This phase Ib/II tests the safety, side effects, and best dose of icosapent ethyl in combination with dasatinib and whether they work to shrink tumors in patients with triple-negative inflammatory breast cancer that has spread to other places in the body (metastatic). Triple-negative inflammatory breast cancer is a type of inflammatory breast cancer in which the tumor cells do not have estrogen receptors, progesterone receptors, or large amounts of HER2/neu protein on their surface. Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Icosapent ethyl is an omega-3 fatty acid and in a class of medications called antilipemic or lipid-regulating agents. It may decrease the amount of triglycerides and other fats made in the liver. Preclinical studies have suggested that it may reduce the growth of triple negative inflammatory breast cancer cells. Combination therapy with dasatinib and icosapent ethyl may help shrink tumors in patients with triple-negative inflammatory breast cancer.
PRIMARY OBJECTIVES: I. To determine maximum tolerated dose (MTD) of icosapent ethyl (EPA) and dasatinib in patients with metastatic triple negative inflammatory breast cancer (mTN-IBC). (Phase 1b) II. To determine the overall response rate (ORR) of EPA and dasatinib therapy in patients with mTN-IBC. (Phase 2) SECONDARY OBJECTIVES: I. To determine the clinical benefit rate (CBR) of EPA and dasatinib therapy in patients with mTN-IBC. II. To determine progression-free survival (PFS) at 1 year for patients with mTN-IBC who were enrolled in the study and received EPA and dasatinib therapy. III. To determine overall survival (OS) at 2 years for patients with mTN-IBC who were enrolled in the study and received EPA and dasatinib therapy. IV. To determine the induction of apoptosis by EPA and dasatinib therapy. EXPLORATORY OBJECTIVES: I. To determine the effect of EPA and dasatinib therapy on the expression of cholesterol transporter. II. To determine the relationship between the expression of EphA2 and the treatment response to EPA and dasatinib therapy. III. To determine the change in Ki67 by EPA and dasatinib therapy. IV. To evaluate the change in cholesterol homeostasis and tumor membrane rigidity after EPA and dasatinib therapy. V. To investigate the effect of EPA and dasatinib therapy on the systemic inflammation. OUTLINE: This is a phase Ib dose-escalation study of icosapent ethyl in combination with fixed dose dasatinib, followed by a phase II study. Patients receive icosapent ethyl orally (PO) twice daily (BID) and dasatinib PO once daily (QD) in each treatment cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of the study treatment, patients will undergo in-clinic post-treatment evaluations 1 month after their last study treatment or before starting new treatment, whichever occurs first, subsequently, patients are followed every 3 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
1
Given PO
Given PO
M D Anderson Cancer Center
Houston, Texas, United States
Maximum Tolerated Dose (MTD) for Dasatinib and Icosapent Ethyl (EPA) Combination Therapy (Phase 1b)
MTD is selected based on isotonic regression. Specifically, the dose is selected as the MTD for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate. If there are ties, the higher dose level is selected when the isotonic estimate is lower than the target toxicity rate; the lower dose level is selected when the isotonic estimate is greater than or equal to the target toxicity rate.
Time frame: Up to 2 years
Overall Response Rate (ORR) of Dasatinib and EPA Combination Therapy (Phase 2)
the percentage of patients with a best overall response of CR (complete response) or PR (partial response)
Time frame: Up to 2 years
Clinical Benefit Rate (CBR)
Will be the proportion of the patients with static disease (SD) \>= 24 weeks, complete response (CR), and partial response (PR). CBR will be estimated along with a 95% exact confidence interval.
Time frame: Up to 2 years
Progression-free Survival
Defined as the rate of patients without the progression of disease or loss to follow-up at 1 year after initiating the EPA and dasatinib combination therapy. Will be estimated using the methods of Kaplan and Meier.
Time frame: At 1 year
Overall Survival
Defined as the survival rate at 2 years after initiating the EPA and dasatinib combination therapy. Will be estimated using the methods of Kaplan and Meier.
Time frame: At 2 years
Induction of Tumor Apoptosis
Tumor apoptosis will be measured by using the Luminex Apoptosis multiplex immunoassay panel (cleaved caspase-3) as well as TdT-Mediated dUTP Nick End Labeling (TUNEL) assay.
Time frame: After cycle 2 (1 cycle = 28 days)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.