T-DM1 and Palbociclib in Treating Patients with Metastatic HER2 Positive Breast Cancer
- Be informed of the investigational nature of the study and all pertinent aspects of the trial.
- Sign and provide written consent in accordance with institutional and federal guidelines.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Recurrent or metastatic HER2-positive breast cancer (HER2 positivity is defined per American Society of Clinical Oncology-College of American Pathologists [ASCO-CAP] guidelines).
- Must have one of the following by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 * Measurable disease or * Evaluable disease
- Adequate cardiac reserve (left ventricular ejection fraction >= 50%).
- Serum creatinine =< 1.5 x institutional upper limit of normal (IULN).
- Bilirubin =< 2.0.
- Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (SGPT)/alkaline phosphatase =< 2.0 x IULN.
- Absolute neutrophil count (ANC) >= 1000.
- Platelets >= 100,000/ml.
- Hemoglobin >= 10 gm/dL.
- Be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures.
- Been treated with pertuzumab previously (neoadjuvant or metastatic setting). Patients who weren’t able to tolerate pertuzumab due to side effects can be eligible for study.
- No more than 2 lines of therapy in the metastatic disease setting.
- Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment and must agree to use effective contraception during the period of therapy. Women of childbearing potential and men should use effective methods of contraception during the entire duration on study and for 7 months after completion.
- HER2 negative tumors.
- Prior treatment with T-DM1 in the metastatic setting. If treated with prior T-DM1 in the neoadjuvant or adjuvant setting, a treatment free interval of at least 12 months.
- Prior treatment with CDK 4/6 inhibitors.
- Known active symptomatic central nervous system (CNS) metastases or carcinomatous meningitis. Patients with stable CNS metastases including brain metastases who have completed a course of radiotherapy are eligible for the study provided they are clinically stable. However, oral corticosteroids for control of CNS symptoms are not allowed on study.
- Known documented or suspected hypersensitivity to the components of the study drug(s) or analogs.
- Uncontrolled systemic illness, including but not limited to ongoing or active infection.
- Symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months.
- Be pregnant or breast feeding.
- Concurrent endocrine therapy or other anti-neoplastic therapy is not allowed. Patients can receive supportive therapy like bone-directed therapy including bisphosphonates or denosumab. Other supportive care medications can be used if clinically indicated (like growth factor support). If a patient is on GnRH (gonadotrophin releasing hormone) agonist for ovarian suppression, they can continue it. If a patient is already on a Gonadotrophin releasing hormone agonists, it can be continued during this study.
I. Estimate progression free survival of trastuzumab emtansine (T-DM1) + palbociclib.
I. Estimate response rates of T-DM1 + palbociclib treatment regimen.
II. Estimate overall survival of T-DM1+ palbociclib treatment regimen.
I. Investigate predictive biomarkers of response in blood and archived tumor tissue.
II. Investigate mechanisms of resistance for palbociclib in blood and tumor tissue.
Patients receive trastuzumab emtansine intravenously (IV) over 30-90 minutes on day 1 and palbociclib orally (PO) on days 5-18. Cycles repeats every 21 days in the absence of disease progression or unacceptable toxicity.
After conclusion of study treatment, patients are followed up at 30 days and then every 6 months.
Trial Phase Phase II
Trial Type Treatment
Banner University Medical Center - Tucson
- Primary ID 29747
- Secondary IDs NCI-2018-01988
- Clinicaltrials.gov ID NCT03530696