Ruxolitinib in Patients With Breast Cancer

Phase 2

Terminated

Conditions: Breast Cancer

Interventions: Drug: Ruxolitinib

Registration Number: NCT01562873

Lead Sponsor: Dana-Farber Cancer Institute

Brief Summary: 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.

Detailed Description: 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

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 21

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ruxolitinib-Cohort A	Ruxolitinib	Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity. Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of \>/=5 by central testing or Cohort B - low positive status defined as a score of 3-4. Each cohort was evaluated with a 2 stage design. Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
Ruxolitinib-Cohort B	Ruxolitinib	Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity. Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of \>/=5 by central testing or Cohort B - low positive status defined as a score of 3-4. Each cohort was evaluated with a 2 stage design. Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).	The objective response rate (ORR) was defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival	Disease was evaluated radiologically every 8 weeks on treatment through 12 cycles and in long-term follow-up every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).	Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or equivocal progression of non-target lesions.
Clinical Benefit Rate	Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).	Clinical benefit rate (CBR) was defined as achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria. SD needed to be a minimum 24 weeks in duration.
Overall Survival	In long-term follow-up, patients were followed for survival every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).	Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.

Trial Locations

Locations (2): Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States