This phase I trial studies the side effects and best dose of Galunisertib when given together with paclitaxel in treating patients with androgen receptor negative or triple negative breast cancer that has spread to other places in the body. Some tumors need growth factors, which are made by the body's white blood cells, to keep growing. Galunisertib may interfere with growth factors and help cause tumor cells to die. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving Galunisertib together with paclitaxel may kill more tumor cells.
PRIMARY OBJECTIVES: I. To assess the safety and tolerability of paclitaxel when administered with LY2157299 (Galunisertib). II. To determine the maximally tolerated dose (MTD) of paclitaxel + LY2157299. III. To determine the recommended dose of paclitaxel with LY2157299 for phase II studies. SECONDARY OBJECTIVES: I. To evaluate the efficacy, as measured by median progression free survival (PFS), of paclitaxel + LY2157299 in patients with metastatic androgen receptor negative triple negative metastatic breast cancer. II. To evaluate the efficacy, as measured by clinical benefit rate (CBR), of paclitaxel + LY2157299 in patients with androgen receptor negative metastatic triple negative metastatic breast cancer. III. To determine the overall response rate (ORR) of paclitaxel + LY2157299 in patients with androgen receptor negative metastatic triple negative breast cancer. TERTIARY OBJECTIVES: I. To interrogate the entire coding sequence of 236 cancer-related genes (3,769 exons) plus 47 introns from 19 genes often rearranged or altered in cancer. II. Nanostring analysis of established gene expression signatures. III. Determine breast cancer subtype by PAM50 testing and correlate with response. IV. To measure changes in circulating plasma transforming growth factor beta 1 (TGFB1), interleukin (IL)-6, and cluster of differentiation 34 (CD34) positive (+), peripheral blood mononuclear cells (PBMCs) induced by LY2157299. OUTLINE: This is a dose-escalation study of Galunisertib. Patients receive paclitaxel intravenously (IV) on days 1, 8, and 15. Patients also receive Galunisertib orally (PO) twice daily (BID) on days 1-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
Incidence of adverse events
Adverse events will be classified by type, incidence, severity and causality. All adverse events will be summarized by patient and dose level.of galunisertib in combination with paclitaxel graded by National Cancer Institute Common Terminology Criteria For Adverse Events (NCI CTCAE) version 4.03
Time frame: Up to 28 days after last dose of study treatment
Maximum Tolerated Dose (MTD) of paclitaxel + LY2157299
MTD is defined as the highest dose tested in which a dose limiting toxicity is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels galunisertib in combination with paclitaxel graded by NCI CTCAE version 4.03
Time frame: Up to 28 days
Overall Response Rate (ORR)
Number of patients in each response category, per RECIST v1.1, summarized as follows for target lesion criteria complete response (CR),disappearance of target lesions; partial response (PR), \>=30% decrease in sum of longest diameter of target lesions; progressive disease (PD), \>=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or SD. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR\>PR\>SD\>PD.
Time frame: On-treatment date to date of disease progression, assessed up to 3 years
Progression-Free Survival (PFS)
Estimated probable duration of life without disease progression, from on-study date to earlier of progression date or date of death from any cause, using the Kaplan-Meier method with censoring. Disease progression is defined under RECIST v1.1 as \>=20% increase in sum of longest diameters of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions.
Time frame: On-study date to lesser of date of progression or date of death from any cause, assessed up to 3 years
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