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Defining the Triple Negative Breast Cancer Kinome Response to GSK1120212

18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Defining the Triple Negative Breast Cancer Kinome Response to GSK1120212

In this study the investigators want to look at the activity of kinases when a particular
experimental drug called GSK1120212 is administered. GSK1120212 blocks a kinase called MEK.
GSK1120212 is not yet approved by the FDA for use in breast cancer patients. The
investigators want to give subjects GSK1120212 for a short period of time (one week) to see
how MEK and the other kinases function in cancer cells both before and after the study drug
is given. The investigators are giving this drug for research purposes only. The length of
time it is being given is not intended to treat cancer.

Research into treatments for breast cancer relies more and more on an understanding of how
the cells of tumor tissue act when they are exposed to a new or different drug. To find
these new or different drugs to treat cancer, researchers are looking at proteins that help
cancer cells grow, such as a group of proteins called Kinases. This is important because
many of the newest cancer drugs are designed to block kinases causing the cancer cells to
die and the tumors to shrink. However, blocking only one of the kinases at a time is often
less effective than the investigators expected because when you block one kinase another can
take its place. For this reason, the investigators may need to treat breast cancer with
more than one kinase-blocking drug at a time. However, the investigators don't yet know what
the best combination of drugs should be, because it is hard to measure all the possible
kinases. Previous studies have only been able to identify less than 10% of the hundreds of
kinases in cancer cells.

Recently researchers here at UNC have developed a process that can identify may (more than
half) of these kinases. This can tell us which kinases need to be blocked at the same time
to make tumors shrink so that the investigators can design the best combinations of kinase
blocking drugs for triple negative breast cancer. This is especially important for
individuals with triple negative breast cancer (TNBC) because there are fewer drugs
available that can block molecules that affect tumor growth. The investigators believe that
kinase-blocking drugs have the potential to be a more effective treatment for people with

Inclusion Criteria:

- Histologically confirmed TNBC (i.e., ER negative, PR negative (each <10% staining by
immunohistochemistry) and Her2 negative (0-1+ or FISH non-amplified; by clinical
assay on primary tumor)

- Stage I-IIIc disease:

- Scheduled for lumpectomy or mastectomy

- No prior or current therapy for breast cancer

- Not considered candidate for therapeutic neoadjuvant treatment

- For stage IV disease:

- Scheduled for surgical resection of oligometastatic disease

- Previously untreated for breast cancer

- Subject enrolls into LCCC9819

- ECOG Performance Status 0-2

- Normal end organ function as defined by the following:

- Absolute neutrophil count (ANC)≥ 1.2 X 109/L;

- Hemoglobin ≥ 9 g/dL;

- Platelets ≥ 75 X 109/L;

- PT/INR and PTT ≤ 1.2 X upper limit of normal (ULN);

- Albumin ≥ 2.5 g/dL

- Total bilirubin ≤ 1.5 x ULN mg/dL

- AST and ALT ≤ 2.5 X ULN

- Creatinine ≤ 1.5 X ULN OR Calculated creatinine clearance ≥50 mL/min OR
24-hour urine creatinine clearance ≥50 mL/min;

- Ejection fraction ≥ LLN by ECHO (preferred) or MUGA

- Age ≥18 years

- Willing to use adequate contraception if applicable, and to continue use for 4 weeks
post last dose of GSK1120212

- Sufficient fresh or frozen tissue remaining from pre-treatment core incisional biopsy
or willing to undergo biopsy for research purposes only (approximately 10mg or one
core's worth of tissue needed)

- Surgeon and Medical Oncologist agree one week window trial appropriate/safe for trial
candidate and that surgery appointment can accommodate a 7 day (one week) treatment

- Able to swallow oral medications

Exclusion Criteria

- Pregnant or lactating female

- Currently active GI disease, or prior surgery that may affect ability to absorb oral

- Prior radiation therapy to the target lesion

- History or current evidence/risk of retinal vein occlusion (RVO) or central serous
retinopathy (CSR):

- History of RVO or CSR, or 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)

- Current use of a prohibited medication or requires any of these medications during
treatment with GSK1120212 (see section 4.6).

- Use of an investigational anti-cancer drug within 28 days or five half-lives,
whichever is shorter, prior to the first dose of GSK1120212. A minimum of 10 days
between termination of the investigational drug and administration of GSK1120212 is
required. In addition, any drug-related toxicity should have recovered to Grade 1 or

- Prior treatment with MEK or BRAF inhibitors

- Any major radiotherapy, or immunotherapy within the last four weeks; use of
erythropoietin replacement or bisphosphonates is considered supportive care and their
use is permitted

- Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated
respiratory, hepatic, renal, or cardiac disease)

- History or evidence of cardiovascular risk including any of the following:

- QTc interval >/= 480 msecs.

- Clinically significant uncontrolled arrhythmias Exception: subjects with
controlled atrial fibrillation for >30 days prior to day 1 of treatment with
GSK1120212 are eligible

- History of acute coronary syndromes (including myocardial infarction and
unstable angina), coronary angioplasty, or stenting within the past 24 weeks

- ≥Class II heart failure as defined by the New York Heart Association (NYHA)
functional classification system (see Appendix C)

- Known human immunodeficiency virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C
Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection
which will be allowed)

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to the study drug, dimethyl sulfoxide (DMSO), or excipients

- Psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol

- Any other concurrent condition that in the investigator's opinion would jeopardize
compliance with the protocol

Type of Study:


Study Design:

Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Outcome Measure:

the number and type of kinases in participant tissue sample prior to administration of drug compared to post-treatment.

Outcome Description:

use of pan kinase inhibitors immobilized on beads to capture expressed kinases in cells and tumors. The activation state of more than 60% of the expressed kinome, defined by RNA-seq, will be analyzed using mass spectrometry analysis of the captured kinases.

Outcome Time Frame:

Two years

Safety Issue:


Principal Investigator

Lisa Carey, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:

LCCC 1122



Start Date:

January 2012

Completion Date:

April 2014

Related Keywords:

  • Breast Cancer
  • GSK1120212
  • TNBC
  • Triple Negative Breast Cancer
  • Surgical Resection
  • Breast Neoplasms



Lineberger Comprehensive Cancer CenterChapel Hill, North Carolina  27599-7305