Phase II study of combination ruxolitinib (INCB018424) with preoperative chemotherapy for triple negative inflammatory breast cancer (TBCRC039)
Johns Hopkins Kimmel Cancer Center in Baltimore
This research study is studying an investigational study drug called ruxolitinib as possible treatment for inflammatory breast cancer (IBC). 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. In this research study, we are evaluating ruxolitinib in combination with paclitaxel followed by the standard chemotherapy with doxorubicin and cyclophosphamide (also called adriamycin and cytoxan, (“AC”)). Paclitaxel (also called Taxol), doxorubicin and cyclophosphamide are FDA approved drugs for breast cancer patients. They have been shown to result in death of cancer cells when given as preoperative treatment of women with IBC. Laboratory studies have shown that ruxolitinib may make paclitaxel more effective.
1. Participants should have histologically confirmed triple-negative (estrogen/progesterone receptor and HER2 negative) invasive breast cancer.2. Participants must have the clinical diagnosis of inflammatory breast cancer.3. Participants should be 18 years or older and able to understand and willingness to sign a written consent form; males and females may be eligible.4. Eastern Cooperative Oncology Group Performance Status of 0 or 1.5. Normal organ and marrow function (adequate blood testing results).6. 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.7. 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.8. Adequate cardiac function.9. Women of child-bearing potential and men must agree to use adequate birth control methods.
Participants will be asked to undergo tumor biopsies at the beginning of treatment. Participants will be randomized to one of three groups: - Group 1 will receive ruxolitinib for 2 times per day for 7 days and then will receive paclitaxel (intravenous chemotherapy) for 12 weeks.Group 2 will receive ruxolitinib for 2 times per day for 7 days and then receive ruxolitinib and paclitaxel for 12 weeks.Grouyp 3 will receive ruxolitinib 2 times per day for 7 days and 1 dose of IV paclitaxel then receive daily ruxolitinib and paclitaxel for the next 11 weeks.Once the investigational treatment phase of the trial has been completed, patients will continue with standard of care treatment, with 4 cycles of doxorubicin and cyclophosphamide *intravenous chemotherapy). Following this standard chemotherapy, patients will undergo a modified radical mastectomy followed by radiation therapy.
01/17/2020 05:03 AM