This phase II trial studies how well trametinib and v-akt murine thymoma viral oncogene homolog 1 (Akt) inhibitor GSK2141795 work in treating patients with triple-negative breast cancer (breast cancer cells that do not have estrogen receptors, progesterone receptors, or large amounts of human epidermal growth factor receptor 2 \[HER2/neu\] protein) that has spread to other places in the body. Trametinib and Akt inhibitor GSK2141795 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To assess the anti-tumor activity associated with trametinib monotherapy in patients with triple negative breast cancer (TNBC). SECONDARY OBJECTIVES: I. To assess the anti-tumor activity associated with trametinib in combination with AKT inhibitor GSK2141795 after progression on trametinib in patients with metastatic TNBC. II. To determine the progression-free survival following the initiation of treatment with trametinib monotherapy in patients with metastatic TNBC. III. To determine the progression-free survival following the initiation of treatment with trametinib in combination with GSK2141795 in patients with metastatic TNBC. IV. To determine the overall survival following the initiation of treatment with trametinib with GSK214179 in patients with metastatic TNBC. V. To determine the nature and degree of toxicities associated with trametinib monotherapy and trametinib in combination with GSK2141795 in patients with metastatic TNBC. VI. To determine the biomarker potential of phosphatase and tensin homolog (PTEN) to predict response to single agent trametinib. VII. To determine molecular markers of sensitivity and resistance to trametinib monotherapy and trametinib in combination with GSK2141795 in patients with metastatic TNBC. OUTLINE: PART 1: Patients receive trametinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 52 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
Moffitt Cancer Center
Tampa, Florida, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Case Western Reserve University
Cleveland, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States
Objective Response Rate (ORR), Defined as the Proportion of Patients Who Have Had a Partial Response (PR) or Complete Response (CR) (RECIST 1.1 Based) Within the First 6 Months After Initiation of Therapy With Trametinib
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 6 months
Clinical Benefit Rate (CBR = CR+PR+Stable Disease [SD])
The clinical benefit rate (CR+PR+SD) will be reported for patients after Part 1 and after Part 2.
Time frame: Up to 52 weeks
Duration of Objective Response
Summary statistics of duration of response for patients with objective response
Time frame: up to 52 weeks
Incidence of Adverse Events That Are Classified as Either Possibly, Probably, or Definitely Related to Study Treatment
Incidence of adverse events for patients that are classified as either possibly, probably, or definitely related to study treatment graded by National Cancer Institute (NCI) CTCAE v4.0
Time frame: Up to 52 weeks
Incidence of Severe (Grade 3+) Adverse Events or Toxicities Graded Per NCI CTCAE Version 4.0
NCI CommonTerminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for grading incidence of toxicities (grade 3+).
Time frame: Up to 52 weeks
Overall Survival
The Kaplan-Meier method will be used to estimate overall survival distribution.
Time frame: Start date of the treatment to the date of the event (i.e., death) or the date of last follow-up to evaluate that event, assessed up to 52 weeks
Progression-free Survival
The Kaplan-Meier method will be used to estimate progression-free survival distribution.
Time frame: The duration of time from start of treatment to time of progression or death, whichever comes first, assessed up to 52 weeks
Proportion of Patients Who go Off Treatment Due to Adverse Reactions
The proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial was captured. These tolerability measures were assessed within each of the treatment parts independently. All patients who have received at least one dose of any of the therapeutic agents was evaluable for toxicity and tolerability.
Time frame: Up to 52 weeks
Proportion of Patients Who Refuse Further Treatment for Lesser Toxicities That Inhibit Their Willingness to Continue Participation on the Trial
Time frame: Up to 52 weeks
Tolerability of the Regimen Defined as the Number of Patients Who Required Dose Modifications and/or Dose Delays
Time frame: Up to 52 weeks
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