Conditions: Estrogen-receptor Positive Invasive Metastatic Breast Cancer
Keywords: Postmenopausal female
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 25
Healthy volunteers: no

Brief 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.

Arms:
arm 1: Ruxolitinib at 25 mg orally, twice daily and Exemestane, 25 mg orally once daily arm 2: Ruxolitinib at 15 mg orally, twice daily and Exemestane, 25 mg orally once daily

Interventions: intervention 1: Ruxolitinib intervention 2: Exemestane
Intervention descriptions: intervention 1: None intervention 2: None

Protocol document: