Ruxolitinib in Combination With Trastuzumab in Metastatic HER2 Positive Breast Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02066532|
Recruitment Status : Active, not recruiting
First Posted : February 19, 2014
Last Update Posted : May 1, 2019
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Breast Cancer Breast Carcinoma HER-2 Positive Breast Cancer||Drug: Ruxolitinib Drug: Trastuzumab||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Trial of Ruxolitinib in Combination With Trastuzumab in Metastatic HER2 Positive Breast Cancer|
|Actual Study Start Date :||June 2014|
|Estimated Primary Completion Date :||November 2020|
|Estimated Study Completion Date :||December 2020|
Jakafi (Ruxolitinib) and Trastuzumab (Herceptin) - 21 day cycle until disease progression
25 mg 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: Jakafi
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
- Maximum Tolerated dose of Ruxolitinib in combination with Trastuzumab (Phase I) [ Time Frame: Up to 15 weeks ]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.
- Objective response rate [ Time Frame: Up to 24 weeks ]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 ]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)
- Prevalence of progression free survival (PFS) rate (Phase II) [ Time Frame: Up to 9 weeks ]Progression free survival (PFS) 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02066532
|United States, New York|
|Mount Sinai Medical Center|
|New York, New York, United States, 10029|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|New York Hospital-Weill Cornell Medical Center|
|New York, New York, United States, 10065|
|Montefiore Medical Center|
|New York, New York, United States, 10461|
|Principal Investigator:||Kevin Kalinsky, MD, MS||Columbia University|