Inflammatory Breast Cancer (IBC)
Conditions
Keywords
Inflammatory Breast Cancer, Breast Cancer, Triple Negative Breast Cancer
Brief summary
This research study is studying Ruxolitinib as possible treatment for Inflammatory Breast Cancer (IBC). The Following drugs will be use in combination with Ruxolinitinib. * Paclitaxel (also called Taxol) * Doxorubicin also called Adriamycin * Cyclophosphamide, also called Cytoxan
Detailed description
This is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. The FDA (U.S. Food and Drug Administration) has not approved Ruxolitinib for Inflammatory Breast Cancer (IBC), but is has been approved for other uses. Ruxolitinib is a newly discovered drug that has been shown to block a pathway (called the IL6/JAK/Stat pathway) that may be important in cancer, including triple negative inflammatory breast cancer. Ruxolitinib brings proteins groups together, which can result in gene (DNA) changes. These DNA changes may stop cancer cells from growing. Paclitaxel (also called Taxol), Doxorubicin and Cyclophosphamide (also called Adriamycin and Cytoxan, ("AC")) are drugs FDA approved for breast cancer patients. They have been shown to result in death of cancer cells when given as preoperative treatment of women with inflammatory breast cancer (IBC). Laboratory studies have shown that Ruxolitinib may make Paclitaxel more effective. In this research study, the investigators are evaluating Ruxolitinib in combination with Paclitaxel followed by the standard chemotherapy, AC. Researchers will also evaluate how the IL6/JAK/Stat pathway is affected by this combination of drugs by studying biopsies and surgical specimens.
Interventions
DRUGRuxolitinib
15 or 20 mg, twice daily by mouth. The run-in part of ruxolitinib lasts 7 days; The treatment of ruxolitinib part lasts 12 weeks.
DRUGPaclitaxel
80 mg/m2, IV (in the vein) weekly for 12 weeks.
DRUGDoxorubicin
60 mg/m2, IV (in the vein) every 14 days for 4 doses.
DRUGCyclophosphamide
600 mg/m2, IV (in the vein) every 14 days for 4 doses.
Sponsors
Dana-Farber Cancer Institute
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have histologically confirmed invasive breast cancer. All histologic subtypes are eligible. * Patients must have known ER, PR, and HER2 status defined as triple-negative breast cancer (TNBC), defined as: --ER and PR \<10% by immunohistochemistry, and HER2-negative ( as per ASCO/CAP guidelines, defined as IHC 0 or 1+, or FISH ratio \<2.0 or HER2 copy number \<6.0). * Patients must have the clinical diagnosis of inflammatory breast cancer, involving an intact breast. * Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of ruxolitinib in participants \<18 years of age, children are excluded from this study. * ECOG performance status 0 or 1. * Participants must have normal organ and marrow function as defined below: * Leukocytes ≥ 3,000/mm3 * Absolute neutrophil count ≥ 1,500/mm3 * Platelets ≥ 100,000/mm3 * Bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) * AST (SGOT)/ALT (SGPT) \< 2.5 X institutional upper limit of normal * Creatinine ≤1.5 x institutional upper limit of normal OR creatinine clearance \> 60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal * Patients with evidence of extensive nodal involvement are allowed. Extensive nodal involvement is defined as metastatic disease involving any nodal region outside of the involved breast. * Patients with minimal metastatic disease involvement in bone or viscera are allowed. Minimal metastatic disease is defined as: evidence of metastatic involvement as demonstrated by imaging only, not amenable to biopsy confirmation. * Both men and women are allowed. * The effects of ruxolitinib on the developing human fetus are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry until completion of chemotherapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Ability to understand and the willingness to sign a written informed consent document. * LVEF \> 50% calculated by echocardiogram (ECHO) or MUGA * Patients may have bilateral breast cancer so long as one breast meets criteria for inflammatory breast cancer, and neither breast cancer has received prior therapy
Exclusion criteria
* Participants may not be receiving any other investigational agents. * Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib. * Participants receiving any medications or substances that are potent inhibitors of CYP3A4, including grapefruit juice are ineligible. Participants receiving fluconazole are also ineligible. (Please refer to Appendix B for the full list of potent inhibitors and washout periods). * Chronic corticosteroid use in excess of the equivalent of prednisone 10 mg once daily. * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant women are excluded from this study because paclitaxel, doxorubicin, and cyclophosphamide have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on study. These potential risks may also apply to other agents used in this study. * Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. * Known HIV-positive individuals on combination antiretroviral therapy are eligible so long as they meet all other criteria. Known HIV-positive individuals who are not on combination antiretroviral therapy are not eligible because these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated. * Clinically significant malabsorption syndrome. * Patients may not have received paclitaxel, doxorubicin, or cyclophosphamide as anti-neoplastic therapy. * Patients with prior radiation to the affected breast.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biologic Response To 7-Day Run-In Window Phase Treatment of Ruxolitinib Alone or Ruxolitinib Plus Paclitaxel | 7 days | Biologic response to 7-day run-in phase treatment, defined as a change in phosphorylated STAT3 (pSTAT3) expression from moderate/high positive (pSTAT3-positive) in pre-run-in phase sample to negative or weakly positive/equivocal (pSTAT3-negative) in post-run-in samples. pSTAT3 status was determined by evaluating the percent positive cells and the strength of staining (weak vs. strong/moderate) in relation to positive and negative controls. A T-score was calculated based on percent-stained cells and intensity of staining and interpreted as follows: Scores 0-4 are negative/weakly positive (pStat3 negative) and 5-8 are moderate/high positive (pStat3 positive). Hence, pStat3 negative indicates a biologic response or a decrease in pSTAT3 levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response Rate (pCR) After Preoperative Therapy | 28 weeks | Pathologic Complete Response rate (pCR) is defined as the absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative therapy. |
| Assess Change in STAT3 Gene Expression Following run-in Treatment | 7 Days | Change of STAT3 gene expression between pretreatment and post-ruxolitinib run-in (after 7 days of ruxolitinib alone or with one dose of weekly paclitaxel) biopsy specimens. RNA-seq was performed on a subset of tumor pairs (n=4 per run-in treatment group). Enrichment analysis for JAK-STAT and IL-6 Hallmark signatures obtained a Gene Set Variation Analysis (GSVA) enrichment score as a measure of STAT3 gene expression. The GSVA enrichment score is a continuous unitless measure that summarizes joint expression of multiple genes into a single value. A positive value indicates greater, and a negative value a lesser, enrichment of pathway signatures; thus a negative pre- to post-runin change in the value indicates a decrease in the STAT3 expression after the treatment, and a positive values indicates increase in STAT3 expression after treatment. |
| Determine Efficacy Defined as Disease-Free Survival (DFS) | 2 years | Disease-Free Survival (DFS) is defined as time of surgery, among the subset of patients who underwent surgery (n=21), until occurrence of recurrence, contralateral cancer, death attributable to any cause, second primary cancer other than breast. DFS was censored at date of last assessment. |
| Determine Efficacy Defined as Time to Treatment Failure (TTF) | 2 years | The endpoint is now more commonly known as event-free survival (EFS). Defined as time of treatment initiation until occurrence of recurrence, contralateral cancer, death attributable to any cause, second primary cancer other than breast or occurrence of progressive disease during preoperative therapy or treatment of disease that is not surgically resectable; otherwise censored at last disease follow-up. |
| Determine Efficacy Defined as Overall Survival (OS) | 2 years | Overall survival (OS) is defined as time from surgery until death from any cause or from treatment initiation until death from any cause. |
| Assess Residual Cancer Burden (RCB) Differences After Preoperative Therapy | 28 weeks | Residual cancer burden (RCB) is a continuous variable (RCB0 through RCB-IV) derived from the primary tumor dimensions, cellularity of the tumor bed, and axillary nodal burden as described in Symmans et al, 2007; where RCB-0 equals pathologic complete response (pCR) and considered the best prognosis and RCB-IV is considered the worst prognosis. |
| Changes in Interleukin 6 (IL-6) Plasma Levels During Treatment | 28 weeks | Elevations in interleukin (IL-6) and C-reactive protein (CRP) have been associated with worse clinical outcomes in patients with breast cancer. To determine whether STAT3 pathways were changed in the treatment groups, enrichment of JAKSTAT3 or IL-6 pathway-related gene signatures in the post-window phase samples compared to pre-window phase samples was analyzed. Enrichment analysis for JAK-STAT and IL-6 hallmark signatures were calculated using gene set variation analysis (GSVA) package. Each hospital followed their institutional guidelines for CRP and IL-6 measurements. |
| Changes in C-reactive Protein (CRP) Plasma Levels During Treatment | 28 weeks | Systemic biologic responses to ruxolitinib were assessed using serum IL-6 and c-reactive protein (CRP) levels. CRP levels are associated with poor prognosis and increased inflammatory response. Therefore, CRP levels in combination with pSTAT3 staining, could potentially be used as a more reliable method to select patients who would benefit from ruxolitinib treatment. To further analyze the effect of ruxolitinib throughout treatment, serum for CRP assessment was collected from patients at pre-window phase, post-window-phase, following 12-week neoadjuvant paclitaxel with or without ruxolitinib and immediately before surgery (pre-surgery). Each hospital followed their institutional guidelines for CRP measurements. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORFilipa Lynce, MD
Dana-Farber Cancer Institute
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ruxolitinib Alone First Patients (n=11) receiving ruxolitinib alone (15 mg or 20mg orally, depending on initial platelet count) given in the run-in treatment phase for 7 days. | 11 |
| Ruxolitinib Plus Paclitaxel First Patients (n=12) receive ruxolitinib (15 mg orally) twice daily for 7 days in combination with one dose of paclitaxel (80 mg/m2; administered on day 1, denoted Cycle 0, Day 1) in the run-in treatment phase for 7 days. | 12 |
| Total | 23 |
Baseline characteristics
| Characteristic | Ruxolitinib Alone First | Ruxolitinib Plus Paclitaxel First | Total |
|---|---|---|---|
| Age, Continuous Median Age, Window Phase | 54 years | 47 years | 53 years |
| Clinical N stage cN0 | 0 Participants | 1 Participants | 1 Participants |
| Clinical N stage cN1 | 10 Participants | 5 Participants | 15 Participants |
| Clinical N stage cN2 | 0 Participants | 2 Participants | 2 Participants |
| Clinical N stage cN3 | 0 Participants | 4 Participants | 4 Participants |
| Clinical N stage Unknown | 1 Participants | 0 Participants | 1 Participants |
| M stage M0 | 9 Participants | 11 Participants | 20 Participants |
| M stage M1 | 1 Participants | 0 Participants | 1 Participants |
| M stage Unknown | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Non-Hispanic | 11 Participants | 12 Participants | 23 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 12 Participants | 22 Participants |
| Region of Enrollment United States | 11 participants | 12 participants | 23 participants |
| Sex: Female, Male Female | 11 Participants | 12 Participants | 23 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 | 3 / 6 | 5 / 17 |
| other Total, other adverse events | 4 / 11 | 9 / 12 | 6 / 6 | 17 / 17 |
| serious Total, serious adverse events | 0 / 11 | 2 / 12 | 0 / 6 | 5 / 17 |
Outcome results
Primary
Biologic Response To 7-Day Run-In Window Phase Treatment of Ruxolitinib Alone or Ruxolitinib Plus Paclitaxel
Biologic response to 7-day run-in phase treatment, defined as a change in phosphorylated STAT3 (pSTAT3) expression from moderate/high positive (pSTAT3-positive) in pre-run-in phase sample to negative or weakly positive/equivocal (pSTAT3-negative) in post-run-in samples. pSTAT3 status was determined by evaluating the percent positive cells and the strength of staining (weak vs. strong/moderate) in relation to positive and negative controls. A T-score was calculated based on percent-stained cells and intensity of staining and interpreted as follows: Scores 0-4 are negative/weakly positive (pStat3 negative) and 5-8 are moderate/high positive (pStat3 positive). Hence, pStat3 negative indicates a biologic response or a decrease in pSTAT3 levels.
Time frame: 7 days
Population: A total of 23 patients were enrolled across 4 centers from January 24, 2018, to February 5, 2021. During the window phase of the trial, 11 patients received 7 days of ruxolitinib and 12 received ruxolitinib plus paclitaxel. Among 23 patients, 20 had baseline biopsy samples stained.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ruxolitinib Alone First | Biologic Response To 7-Day Run-In Window Phase Treatment of Ruxolitinib Alone or Ruxolitinib Plus Paclitaxel | pStat3 negative | 2 Participants |
| Ruxolitinib Alone First | Biologic Response To 7-Day Run-In Window Phase Treatment of Ruxolitinib Alone or Ruxolitinib Plus Paclitaxel | pStat3 positive | 9 Participants |
| Ruxolitinib Alone First | Biologic Response To 7-Day Run-In Window Phase Treatment of Ruxolitinib Alone or Ruxolitinib Plus Paclitaxel | Baseline pStat3 status not available | 0 Participants |
| Ruxolitinib Plus Paclitaxel First | Biologic Response To 7-Day Run-In Window Phase Treatment of Ruxolitinib Alone or Ruxolitinib Plus Paclitaxel | pStat3 negative | 3 Participants |
| Ruxolitinib Plus Paclitaxel First | Biologic Response To 7-Day Run-In Window Phase Treatment of Ruxolitinib Alone or Ruxolitinib Plus Paclitaxel | pStat3 positive | 6 Participants |
| Ruxolitinib Plus Paclitaxel First | Biologic Response To 7-Day Run-In Window Phase Treatment of Ruxolitinib Alone or Ruxolitinib Plus Paclitaxel | Baseline pStat3 status not available | 3 Participants |
Secondary
Assess Change in STAT3 Gene Expression Following run-in Treatment
Change of STAT3 gene expression between pretreatment and post-ruxolitinib run-in (after 7 days of ruxolitinib alone or with one dose of weekly paclitaxel) biopsy specimens. RNA-seq was performed on a subset of tumor pairs (n=4 per run-in treatment group). Enrichment analysis for JAK-STAT and IL-6 Hallmark signatures obtained a Gene Set Variation Analysis (GSVA) enrichment score as a measure of STAT3 gene expression. The GSVA enrichment score is a continuous unitless measure that summarizes joint expression of multiple genes into a single value. A positive value indicates greater, and a negative value a lesser, enrichment of pathway signatures; thus a negative pre- to post-runin change in the value indicates a decrease in the STAT3 expression after the treatment, and a positive values indicates increase in STAT3 expression after treatment.
Time frame: 7 Days
Population: To assess global transcriptomic changes during treatment, RNA-seq was performed on paired pre- and post-run-in phase tumor biopsy samples (n=4 per run-in treatment group).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ruxolitinib Alone First | Assess Change in STAT3 Gene Expression Following run-in Treatment | -0.06 GSVA enrichment score | Standard Deviation 0.23 |
| Ruxolitinib Plus Paclitaxel First | Assess Change in STAT3 Gene Expression Following run-in Treatment | 0.01 GSVA enrichment score | Standard Deviation 0.15 |
Secondary
Assess Residual Cancer Burden (RCB) Differences After Preoperative Therapy
Residual cancer burden (RCB) is a continuous variable (RCB0 through RCB-IV) derived from the primary tumor dimensions, cellularity of the tumor bed, and axillary nodal burden as described in Symmans et al, 2007; where RCB-0 equals pathologic complete response (pCR) and considered the best prognosis and RCB-IV is considered the worst prognosis.
Time frame: 28 weeks
Population: Subset (n=15, patients allocated to ruxolitinib plus paclitaxel given as neoadjuvant therapy) of the overall patient population allocated to ruxolitinib plus paclitaxel given as neoadjuvant therapy (n=17) who had tumor samples at both baseline and 28 wk timepoints.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ruxolitinib Alone First | Assess Residual Cancer Burden (RCB) Differences After Preoperative Therapy | RCB-0 (pCR) | 1 Participants |
| Ruxolitinib Alone First | Assess Residual Cancer Burden (RCB) Differences After Preoperative Therapy | RCB-I | 1 Participants |
| Ruxolitinib Alone First | Assess Residual Cancer Burden (RCB) Differences After Preoperative Therapy | RCB-II | 0 Participants |
| Ruxolitinib Alone First | Assess Residual Cancer Burden (RCB) Differences After Preoperative Therapy | RCB-III | 1 Participants |
| Ruxolitinib Alone First | Assess Residual Cancer Burden (RCB) Differences After Preoperative Therapy | RCB-IV | 3 Participants |
| Ruxolitinib Alone First | Assess Residual Cancer Burden (RCB) Differences After Preoperative Therapy | No surgery due to disease progression during neoadjuvant therapy | 0 Participants |
| Ruxolitinib Plus Paclitaxel First | Assess Residual Cancer Burden (RCB) Differences After Preoperative Therapy | RCB-IV | 9 Participants |
| Ruxolitinib Plus Paclitaxel First | Assess Residual Cancer Burden (RCB) Differences After Preoperative Therapy | RCB-0 (pCR) | 1 Participants |
| Ruxolitinib Plus Paclitaxel First | Assess Residual Cancer Burden (RCB) Differences After Preoperative Therapy | RCB-III | 2 Participants |
| Ruxolitinib Plus Paclitaxel First | Assess Residual Cancer Burden (RCB) Differences After Preoperative Therapy | RCB-I | 1 Participants |
| Ruxolitinib Plus Paclitaxel First | Assess Residual Cancer Burden (RCB) Differences After Preoperative Therapy | No surgery due to disease progression during neoadjuvant therapy | 2 Participants |
| Ruxolitinib Plus Paclitaxel First | Assess Residual Cancer Burden (RCB) Differences After Preoperative Therapy | RCB-II | 2 Participants |
Secondary
Changes in C-reactive Protein (CRP) Plasma Levels During Treatment
Systemic biologic responses to ruxolitinib were assessed using serum IL-6 and c-reactive protein (CRP) levels. CRP levels are associated with poor prognosis and increased inflammatory response. Therefore, CRP levels in combination with pSTAT3 staining, could potentially be used as a more reliable method to select patients who would benefit from ruxolitinib treatment. To further analyze the effect of ruxolitinib throughout treatment, serum for CRP assessment was collected from patients at pre-window phase, post-window-phase, following 12-week neoadjuvant paclitaxel with or without ruxolitinib and immediately before surgery (pre-surgery). Each hospital followed their institutional guidelines for CRP measurements.
Time frame: 28 weeks
Population: Subset (n=4, patients allocated to paclitaxel alone as neoadjuvant therapy; n=14, patients allocated to ruxolitinib plus paclitaxel given as neoadjuvant therapy) of the overall population allocated to neoadjuvant therapy (n=6; n=17, respectively) who had blood samples successfully assayed at both baseline and 28 wk timepoints.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ruxolitinib Alone First | Changes in C-reactive Protein (CRP) Plasma Levels During Treatment | -0.9 milligram per liter |
| Ruxolitinib Plus Paclitaxel First | Changes in C-reactive Protein (CRP) Plasma Levels During Treatment | 2.8 milligram per liter |
Secondary
Changes in Interleukin 6 (IL-6) Plasma Levels During Treatment
Elevations in interleukin (IL-6) and C-reactive protein (CRP) have been associated with worse clinical outcomes in patients with breast cancer. To determine whether STAT3 pathways were changed in the treatment groups, enrichment of JAKSTAT3 or IL-6 pathway-related gene signatures in the post-window phase samples compared to pre-window phase samples was analyzed. Enrichment analysis for JAK-STAT and IL-6 hallmark signatures were calculated using gene set variation analysis (GSVA) package. Each hospital followed their institutional guidelines for CRP and IL-6 measurements.
Time frame: 28 weeks
Population: Subset (n=4, patients allocated to paclitaxel alone as neoadjuvant therapy; n=13, patients allocated to ruxolitinib plus paclitaxel given as neoadjuvant therapy) of the overall population allocated to neoadjuvant therapy (n=6; n=17, respectively) who had blood samples successfully assayed at both baseline and 28 wk timepoints.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ruxolitinib Alone First | Changes in Interleukin 6 (IL-6) Plasma Levels During Treatment | 0.3 picograms per milliliter |
| Ruxolitinib Plus Paclitaxel First | Changes in Interleukin 6 (IL-6) Plasma Levels During Treatment | 1.6 picograms per milliliter |
Secondary
Determine Efficacy Defined as Disease-Free Survival (DFS)
Disease-Free Survival (DFS) is defined as time of surgery, among the subset of patients who underwent surgery (n=21), until occurrence of recurrence, contralateral cancer, death attributable to any cause, second primary cancer other than breast. DFS was censored at date of last assessment.
Time frame: 2 years
Population: Two patients whose disease progressed during neoadjuvant therapy did not have surgery; the other 21 patients proceeded to surgery and radiation therapy.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ruxolitinib Alone First | Determine Efficacy Defined as Disease-Free Survival (DFS) | DFS event - yes | 4 Participants |
| Ruxolitinib Alone First | Determine Efficacy Defined as Disease-Free Survival (DFS) | DFS event - no | 2 Participants |
| Ruxolitinib Plus Paclitaxel First | Determine Efficacy Defined as Disease-Free Survival (DFS) | DFS event - yes | 8 Participants |
| Ruxolitinib Plus Paclitaxel First | Determine Efficacy Defined as Disease-Free Survival (DFS) | DFS event - no | 7 Participants |
Secondary
Determine Efficacy Defined as Overall Survival (OS)
Overall survival (OS) is defined as time from surgery until death from any cause or from treatment initiation until death from any cause.
Time frame: 2 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ruxolitinib Alone First | Determine Efficacy Defined as Overall Survival (OS) | OS event - yes | 3 Participants |
| Ruxolitinib Alone First | Determine Efficacy Defined as Overall Survival (OS) | OS event - no | 3 Participants |
| Ruxolitinib Plus Paclitaxel First | Determine Efficacy Defined as Overall Survival (OS) | OS event - yes | 5 Participants |
| Ruxolitinib Plus Paclitaxel First | Determine Efficacy Defined as Overall Survival (OS) | OS event - no | 12 Participants |
Secondary
Determine Efficacy Defined as Time to Treatment Failure (TTF)
The endpoint is now more commonly known as event-free survival (EFS). Defined as time of treatment initiation until occurrence of recurrence, contralateral cancer, death attributable to any cause, second primary cancer other than breast or occurrence of progressive disease during preoperative therapy or treatment of disease that is not surgically resectable; otherwise censored at last disease follow-up.
Time frame: 2 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ruxolitinib Alone First | Determine Efficacy Defined as Time to Treatment Failure (TTF) | EFS event - yes | 4 Participants |
| Ruxolitinib Alone First | Determine Efficacy Defined as Time to Treatment Failure (TTF) | EFS event - no | 2 Participants |
| Ruxolitinib Plus Paclitaxel First | Determine Efficacy Defined as Time to Treatment Failure (TTF) | EFS event - yes | 10 Participants |
| Ruxolitinib Plus Paclitaxel First | Determine Efficacy Defined as Time to Treatment Failure (TTF) | EFS event - no | 7 Participants |
Secondary
Pathologic Complete Response Rate (pCR) After Preoperative Therapy
Pathologic Complete Response rate (pCR) is defined as the absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative therapy.
Time frame: 28 weeks
Population: Neoadjuvant treatment phase population including those who received single agent ruxolitinib during the window phase treatment and then proceeded to neoadjuvant therapy with daily ruxolitinib plus weekly paclitaxel for 12 weeks (n=5) and those patients who had received the combination of ruxolitinib plus paclitaxel during the window phase continued to receive it for a total of 12 weeks (n=12).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ruxolitinib Alone First | Pathologic Complete Response Rate (pCR) After Preoperative Therapy | pCR in breast and lymph nodes - No | 5 Participants |
| Ruxolitinib Alone First | Pathologic Complete Response Rate (pCR) After Preoperative Therapy | pCR in breast and lymph nodes - Yes | 1 Participants |
| Ruxolitinib Plus Paclitaxel First | Pathologic Complete Response Rate (pCR) After Preoperative Therapy | pCR in breast and lymph nodes - No | 16 Participants |
| Ruxolitinib Plus Paclitaxel First | Pathologic Complete Response Rate (pCR) After Preoperative Therapy | pCR in breast and lymph nodes - Yes | 1 Participants |