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Neoplasms, OralPhase 2NCT01553851

GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer

A Phase 2 study testing GSK1120212 in people with Neoplasms, Oral and Mouth Neoplasms, run by Washington University School of Medicine at 1 site in United States.

Completed

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

Official record
Search all trials

Trial summary

This phase II trial studies how trametinib effects tumor cells in patients with oral cavity squamous cell carcinoma that can be removed by surgery. Trametinib may shrink the tumor by blocking an enzyme pathway needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms, Oral, Mouth Neoplasms
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
20 participants
Where
1 siteUnited States
Study dates
Feb 2013to Dec 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Patient must have histologically or cytologically confirmed oral cavity squamous cell carcinoma of stage 2, 3, 4a, or 4b.
  • Patients by definition have disease at the primary tumor site of at least 2 centimeters.
  • Patient's treatment plan must include primary tumor site biopsy followed by gross excision of the primary tumor site at a separate operative procedure.
  • Patients with concurrent primary head and neck tumors that will be resected as part of treatment plan are considered eligible
  • Patients with head and neck cancer recurrence requiring surgery with no history of prior chemotherapy or radiation therapy are considered eligible.
  • Patient must be ≥ 18 years of age.
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  • Patient must have an ECOG performance status ≤ 1
  • Patient must have normal bone marrow and organ function as defined below:
  • Absolute neutrophil count ≥1,200/mcl
  • Hemoglobin ≥9.0 g/dL
  • Platelets ≥100,000/mcl
  • PT/INR and PTT ≤1.3 x IULN (Subjects on Coumadin are included if their coagulation is within a normal therapeutic range)
  • LVEF ≥ILLN (by ECHO or MUGA)
  • Albumin ≥2.5 g/dL
  • Total bilirubin ≤1.5 x IULN
  • AST(SGOT)/ALT(SGPT) ≤2.5 x IULN
  • Creatinine ≤1.5 x IULN OR Creatinine clearance ≥50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, intrauterine device, male partner sterilization, or complete abstinence) prior to study entry, for the duration of study participation, and for at least 4 months after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Patient must have the ability to swallow and retain orally administered medication.
  • Patient (or legally authorized representative if applicable) must be able to understand and willing to sign an IRB approved written informed consent document.
  • Both men and women and members of all races and ethnic groups are eligible for this trial.

Who cannot join

  • Patients must not have had any prior head and neck cancer treatment.
  • Patient must not have a history of other malignancy ≤ 3 years previous with the exception of previous head and neck cancer treated only by surgery basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
  • Patients must not be receiving any other investigational agents.
  • Patient must not have a history of retinal vein occlusion (RVO).
  • Patient must not have known symptomatic leptomeningeal or brain metastases or spinal cord compression.
  • Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to GSK1120212 or other agents used in the study.
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  • Patient must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
  • Patient must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patient must not be pregnant and/or breastfeeding.
  • Patient must not be known to be HIV-positive, hepatitis B-positive, or hepatitis C-positive (with the exception of chronic or cleared HBV or HCV infection, which will be allowed).
  • Patient must not be taking any herbal supplements during the study (including but not limited to St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, or ginseng). If a potential patient is taking any herbal supplements, s/he must discontinue prior to beginning study treatment.
  • Patient must not have any history or evidence of cardiovascular risk including any of the following:
  • QTcB ≥ 480 msec
  • History or evidence of current clinically significant uncontrolled arrhythmias (exception: subjects with controlled atrial fibrillation for > 30 days prior to registration are eligible)
  • History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to registration
  • History or evidence of current ≥ Class II congestive heart failure as defined by New York Heart Association.
  • Abnormal cardiac valve morphology (≥ grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.
  • Treated refractory hypertension defined as a blood pressure of systolic >140 mmHg and/or diastolic >90 mmHg which cannot be controlled by antihypertensive therapy.
  • Intra-cardiac defibrillator or permanent pacemaker
  • Cardiac metastases
  • Patient must not have a history of interstitial lung disease or pneumonitis
  • Current use of a prohibited medication

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase II Window of Opportunity Trial With GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer

This phase II trial studies how trametinib effects tumor cells in patients with oral cavity squamous cell carcinoma that can be removed by surgery. Trametinib may shrink the tumor by blocking an enzyme pathway needed for cell growth.

Read the detailed description

The rationale for this study in oral cavity squamous cell carcinomas rests on pre-clinical findings demonstrating that (a) activation of the ERK1/2 kinases is associated with aggressive features, (b) this aggressive phenotype is directly linked to expression of CD44, a cell surface hyaluronan receptor and (c) this association between activated ERK1/2 and CD44 is also identified in human cell lines and primary tumors. These data suggest that ERK1/2 is targetable biochemical pathway in CD44 expressing cells. These cells represent putative cancer stem cells or tumor initiating cells that have been associated with worse patient outcomes. Thus, the application of GSK1120212 to target OCSCC is a specific translational application of our laboratory findings.

Being tested
GSK1120212
Medical subject headings
Mouth Neoplasms

What participants receive

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

  • GSK1120212Drug

    Also called Trametinib, Mekinist

    Trametinib (GSK1120212) is a selective MEK1 and MEK2 inhibitor with selective activity towards BRAF and RAS mutant cancer cell lines and hematopoietic cancer cells from AML and CML origins.

Study groups in NCT01553851
Study groupRoleWhat they receive
GSK1120212ExperimentalGSK1120212 2 mg PO daily for a total of 14 days with the intent of the last pill being the day before surgery.
Receives: Drug: GSK1120212

What is being measured

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

  1. Number of Participants With Changes in Putative Tumor Initiating Cell Populations as Defined by Cell Surface CD44 and Intracellular Phospho-ERK1/2 Staining After Treatment With GSK1120212.

    Pre-post measure of p-EKP expression was measured by change in staining intensity and quartile distribution.

    Measured: Baseline and Day 15

  2. Number of Participants With Changes in TumorCell Surface CD44 Expression After Treatment With GSK1120212.

    Pre-post measure of CD44 expression using IHC.

    Measured: Baseline and Day 15

Secondary outcomes (7)

  1. Tumor Specific Findings for Pathologic Changes Including Proliferation (Ki-67 Staining), Tumor Vasculature Staining (Microvessel Density), ERK1/2 Mediated Changes in p27 (Kip1) & Flow Cytometric Analysis of the Peripheral Blood & Tumor.

    Measured: Baseline and Day 15

  2. Percentage of Participants With Clinical Response Induced by GSK1120212, as Determined by Change in Tumor Size.

    Clinical Response was evaluted by quantitative changes in tumor size based on clinical examination of area of tumor at baseline and after GSK1120212 based on two dimensional measurements.

    Measured: Baseline and Day 15

  3. Flow Cytometric Analysis of the Peripheral Blood and Tumor.

    Peripheral blood - baseline and Day 14

    Tumor - baseline and Day 15

    Measured: Baseline, Day 14, and Day 15

  4. Percent Change in Maximum Standard Uptake Value in Oral Cavity Saqumous Cell Carcinoma (OCSCC) Using F18-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT).

    Measured: Baseline and Day 14

  5. Safety of GSK1120212

    Number of adverse events were monitored for 30 day following last dose of GSK1120212

    Measured: 1st 4-6 week follow-up visit

  6. Percent Change in Tumor Size Area

    Measured: Baseline and Day 15

  7. Percent of Participants With Metabolic Changes in OCSCC Using FDG-PET/CT Imaging.

    Intratumarol metabolic changes were evaluated by changes in in SUVmax in the primary tumor; quantitative analysis SUVmax with the primary tumor site was determined within a volume of interest around the tumor using a Siemens eSoft workstation.

    Measured: Baseline and Day 14

Timeline

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

  1. First posted14 Mar 2012 (estimated)
  2. Study startFeb 2013
  3. Primary completionJun 2015
  4. Study completionDec 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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01553851
Sponsor's protocol ID
201205124
Status last verified
Oct 2016
First submitted
12 Mar 2012
Last updated
26 Dec 2016
Data monitoring committee
No

Publications

  • Judd NP, Winkler AE, Murillo-Sauca O, Brotman JJ, Law JH, Lewis JS Jr, Dunn GP, Bui JD, Sunwoo JB, Uppaluri R. ERK1/2 regulation of CD44 modulates oral cancer aggressiveness. Cancer Res. 2012 Jan 1;72(1):365-74. doi: 10.1158/0008-5472.CAN-11-1831. Epub 2011 Nov 15.

    PubMed 22086849

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK1120212 in people with Neoplasms, Oral and Mouth Neoplasms, run by Washington University School of Medicine 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 21 inclusion and 22 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 26 Dec 2016. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Changes in Putative Tumor Initiating Cell Populations as Defined by Cell Surface CD44 and Intracellular Phospho-ERK1/2 Staining After Treatment With GSK1120212. (time frame: Baseline and Day 15). 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 NCT01553851, 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 26 Dec 2016.

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