Phase I/II Trial of Ruxolitinib in Combination With Trastuzumab in Metastatic HER2 Positive Breast Cancer
The purpose of this study is to examine the safety and efficacy of Ruxolitinib in combination with Trastuzumab in treatment of HER2 positive metastatic breast cancer. Ruxolitinib (Jakafi) is an Food and Drug Administration (FDA) approved treatment for myelofibrosis (a disease of the bone marrow), but its safety and efficacy in breast cancer patients is not known. Trastuzumab (Herceptin) is an FDA-approved treatment for HER2 positive breast cancer. The safety and efficacy of both treatments given in combination is not known. It is hypothesized that Ruxolitinib in combination with Trastuzumab will demonstrate efficacy in treating Metastatic HER2 Positive Breast Cancer subjects, and will have a tolerable safety profile in this patient population.
Metastatic Breast Cancer
HER-2 Positive Breast Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Trial of Ruxolitinib in Combination With Trastuzumab in Metastatic HER2 Positive Breast Cancer|
- Phase I- Maximum Tolerated dose of Ruxolitinib in combination with Trastuzumab [ Time Frame: Up to 15 weeks ] [ Designated as safety issue: Yes ]The maximum tolerated dose (MTD) combination is defined as the dose combination associated with a target probability of dose limiting toxicity (DLT) of 0.25. A dose-limiting toxicity is defined as the MTD with DLTs defined as any grade 3 non-hematologic toxicities despite maximal supportive care or any grade 4 hematologic toxicity. The MTD will be estimated using the time to event continual reassessment method (TITE-CRM). The TITE-CRM will use an empirical dose-toxicity model, with a sample size of 10. The dose-toxicity model is calibrated such that the method will eventually select a dose that yields between 16%% and 34% DLT.
- Phase II- Progression free survival (PFS) [ Time Frame: Up to 9 weeks ] [ Designated as safety issue: No ]Progression free survival (PFS) of the combination of ruxolitinib plus trastuzumab in patients with HER2+ metastatic breast cancer who have previously received HER2 targeted therapy will be measured every 3 cycles (9 weeks of treatment +/- 4 days). PFS will be defined as the time from patient registration until objective or disease progression or death from any cause. This will be assessed via Response Evaluation Criteria In Solid Tumors (RECIST) criteria, in which tumor size measurements are compared to baseline from computed tomography (CT)/magnetic resonance imaging (MRI) scans at sequential intervals indicated in the time frame above.
- Objective Response Rate [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]Participants will be reviewed at 24 weeks to determine the objective response rate, which is defined as the percent of participants who are progression-free at 24 weeks.
- Number of participants with adverse events [ Time Frame: Up to 30 days of the last dose of treatment ] [ Designated as safety issue: Yes ]All patients will be evaluated for toxicity from the time of their first treatment with the study drugs. The frequency of subjects experiencing toxicities will be tabulated using the Canter Therapies Evaluation Program (CTEP) Active Version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE 4.0)
|Study Start Date:||June 2014|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||June 2017 (Final data collection date for primary outcome measure)|
Experimental: Ruxolitinib in Combination with Trastuzumab
Jakafi (Ruxolitinib), 25mg bid, 20mg bid, 15 mg bid, or 10mg bid, days 1-21 of a 21 days cycle, until disease progression Trastuzumab (Herceptin) 8mg/kg, 6 mg/kg, day 1 of a 21 cycle until disease progression
25mg bid, 20 mg bid, 15 mg bid, or 10 mg bid, (oral, twice a day) on days 1 through 21 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops
Other Name: JakafiDrug: Trastuzumab
6 mg/kg every 3 weeks (cycle = 21 days). If no trastuzumab > 28 days, patients will be initially re-loaded at 8 mg/kg, then 6 mg/kg.
Other Name: Herceptin
Breast cancer is the most common female cancer and the second most common cause of cancer death in women. Approximately 1,150,000 cases and 410,000 deaths from breast cancer occur annually worldwide, and, in the U.S., there are an estimated 184,450 new cases and 40,480 deaths from breast cancer every year. The vast majority of patients who die from breast cancer succumb to metastatic disease. The human epidermal growth factor receptor type 2 gene (HER2) is amplified in 20% to 30% of breast cancers.
HER2+ breast cancers are associated with earlier recurrence and shorter overall survival and are associated with other adverse prognostic markers, such as high tumor grade, high rates of cell proliferation, increased nodal metastases, and relative resistance to certain types of chemotherapy. The HER family of receptors is a group of related transmembrane receptor tyrosine kinases that regulate normal cell survival, proliferation, differentiation, and migration.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02066532
|Contact: Kevin Kalinsky, MD, MS||212-305-1945||KK2693@cumc.columbia.edu|
|United States, New York|
|Mount Sinai Medical Center||Recruiting|
|New York, New York, United States, 10029|
|Contact: Amy Tiersten, MD 212-241-2299 firstname.lastname@example.org|
|Principal Investigator: Amy Tiersten, MD|
|Columbia University Medical Center||Recruiting|
|New York City, New York, United States, 10032|
|Contact: Kevin Kalinsky, MD, MS 212-305-1945 KK2693@cumc.columbia.edu|
|Contact: Dan Otap, CCRP 212-342-3970 DO2267@cumc.columbia.edu|
|Principal Investigator: Kevin 1 Kalinsky, MD, MS|
|Principal Investigator:||Kevin Kalinsky, MD, MS||Columbia University|