Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

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

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

Ruxolitinib in Patients With Breast Cancer

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

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.

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 is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.

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.

Dana-Farber Cancer Institute

Principal Investigator

Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Ruxolitinib in Patients With Breast Cancer	NCT01562873	Breast Cancer	Ruxolitinib	18 Years -	Dana-Farber Cancer Institute
Ruxolitinib in Patients With Breast Cancer	NCT01562873	Breast Cancer	Ruxolitinib	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for pstat3+

Every month we try and update this database with for pstat3+ cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pstat3+

Every month we try and update this database with for pstat3+ cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pstat3+ cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.