GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer

NCT01553851 | Completed Phase 2 Results

• 1 other identifier: 201205124
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neoplasms, Oral; Mouth Neoplasms

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline and Day 15

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

  Pre-post measure of CD44 expression using IHC.

  Baseline and Day 15

Secondary Outcomes (7)

• 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.

  Baseline and Day 15

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

  Baseline and Day 15

• Flow Cytometric Analysis of the Peripheral Blood and Tumor.

  Baseline, Day 14, and Day 15

• 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).

  Baseline and Day 14

• Safety of GSK1120212

  1st 4-6 week follow-up visit

Study Arms (1)

GSK1120212

EXPERIMENTAL

GSK1120212 2 mg PO daily for a total of 14 days with the intent of the last pill being the day before surgery.

Drug: GSK1120212

Interventions

GSK1120212 DRUG

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.

Also known as: Trametinib, Mekinist

GSK1120212

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Comprehensive Cancer Network: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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.

  PMID: 22086849 BACKGROUND

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Mouth Neoplasms

Interventions

trametinib

Condition Hierarchy (Ancestors)

Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases

Limitations and Caveats

Small number of treated patients. Short duration of GSK1120212 administration. Biopsy limitations precluded analysis of all patients.

Results Point of Contact

• Title: Dr. Douglas Atkins
• Organization: Washington University School of Medicine

datkins@dom.wustl.edu

314-747-8475

Study Officials

• Douglas Adkins, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2012
• First Posted: March 14, 2012
• Study Start: February 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 26, 2016
• Results First Posted: December 26, 2016

Record last verified: 2016-10

Locations

US (1)