Alternative Drug Names:
Ruxolitinib (Jakafi brand in the US) was previously also known as INCB018242. Paclitaxel is often shortened as “taxol”. “AC” is short for adriamycin and cyclophosphamide. Doxorubicin is another name for Adriamycin. Cyclophosphamide may also be called Cytoxan (brand name).
Purpose of Trial:
The purpose of this trial is to determine whether the new drug Ruxolitinib improves the efficacy of a type of standard chemotherapy treatment in triple negative IBC (the taxol-AC regimen). Both efficacy and safety will be monitored, and a biopsy after 7 days of Ruxolitinib alone will be used to determine the effectiveness of this drug in inhibiting its target (JAK2-STAT3 signaling).
Why this study is relevant for IBC patients:
Ruxolitinib is an inhibitor of the JAK2-STAT3 pathway which regulates cell division and cell growth in many cancers. In preclinical work directly relevant to IBC, it has been shown that IBC stem cells, which are the treatment-resistant cells that cause metastasis, have high levels of JAK2 and downstream pathway activation. A study that was presented at ASCO on this topic, and the abstract can be read here (https://meetinglibrary.asco.org/record/81489/abstract). Furthermore, inhibitors of JAK2 inhibit the growth of IBC tumors. This finding led to a previous study to find the right dose of Ruxolitinib along with paclitaxel. This current trial builds on that trial to determine whether JAK2 inhibition can sensitize the IBC tumors to standard chemotherapy (paclitaxel) i.e. by targeting both the stem cells and proliferating cells at once.
Ruxolitinib is a JAK1 and JAK2 inhibitor that has been FDA-approved for the treatment of myelofibrosis, a type of blood cancer characterized by JAK2 activating mutations, and more recently polycythemia vera. In these populations, who are largely patients 60 and above, the drug is well tolerated. The main serious side effects include anemia and low platelet counts. A short scientific review paper about the pathway is here. In terms of the chemotherapy portion of the treatment, paclitaxel is an anti-mitotic chemotherapy that has been approved for breast cancer treatment for many years. “AC” is a standard anthracycline-containing regimen used in breast cancers including IBC. It can be given either every 3 weeks or every 2 weeks (known as dose-dense).
This is a phase II trial for newly diagnosed triple-negative IBC that remains localized to the breast and regional lymph nodes. Triple negative is defined as less than 10% ER and PR and HER2 negative by standard ASCO/CAP guidelines. To be eligible, normal organ function and blood counts are required (see clinicaltrials.gov for detailed criteria for these). You must agree to an upfront research biopsy and a follow up biopsy after 7 days of Ruxolitinib.
Ruxolitinib is an oral drug that will be taken twice a day (15 or 20mg each time) for 1 week. After this 1 week run-in period and second biopsy, you will then receive 12 weeks of Paclitaxel and Ruxolitinib, followed by 4 doses of Adriamycin and Cyclophosphamide (Cytoxan) as would be standard treatment for triple negative IBC in a dose-dense approach (every 2 weeks). If you have responded sufficiently to the 21 weeks of chemotherapy, then you will proceed to surgery and radiation as is standard care for IBC. Weekly clinic visits will be needed both for monitoring and receiving Paclitaxel, which will be given as a weekly infusion in this trial. In the “AC” portion you will only have to visit every 2 weeks. Clinic visits will consist of physical examination, questions about side effects or other problems from the drugs, and blood tests (small sample taken).
Location of Trial:
The trial is open at 2 sites – one is Dana Farber Cancer Institute in Boston, MA and the other is the University of Michigan in Ann Arbor (both are NCI comprehensive cancer centers).
For more information:
For the Michigan site, contact the principal investigator Dr Catherine Van Poznak at cv*****@me*.edu..
Is this study NCI Compliant?:
NCT trial number & link:
NCT02876302 click for more info
Poster from scientific meeting: