GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer
Condition: Neoplasms, Oral; Mouth Neoplasms
MeSH terms: Neoplasms; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Mouth Neoplasms
Intervention: GSK1120212
Intervention description: 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.
Intervention MeSH terms: Trametinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility 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.

          -  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.

          -  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.

        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 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.

          -  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