tolcher AW. A phase 1b study of trametinib, an oral Mitogen-activated protein kinase kinase (MEK) inhibitor, in combination with gemcitabine in advanced solid tumours. Eur J Cancer. 2013 Jun;49(9):2077-85. doi: 10.1016/j.ejca.2013.03.020. Epub 2013 Apr 11.
- Results for study 112111 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
2 sites 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 Gemcitabine in people with Leukaemia, Myelocytic, Acute, run by GlaxoSmithKline at 2 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 17 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 2 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?
Adverse events (AEs) and changes in laboratory values and vital signs. (time frame: From date of randomization until withdrawal from the study due to disease progression, AE, withdrawal of consent or study closure approximately 6 months after last subject was randomized.). 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 NCT01428427, 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.