Trial record 1 of 1 for:    NCT01553851
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GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Washington University School of Medicine
Sponsor:
Collaborator:
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01553851
First received: March 12, 2012
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Neoplasms, Oral
Mouth Neoplasms
Drug: GSK1120212
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Window of Opportunity Trial With GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • To analyze tumor specific 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor specific findings will be analyzed 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. [ Time Frame: Baseline and Day 15 ] [ Designated as safety issue: No ]
  • To measure the size of the tumors by clinical exam to define whether GSK1120212 induces a clinical response [ Time Frame: Baseline and Day 15 ] [ Designated as safety issue: No ]
  • Flow cytometric analysis of the peripheral blood and tumor. [ Time Frame: Baseline, Day 14, and Day 15 ] [ Designated as safety issue: No ]

    Peripheral blood - baseline and Day 14

    Tumor - baseline and Day 15


  • Determine whether GSK1120212 induces intratumoral metabolic changes in OCSCC using FDG-PET/CT imaging. [ Time Frame: Baseline and Day 14 ] [ Designated as safety issue: No ]
  • Safety of GSK1120212 [ Time Frame: 1st 4-6 week follow-up visit ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: February 2013
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK1120212
GSK1120212 2 mg PO daily for a total of 14 days prior to date of surgery.
Drug: GSK1120212

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • Patient must be ≥ 18 years of age.
  • Patient must have an ECOG performance status ≤ 2
  • Patient must have normal bone marrow and organ function as defined below:

    • Absolute neutrophil count ≥1,200/mcl
    • Hemoglobin ≥9.0 g/dL
    • Platelets ≥75,000/mcl
    • PT/INR and PTT ≤1.5 x IULN
    • LVEF ≥ILLN (by ECHO)
    • 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, abstinence) prior to study entry and for the duration of study participation. 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.

Exclusion Criteria:

  • 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 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.
  • 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.
    • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01553851

Contacts
Contact: Ravindra Uppaluri, M.D., Ph.D. 314-362-6599 uppalurir@ent.wustl.edu
Contact: Casey Rowe, MS 314-362-8547 rowec@wudosis.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Ravindra Uppaluri, M.D., Ph.D.    314-362-6599    uppalurir@ent.wustl.edu   
Contact: Casey Rowe, MS    314-362-8547    rowec@wudosis.wustl.edu   
Sub-Investigator: Douglas Adkins, M.D.         
Sub-Investigator: Rajendra Apte, M.D.         
Sub-Investigator: Farrokh Dehdashti, M.D.         
Sub-Investigator: Jason Diaz, M.D.         
Sub-Investigator: Bruce Haughley, MB. ChB         
Sub-Investigator: Dorina Kallogjeri, M.D., MPH         
Sub-Investigator: James Lewis, M.D.         
Principal Investigator: Loren Michel, M.D.         
Sub-Investigator: Bruce Nussenbaum, M.D.         
Sub-Investigator: Randal Paniello, M.D.         
Sub-Investigator: Jay Piccirillo, M.D.         
Sub-Investigator: Jason Rich, M.D.         
Sub-Investigator: Barry Siegel, M.D.         
Sub-Investigator: Tanya Wildes, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
National Comprehensive Cancer Network
Investigators
Principal Investigator: Ravindra Uppaluri, M.D. Ph.D. Washington University School of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01553851     History of Changes
Other Study ID Numbers: 201205124
Study First Received: March 12, 2012
Last Updated: March 24, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Carcinoma, Squamous Cell
Neoplasms, Squamous Cell
Mouth Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Head and Neck Neoplasms
Neoplasms by Site
Mouth Diseases
Stomatognathic Diseases
Trametinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014