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

Phase 2
18 Years
Open (Enrolling)
Neoplasms, Oral, Mouth Neoplasms

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Trial Information

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

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.

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

- 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.

5.-Patient must have an ECOG performance status ≤ 2 (see Appendix 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 ≥75,000/mcl

- PT/INR and PTT ≤1.5 x IULN


- Albumin ≥2.5 g/dL

- Total bilirubin ≤1.5 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

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 or current evidence/risk of retinal vein occlusion
(RVO) or central serous retinopathy (CSR), including a history of predisposing
factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension,
uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of
hyperviscosity or hypercoagulability syndromes) or visible retinal pathology as
assessed by ophthalmic exam that is considered a risk factor for RVO or CSR (such as
evidence of new optic disc cupping, evidence of new visual field defects, or
intraocular pressure > 21 mmHg).

- 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

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

14 days

Safety Issue:


Principal Investigator

Ravindra Uppaluri, M.D. Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Washington University School of Medicine


United States: Institutional Review Board

Study ID:




Start Date:

February 2013

Completion Date:

October 2014

Related Keywords:

  • Neoplasms, Oral
  • Mouth Neoplasms
  • Neoplasms
  • Carcinoma, Squamous Cell
  • Neoplasms, Squamous Cell
  • Mouth Neoplasms



Washington University School of MedicineSaint Louis, Missouri  63110