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Trial record 53 of 7045 for:    Oral Cancer | ( Map: United States )

GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer

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ClinicalTrials.gov Identifier: NCT01553851
Recruitment Status : Completed
First Posted : March 14, 2012
Results First Posted : December 26, 2016
Last Update Posted : December 26, 2016
Sponsor:
Collaborator:
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Washington University School of Medicine

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Neoplasms, Oral
Mouth Neoplasms
Intervention Drug: GSK1120212
Enrollment 20
Recruitment Details  
Pre-assignment Details  
Arm/Group Title GSK1120212
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GSK1120212 2 mg PO daily for a total of 14 days with the intent of the last pill being the day before surgery.

GSK1120212: 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.

Period Title: Overall Study
Started 20
Completed 17
Not Completed 3
Reason Not Completed
Adverse Event             2
constipation             1
Arm/Group Title GSK1120212
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GSK1120212 2 mg PO daily for a total of 14 days with the intent of the last pill being the day before surgery.

GSK1120212: 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.

Overall Number of Baseline Participants 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Median (Full Range)
Unit of measure:  Years
Median Age (years) Number Analyzed 20 participants
59.5
(30 to 78)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Female
1
   5.0%
Male
19
  95.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   5.0%
White
18
  90.0%
More than one race
0
   0.0%
Unknown or Not Reported
1
   5.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 20 participants
20
Oral Cavity Sub-Site  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 20 participants
Tongue 7
Floor of Mouth 7
Retromolar trigone 5
Buccal 1
Clinical Stage   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 20 participants
Stage II 3
Stage III 3
Stage IV 14
[1]
Measure Description: Cancer staging uses the TNM system where T=primary tumor, N stands for nodes (indicating cancer has spread to lymph nodes, and M for metastasis. Numbering associated with staging or letters denotes an increase in number, size, location or severity. Stage II (T2N0) Stage III (T2N1, T3N1) Stage IV(T2N2a,T2N2b,T3N2b,T4aN0,T4aN1,T4aN2b,T4aN2c)
History of Smoking and/or Alcohol Abuse  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 20 participants
18
1.Primary Outcome
Title 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.
Hide Description Pre-post measure of p-EKP expression was measured by change in staining intensity and quartile distribution.
Time Frame Baseline and Day 15
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Hide Analysis Population Description
Only15 of the 17 participants had sufficient pre- and post-treatment biopsies with sufficient tumor content to be evaluated for this biomarker assessment.
Arm/Group Title GSK1120212
Hide Arm/Group Description:

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

GSK1120212: 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.

Overall Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: participants
Decrease in p-EPK1/2 expression 7
Inverse relationship in p-EPK expression 2
No change in p-EKP expression 3
Increase in p-EKP expression 3
2.Primary Outcome
Title Number of Participants With Changes in TumorCell Surface CD44 Expression After Treatment With GSK1120212.
Hide Description Pre-post measure of CD44 expression using IHC.
Time Frame Baseline and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title GSK1120212
Hide Arm/Group Description:

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

GSK1120212: 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.

Overall Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: Participants
3
3.Secondary Outcome
Title 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.
Hide Description [Not Specified]
Time Frame Baseline and Day 15
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Hide Analysis Population Description
There was an insufficient amount of tissue to collected. The data was not collected and the outcome measure was not analyzed.
Arm/Group Title GSK1120212
Hide Arm/Group Description:

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

GSK1120212: 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.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Percentage of Participants With Clinical Response Induced by GSK1120212, as Determined by Change in Tumor Size.
Hide Description 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.
Time Frame Baseline and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title GSK1120212
Hide Arm/Group Description:

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

GSK1120212: 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.

Overall Number of Participants Analyzed 17
Measure Type: Number
Unit of Measure: percentage of participants
76
5.Secondary Outcome
Title Flow Cytometric Analysis of the Peripheral Blood and Tumor.
Hide Description

Peripheral blood - baseline and Day 14

Tumor - baseline and Day 15

Time Frame Baseline, Day 14, and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
There was an insufficient amount of tissue to collected. The data was not collected and the outcome measure was not analyzed.
Arm/Group Title GSK1120212
Hide Arm/Group Description:

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

GSK1120212: 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.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title 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).
Hide Description [Not Specified]
Time Frame Baseline and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Seven patients did not meet protocol-defined tumor size criteria (n=3), withdrew from study (n=3) or declined post GSK1120212 FDG-PET/CT(n=1)
Arm/Group Title GSK1120212
Hide Arm/Group Description:

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

GSK1120212: 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.

Overall Number of Participants Analyzed 13
Median (Full Range)
Unit of Measure: percentage change in SUVmax
-25
(-52 to -6)
7.Secondary Outcome
Title Safety of GSK1120212
Hide Description Number of adverse events were monitored for 30 day following last dose of GSK1120212
Time Frame 1st 4-6 week follow-up visit
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title GSK1120212
Hide Arm/Group Description:

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

GSK1120212: 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.

Overall Number of Participants Analyzed 20
Measure Type: Number
Unit of Measure: Adverse events
Neutrophil decrease (Grade 1-2) 1
Thrombocytopenia(Grade 1-2) 1
Colitis( Grade 3-4) 1
Diarrhea (Grade 1-2) 3
Mucositis( Grade 3-4) 1
Nausea (Grade 1-2) 2
Doudenal Perforation (Grade 3-4) 1
Stomach Cramps(Grade 1-2) 1
Lung Infection (Grade 3-4) 1
Rash, acneiform (Grade 1-2) 9
Pruritis (Grade 1-2) 1
Fatigue(Grade 1-2) 2
Fever (Grade 1-2) 1
Alkaline Phosphatase (Grade 1-2) 3
AST (Grade 1-2) 4
ALT (Grade 1-2) 2
Blurry Vision (Grade 1-2) 1
Hypotension (Grade 1-2) 1
8.Secondary Outcome
Title Percent Change in Tumor Size Area
Hide Description [Not Specified]
Time Frame Baseline and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Quantitative changes in tumor size based on clinical examination of area of tumor at baseline and after GSK1120212 based on two dimensional measurements.
Arm/Group Title GSK1120212
Hide Arm/Group Description:

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

GSK1120212: 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.

Overall Number of Participants Analyzed 17
Median (Full Range)
Unit of Measure: percent change in tumor size area
-46
(-74 to -14)
9.Secondary Outcome
Title Percent of Participants With Metabolic Changes in OCSCC Using FDG-PET/CT Imaging.
Hide Description 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.
Time Frame Baseline and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Seven patients did not meet protocol-defined tumor size criteria (n=3), withdrew from study (n=3) or declined post GSK1120212 FDG-PET/CT(n=1)
Arm/Group Title GSK1120212
Hide Arm/Group Description:

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

GSK1120212: 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.

Overall Number of Participants Analyzed 13
Measure Type: Number
Unit of Measure: percentage of participants
85
Time Frame Adverse events were collected for 4-6 weeks.
Adverse Event Reporting Description AE grade 3 or higher will be followed for 3-6 months and considered at least possibly related
 
Arm/Group Title GSK1120212
Hide Arm/Group Description

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

GSK1120212: 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.

All-Cause Mortality
GSK1120212
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
GSK1120212
Affected / at Risk (%)
Total   6/20 (30.00%) 
Blood and lymphatic system disorders   
Anemia  1  2/20 (10.00%) 
Gastrointestinal disorders   
Colitis  1  2/20 (10.00%) 
Mucositis Oral  1  1/20 (5.00%) 
Vomitting  1  1/20 (5.00%) 
Duodenal Perforation  1  2/20 (10.00%) 
Infections and infestations   
Sepsis  1  1/20 (5.00%) 
Infections and infestations -Other: Skin Infection  1  1/20 (5.00%) 
Shingles  1  1/20 (5.00%) 
Lung Infection  1  1/20 (5.00%) 
Investigations   
Activated partial thromboplastin time prolonged  1  1/20 (5.00%) 
Alanine aminotransferase increased  1  1/20 (5.00%) 
Aspartate aminotransferase increased  1  1/20 (5.00%) 
Blood Bilirubin increased  1  1/20 (5.00%) 
Neutrophil count increased  1  1/20 (5.00%) 
Platelet count decreased  1  1/20 (5.00%) 
White cell count decreased  1  1/20 (5.00%) 
Lymphocyte count decreased  1  1/20 (5.00%) 
Metabolism and nutrition disorders   
Hyperglycemia  1  1/20 (5.00%) 
Hypoalbuminemia  1  3/20 (15.00%) 
Hypocalcemia  1  1/20 (5.00%) 
Hyponatremia  1  1/20 (5.00%) 
Hypophosphatemia  1  1/20 (5.00%) 
Musculoskeletal and connective tissue disorders   
Neck soft tissue necrosis  1  1/20 (5.00%) 
Vascular disorders   
Hypertension  1  1/20 (5.00%) 
Hypotension  1  1/20 (5.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
GSK1120212
Affected / at Risk (%)
Total   14/20 (70.00%) 
Blood and lymphatic system disorders   
Anemia  1  9/20 (45.00%) 
Cardiac disorders   
Hypertension  1  1/20 (5.00%) 
Eye disorders   
Blurred vision  1  1/20 (5.00%) 
Gastrointestinal disorders   
Abdominal pain  1  1/20 (5.00%) 
Constipation  1  3/20 (15.00%) 
Diarrhea  1  4/20 (20.00%) 
Dry Mouth  1  1/20 (5.00%) 
Mucositis Oral  1  1/20 (5.00%) 
Nausea  1  4/20 (20.00%) 
Oral Dysesthesia  1  1/20 (5.00%) 
Oral Hemorrhage  1  1/20 (5.00%) 
Oral pain  1  6/20 (30.00%) 
Small intestines obstruction  1  1/20 (5.00%) 
Stomach pain  1  1/20 (5.00%) 
Vomitting  1  1/20 (5.00%) 
General disorders   
Chills  1  2/20 (10.00%) 
Edema limbs  1  2/20 (10.00%) 
Fatigue  1  3/20 (15.00%) 
Fever  1  1/20 (5.00%) 
Localized Edema  1  1/20 (5.00%) 
Infections and infestations   
Papulopustular rash  1  2/20 (10.00%) 
Infections and infestation-Other: Skin infection  1  1/20 (5.00%) 
Injury, poisoning and procedural complications   
Tracheostomy site bleed  1  1/20 (5.00%) 
Investigations   
Alanine aminotransferase increased  1  3/20 (15.00%) 
Alkaline Phosphatase increased  1  3/20 (15.00%) 
Aspartate aminotransferase increased  1  5/20 (25.00%) 
Creatinine increased  1  2/20 (10.00%) 
INR increased  1  1/20 (5.00%) 
Platelet count decreased  1  5/20 (25.00%) 
Lymphocyte decreased  1  4/20 (20.00%) 
Metabolism and nutrition disorders   
Anorexia  1  2/20 (10.00%) 
Hyperglycemia  1  2/20 (10.00%) 
Hyperkalemia  1  7/20 (35.00%) 
Hypernatremia  1  2/20 (10.00%) 
Hypoalbuminemia  1  1/20 (5.00%) 
Hypocalcemia  1  6/20 (30.00%) 
Hypokalemia  1  3/20 (15.00%) 
Hypomagnesemia  1  1/20 (5.00%) 
Hyponatremia  1  6/20 (30.00%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  1/20 (5.00%) 
Pain in extremity  1  1/20 (5.00%) 
Nervous system disorders   
Dizziness  1  2/20 (10.00%) 
Dysarthria  1  1/20 (5.00%) 
Headache  1  2/20 (10.00%) 
Peripheral sensory neuropathy  1  1/20 (5.00%) 
Psychiatric disorders   
Anxiety  1  2/20 (10.00%) 
Confusion  1  1/20 (5.00%) 
Insomnia  1  3/20 (15.00%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/20 (10.00%) 
Dyspnea  1  1/20 (5.00%) 
Hoarseness  1  1/20 (5.00%) 
Sore throat  1  2/20 (10.00%) 
Skin and subcutaneous tissue disorders   
Dry skin  1  1/20 (5.00%) 
Pruritis  1  1/20 (5.00%) 
Rash acneiform  1  8/20 (40.00%) 
Rash maculo-papular  1  1/20 (5.00%) 
Hyperhidrosis  1  1/20 (5.00%) 
Vascular disorders   
Hot flashes  1  1/20 (5.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Small number of treated patients. Short duration of GSK1120212 administration. Biopsy limitations precluded analysis of all patients.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Douglas Atkins
Organization: Washington University School of Medicine
Phone: 314-747-8475
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01553851     History of Changes
Other Study ID Numbers: 201205124
First Submitted: March 12, 2012
First Posted: March 14, 2012
Results First Submitted: September 6, 2016
Results First Posted: December 26, 2016
Last Update Posted: December 26, 2016