NCT02538471

LY2157299 Monohydrate (LY2157299) and Radiotherapy in Metastatic Breast Cancer

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: Weill Medical College of Cornell University · Academic / Other
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

Summary

Patients with metastatic breast cancer receiving at least one single agent chemotherapy and demonstrating stable disease or disease progression at two consecutive clinical/radiological assessments (at an interval of at least 2 weeks). Transforming growth factor-beta (TGFΒ) blockade will enhance response of irradiated tumors and improve the function of Dendritic and T cells. Patients will receive 300 mg/day of study drug administered via oral drug tablet every day for 14 days on and 14 days off (=28 day cycle). Radiation to a metastatic site will be delivered at a dose of 7.5 Gy, given consecutively on days 1-3-5.

Detailed description

Transforming growth factor-beta (TGFβ) is a pleiotropic cytokine which belongs to a superfamily of ligands, including bone morphogenetic proteins and activins \[1-5\]. Under normal conditions, members of the TGFβ family maintain homeostasis in many organ systems. In normal and non-cancerous cells, TGFβ limits the growth of epithelial, endothelial, neuronal, and hematopoietic cell lineages through anti-proliferative and apoptotic responses. In addition, TGFβ exerts potent effects that influence immune function, cell proliferation/ functional differentiation, cell adhesion, extracellular matrix production, cell motility, angiogenesis, and cytokine production. TGFβ has been implicated as an important factor in the growth, progression, and metastatic potential of advanced cancers. Although TGFβ has been shown to suppress the growth of epithelial cells in the early stages of tumor development (premalignant conditions), the effect on advanced cancers is more complex \[1, 5-6\]. Increased production of TGFβ has been found in many neoplasms such as breast, prostate, gastric, renal, and epidermal carcinomas, and elevated plasma TGFβ levels in patients have been correlated with advanced disease, metastases, and lower survival rates \[7-13\]. In these later stage cancers, TGFβ induced growth suppression is lost, and instead, TGFβ promotes tumor growth and metastasis. Eli Lilly has developed and produced a Transforming Growth Factor-beta (TGF-β) receptor type-1 kinase inhibitor. LY2157299 monohydrate (LY2157299) is a small molecule that inhibits the TGF-β receptor type 1 kinase activity. LY2157299 was developed to investigate its activity in patients with glioblastoma where TGF-β has been demonstrated to play a specific role in tumor progression. In addition, LY2157299 was investigated in other patient populations, either as a stand-alone therapy or in combination with standard anti-tumor treatment regimens for indications including hepatocellular carcinoma and pancreatic cancer. Future investigations include indications with likely TGF-β associated pathway activation, such as melanoma, breast and prostate cancer as well as hematologic malignancies.

Conditions

• Metastatic Breast Cancer

Interventions

Type	Name	Description
RADIATION	Radiation therapy	Imaging by PET/CT will be performed at baseline, 5 weeks and 15 weeks. The chosen metastatic sites will receive conformal external beam radiation 7.5 Gy/fraction x 3, to a total of 22.5 Gy over the course of one week.
DRUG	Study Drug	Patients will receive 300 mg/day of study drug administered via oral drug tablet every day for 14 days on and 14 days off (=28 day cycle) .

Timeline

• Start date: 2015-08-10
• Primary completion: 2018-09-04
• Completion: 2019-02-20
• First posted: 2015-09-02
• Last updated: 2019-12-09
• Results posted: 2019-12-09

Locations

1 site across 1 country: United States