Galunisertib and Paclitaxel in Treating Patients With Metastatic Androgen Receptor Negative (AR-) Triple Negative Breast Cancer

Stage IV Breast Cancer Clinical Trial

Official title: A Phase Ib Trial of LY2157299 (TGFβR1 Kinase Inhibitor) With Paclitaxel in Patients With Triple Negative Metastatic Breast Cancer

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma
• Estrogen Receptor Negative
• HER2/Neu Negative
• Progesterone Receptor Negative
• Recurrent Breast Carcinoma
• Stage IV Breast Cancer
• Triple-Negative Breast Carcinoma

• NCT number: NCT02672475
• Study type: Interventional
• Source: Vanderbilt-Ingram Cancer Center
• Status: Completed
• Phase: Phase 1
• Start date: March 2016
• Completion date: August 2023