Defining the Triple Negative Breast Cancer Kinome Response to GSK1120212

NCT01467310 | Completed Early Phase 1 DMC FDA Drug

• 3 other identifiers: LCCC 112211-1689CA058223
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. This study is not intended to treat cancer, it is looking at ways that the investigators may treat cancer in the future.

Conditions

Breast Cancer

Keywords

GSK1120212; TNBC; Triple Negative Breast Cancer; Surgical Resection

Outcome Measures

Primary Outcomes (1)

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

  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.

  Two years

Secondary Outcomes (2)

• the number and type of kinases that produce a compensatory response to MEK inhibitor

  Two years

• the number of participants with adverse events

  Two years

Study Arms (1)

GSK1120212

EXPERIMENTAL

Drug: GSK1120212

Interventions

GSK1120212 DRUG

1.5 to 2.0 mg taken orally every day for seven days.

GSK1120212

Eligibility Criteria

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

You may qualify if:

• 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);

You may not qualify if:

• Pregnant or lactating female
• Currently active GI disease, or prior surgery that may affect ability to absorb oral medications
• 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 less.
• 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)

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• GlaxoSmithKline: collaborator
• National Cancer Institute (NCI): collaborator
• Susan G. Komen Breast Cancer Foundation: collaborator

Study Sites (1)

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

trametinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Lisa Carey, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2011
• First Posted: November 8, 2011
• Study Start: January 1, 2012
• Primary Completion: March 21, 2016
• Study Completion: March 21, 2016
• Last Updated: September 2, 2020

Record last verified: 2020-08

Locations

US (1)