T-DM1 with or without Palbociclib in Treating Patients with Metastatic HER2 Positive Breast Cancer

Status: Active


This phase II trial studies how well T-DM1 with or without palbociclib works in treating patients with HER2 positive breast cancer that has spread to other parts of the body. T-DM1 is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug called DM1. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers DM1 to kill them. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether T-DM1 with or without palbociclib may work better in treating patients with HER2 positive metastatic breast cancer.

Eligibility Criteria

Inclusion Criteria

  • 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).
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • 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 >= 10gm/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 upon discussion with the study principal investigator (PI).
  • No more than 2 lines of therapy in the metastatic disease setting.
  • Female subjects must be surgically sterile or be postmenopausal (defined as surgical removal of ovaries or no menses for 12 consecutive months or monthly gonadotrophin releasing hormone agonist use for ovarian suppression), 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.

Exclusion Criteria

  • HER2 negative tumors.
  • Prior treatment with T-DM1.
  • Prior treatment with CDK 4/6 inhibitors.
  • Known active 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).

Locations & Contacts


Banner University Medical Center - Tucson
Status: Active
Contact: Pavani Chalasani
Phone: 520-626-7725
Email: Pchalasani@uacc.arizona.edu
University of Arizona Cancer Center-North Campus
Status: Active
Contact: Pavani Chalasani
Phone: 520-626-7725
Email: Pchalasani@uacc.arizona.edu


University of Colorado Hospital
Status: Active
Contact: Peter Kabos
Phone: 303-724-4690
Email: peter.kabos@ucdenver.edu


New Haven
Yale University
Status: Active
Contact: Erin Wysong Hofstatter
Email: erin.hofstatter@yale.edu

New York

Roswell Park Cancer Institute
Status: Active
Contact: Mateusz Opyrchal
Email: Mateusz.Opyrchal@roswellpark.org


Thomas Jefferson University Hospital
Status: Active
Contact: Maysa M. Abu-Khalaf
Email: maysa.abu-khalaf@yale.edu


Swedish Medical Center-First Hill
Status: Active
Contact: Hank Kaplan
Email: Hank.Kaplan@swedish.org
University of Washington Medical Center
Status: Active
Contact: Jennifer Marie Specht
Phone: 206-606-6329
Email: jspecht@uw.edu


University of Wisconsin Hospital and Clinics
Status: Active
Contact: Kari Braun Wisinski
Email: kbwisinski@medicine.wisc.edu

Trial Objectives and Outline


I. Compare progression free survival of the combination arm trastuzumab emtansine (T-DM1) with palbociclib to single agent T-DM1.


I. Compare response rates between both treatment arms.

II. Compare overall survival between both treatment arms.


I. Investigate predictive biomarkers of response in blood and archived tumor tissue.

II. Investigate mechanisms of resistance for palbociclib in blood and tumor tissue.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive trastuzumab emtansine intravenously (IV) over 30-90 minutes on day 1 and palbociclib orally (PO) on days 5-18. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive trastuzumab emtansine IV over 30-90 minutes on day 1. Treatment 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 & Type

Trial Phase

Phase II

Trial Type


Lead Organization

Lead Organization
Banner University Medical Center - Tucson

Principal Investigator
Pavani Chalasani

Trial IDs

Primary ID 29747
Secondary IDs NCI-2018-01988
Clinicaltrials.gov ID NCT03530696