Clinical Trial: Study Of Ruxolitinib (INCB018424) With Preoperative Chemotherapy For Triple Negative Inflammatory Breast Cancer

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase II Study Of Combination Ruxolitinib (INCB018424) With Preoperative Chemotherapy For Triple Negative Inflammatory 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 Summary:

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.

Sponsor: Dana-Farber Cancer Institute

Current Primary Outcome: Assess JAK Inhibition With Ruxolitinib On pStat3+ Expression [ Time Frame: 7 days ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Determine Pathologic Complete Response rate (pCR) after preoperative therapy [ Time Frame: 28 weeks ]
  pCR defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative therapy.
• Correlate effects on pSTAT3+ and STAT3 gene expression with pCR [ Time Frame: 28 weeks ]
  assess pSTAT level and gene expression on pre-treatment tumor biopsy specimens and correlate expression with pCR
• Assess changes in pSTAT3 level and STAT3 gene expression following treatment [ Time Frame: 28 weeks ]
  assess pSTAT level and gene expression on pre-treatment tumor biopsy
• Asses difference in pCR rate following preoperative treatment [ Time Frame: 28 weeks ]
  pCR defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative therapy.
• Determine efficacy defined as Disease-Free Survival (DFS) [ Time Frame: 5 years ]
  Defined as time of surgery until occurrence of recurrence, contralateral cancer, death attributable to any cause, second primary cancer other than breast.
• Determine efficacy defined as Time to Treatment Failure (TTF) [ Time Frame: 5 years ]
  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.
• Determine efficacy defined as Overall Survival (OS) [ Time Frame: 5 years ]
  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 [ Time Frame: 5 years ]
  Difference between combination ruxolitinib with paclitaxel or paclitaxel alone followed by doxorubicin/cyclophosphamide; RCB defined by Symmans et al
• Describe changes in IL-6 plasma levels during treatment [ Time Frame: 5 years ]
  IL-6 levels will be recorded in the case report forms.
• Describe changes in CRP plasma levels during treatment [ Time Frame: 5 years ]
  CRP levels will be recorded in the case report forms.
• Assess distribution of CD44+/CD24- stem cell population in tumor pre- and post-exposure to ruxolotinib [ Time Frame: 5 years ]
  Performed on breast biopsies and residual disease in mastectomy specimens
• Assess pSTAT level and STAT3gene expression when ruxolitinib is withdrawn [ Time Frame: 5 years ]
  assess pSTAT level and gene expression on pre-treatment tumor biopsy specimen, run-in biopsy specimen, and any residual tumor at time of surgical resection
• Asses pSTAT3 level and STAT3 gene expression after combination ruxolitinib with paclitaxel [ Time Frame: 5 years ]
  assess pSTAT level and gene expression on tumor biopsy specimens

Original Secondary Outcome:

• Determine Pathologic Complete Response rate (pCR) after preoperative therapy [ Time Frame: 28 weeks ]
  pCR defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative therapy.
• Correlate effects on pSTAT3+ and STAT3 gene expression with pCR [ Time Frame: 28 weeks ]
  assess pSTAT level and gene expression on pre-treatment tumor biopsy specimens and correlate expression with pCR
• Assess changes in pSTAT3 level and STAT3 gene expression following treatment [ Time Frame: 28 weeks ]
  assess pSTAT level and gene expression on pre-treatment tumor biopsy
• Asses difference in pCR rate following preoperative treatment [ Time Frame: 28 weeks ]
  pCR defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative therapy.
• Determine efficacy defined as Disease-Free Survival (DFS) [ Time Frame: 5 years ]
  Defined as time of surgery until occurrence of recurrence, contralateral cancer, death attributable to any cause, second primary cancer other than breast.
• Determine efficacy defined as Time to Treatment Failure (TTF) [ Time Frame: 5 years ]
  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.
• Determine efficacy defined as Overall Survival (OS) [ Time Frame: 5 years ]
  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 [ Time Frame: 5 years ]
• Describe changes in IL-6 plasma levels during treatment [ Time Frame: 5 years ]
  IL-6 levels will be recorded in the case report forms.
• Describe changes in CRP plasma levels during treatment [ Time Frame: 5 years ]
  CRP levels will be recorded in the case report forms.
• Assess distribution of CD44+/CD24- stem cell population in tumor pre- and post-exposure to ruxolotinib [ Time Frame: 5 years ]
  Performed on breast biopsies and residual disease in mastectomy specimens
• Assess pSTAT level and STAT3gene expression when ruxolitinib is withdrawn [ Time Frame: 5 years ]
  assess pSTAT level and gene expression on pre-treatment tumor biopsy specimen, run-in biopsy specimen, and any residual tumor at time of surgical resection
• Asses pSTAT3 level and STAT3 gene expression after combination ruxolitinib with paclitaxel [ Time Frame: 5 years ]
  assess pSTAT level and gene expression on tumor biopsy specimens

Information By: Dana-Farber Cancer Institute

Dates:
Date Received: August 9, 2016
Date Started: April 26, 2017
Date Completion: February 2024
Last Updated: April 27, 2017
Last Verified: April 2017