Ruxolitinib in Patients With Breast Cancer

Phase II Study of Ruxolitinib (INCB018424) in Patients With PSTAT3+ Breast Cancer

Ruxolitinib is a drug which blocks the Janus tyrosine Kinase (JAK) signaling pathway. It is thought that this pathway might be important in certain types of breast cancer, and that blocking this pathway might lead to anti-cancer effects. This study is testing the effects of ruxolitinib in patients with breast cancer.

Objectives:

Primary

• The primary objective of this two-stage, phase II study is to estimate the objective response rate to ruxolitinib in patients with metastatic or unresectable locally advanced breast cancer which is pStat3+ and which has progressed on at least one line of chemotherapy for advanced disease, and/or has recurred within 12 months of completion of neoadjuvant/adjuvant chemotherapy.

Secondary

• To describe the toxicity profile
• To evaluate clinical benefit rate (CR + PR + SD >/= 24 weeks)
• To estimate progression-free and overall survival

Exploratory

• To explore whether baseline hs-CRP level higher than the group median is associated with objective response
• To explore whether baseline IL-6 level higher than the group median is associated with objective response
• To describe hs-CRP level over time, and to describe the proportion of patients with a) hs-CRP > 3mg/L at baseline, on treatment, and at time of progression, and b) hs-CRP > 1mg/L at baseline, on treatment, and at time of progression
• To describe IL-6 level over time, and to describe the proportion of patients with IL-6 level above the upper limit of normal at baseline, on treatment, and at time of progression
• To describe pStat3 status by IHC in baseline metastatic biopsies
• To describe pStat3 status by IHC in on-study biopsies
• To describe pStat3 status by IHC in the time of progression biopsy samples
• To characterize archival and metastatic biopsy samples using triple immunofluorescence for CD44, CD24, and pStat3
• To characterize archival and metastatic biopsy samples using a previously characterized pStat3 gene signature
• To characterize circulating tumor cells (CTCs) for CD44, CD24, and pStat3 at baseline and time of progression

Inclusion Criteria:

• Histologically or cytologically confirmed invasive breast cancer
• Must have known ER, PR and HER2 status
• Either, Triple Negative Metastatic Breast Cancer or
• Inflammatory Breast Cancer with any ER, PR HER2 status
• Availability of archival tissue specimen suitable for pStat3 testing
• Life expectancy of greater than 3 months
• Measurable disease by RECIST
• At least one prior chemotherapy regimen for treatment of metastatic breast cancer and/or recurrence within 12 months of completion of neoadjuvant/adjuvant chemotherapy or
• For patients with inflammatory breast cancer but no distant metastases, progression through standard neoadjuvant chemotherapy is required

Exclusion Criteria:

• Pregnant or breastfeeding
• Active brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib
• Clinically significant malabsorption syndrome
• Concurrent use of medications/substances that are strong inhibitors of CY3A4
• No uncontrolled intercurrent illness