NCT01594216

Ruxolitinib in Estrogen Receptor Positive Breast Cancer

A Phase II Trial Of The JAK-Inhibitor Ruxolitinib (INCB018424) In Combination With Exemestane For Patients With Estrogen Receptor (ER) Positive Advanced Breast Cancer)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Abramson Cancer Center at Penn Medicine · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase II investigator-Initiated trial of the Investigational Drug, Ruxolitinib, in combination with Exemestane in patients with estrogen-receptor positive advanced breast cancer. The objective of this study is to determine the preliminary safety and efficacy of the combination of exemestane and Ruxolitinib (INCB018424).

Detailed description

In vitro mechanisms link IL-6 to poor outcome in breast cancer via activated JAK/STAT tumor signaling, leading to an aggressive tumor phenotype, and our preliminary data support these mechanisms in women with ER+ disease. Our overarching hypotheses are that (1) IL-6 mediates upregulation of JAK/STAT signaling pathways that leads to poor prognosis in women with ER-positive disease, (2) blockade of JAK/STAT signaling, via JAK inhibition, in patients with activating IL-6 polymorphisms and/or upregulation of STAT3 tumor signaling will enhance the response to endocrine therapy, and (3) patients likely to respond to JAK inhibition can be identified by germline genotyping for IL-6 variants, and effectiveness of the targeted therapy will be measurable through tumor assessment of activated STAT signaling through upregulation of phospho- STAT3 and expression of STAT3 target genes. We now propose a trial to determine whether addition of the JAK inhibitor, Ruxolitinib (INCB018424), enhances the activity of exemestane alone in women with ER-positive breast cancer who have relapsed after non-steroidal aromatase inhibitor and carry a germline polymorphism in IL-6, and to determine if tumor activation of STAT3 can identify patients most likely to respond to the combination.

Conditions

• Estrogen-receptor Positive Invasive Metastatic Breast Cancer

Interventions

Type	Name	Description
DRUG	Ruxolitinib
DRUG	Exemestane

Timeline

• Start date: 2012-04-01
• Primary completion: 2016-04-01
• Completion: 2016-04-09
• First posted: 2012-05-09
• Last updated: 2024-06-12
• Results posted: 2024-06-12

Locations

1 site across 1 country: United States