Alternative Drug Names:
Ruxolitinib (Jakafi brand in the US) was previously also known as INCB018242.
Purpose of Trial:
The purpose of this phase 1/2 study is 2-fold. In the first part of the study in metastatic breast cancer patients, the goal is to determine a safe dose of the investigational agent Ruxolitinib in combination with Paclitaxel. The second phase of the study, which is in newly diagnosed patients, to determine the effectiveness of this 2 drug combination followed by standard anthracycline chemotherapy in triple-negative IBC.
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 was presented at ASCO on this topic, and the abstract can be read here. Furthermore, inhibitors of JAK2 inhibit the growth of IBC tumors. This finding led to the study now ongoing to see if JAK2 inhibition can sensitize the IBC tumors to standard chemotherapy (paclitaxel) – i.e. 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.
This trial is for metastatic patients (part 1) or newly diagnosed triple-negative IBC patients (part 2). For metastatic patients enrolling part 1 of the study, no more than 2 prior chemotherapy regimens are allowed. Also, untreated or uncontrolled brain metastases are not allowed, but if they have been adequately treated and stable for >4 weeks, you are eligible. To be eligible, normal organ function and blood counts are required (see clinicaltrials.gov for detailed criteria for these). For the metastatic portion of the trial, there is a 2 week washout period – ie no chemotherapy or radiation is allowed in the 2 weeks preceding the trial initiation.
Ruxolitinib is an oral drug that will be taken twice a day (10mg each time) throughout treatment. Weekly clinic visits will be needed both for monitoring and receiving Paclitaxel, which will be given as a weekly infusion in this trial.
Weekly clinic visits will consist of physical examination, questions about side effects or other problems from the drugs, and blood tests (small sample taken). In terms of monitoring, you will receive CT or MRI scans to monitor the response of your tumor(s) every 2 cycles (6 weeks). Skin nodules or other visible tumors may be measured to evaluate response as well.
When the safe dose has been identified in the first part of the study, the metastatic portion will be closed. The neoadjuvant trial component will then begin. If you enroll in this portion of the trial, you will receive 1 week of ruxlitinib alone, followed by a research biopsy to assess biomarkers of response (for research). After this 1 week run-in period, 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.
Location of Trial:
Only at Dana Farber Cancer Institute in Boston, MA.
For more information:
Is this study NCI Compliant?:
NCT trial number & link:
NCT# 02041429 – click for more info
Poster from scientific meeting: