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Purpose

This study will determine the recommend dose of palbociclib in combination with letrozole and another medication, Ado-trastuzumab emtansine (T-DM1). Additionally, researchers will determine how well this recommended dose will improve outcomes in this type of advanced breast cancer. The study will include a safety lead-in with escalating dosing of palbociclib to determine the recommended phase II dose (RP2D) of palbociclib in this combination and an expanded phase II of palbociclib at the RP2D in combination with letrozole and Ado- trastuzumab Emtansine (T-DM1). The starting dose of palbociclib will be 75 milligrams (mg) by mouth (PO) daily for each 21 day cycle. If 0 of 3 patients at the 75mg dose level experience a dose limiting toxicity (DLT), the next 3 patients will be enrolled at the next higher dosing cohort of 100mg PO daily for each 21 day cycle. If 0 of 3 patients at the 100mg dose level experience a DLT, the next 3 patients will be enrolled at the next higher dosing cohort of 125mg PO daily for each 21 day cycle. If 0 of 3 patients at the 125mg dose level experience a DLT, 125mg PO daily of palbociclib will be the phase II recommended dose used in the phase II expanded cohort. Patients receiving the phase II recommended dose in phase I will be enrolled in phase II of the study. During safety lead-in and expanded phase II, Letrozole 2.5mg PO will be administered daily for each 21 day cycle and T-DM1 3.6 milligrams per kilograms intravenously (IV) will be administered on Day 1 of each 21 day cycle.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Female
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Pathologically confirmed diagnosis of Estrogen Receptor (ER) positive and HER2 (human epidermal growth factor receptor 2) positive metastatic breast cancer based on local laboratory results. - Prior treatment with a taxane (including paclitaxel, docetaxel and/or nanoparticle protein-bound paclitaxel). - Prior treatment with trastuzumab with or without pertuzumab. - Measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1. - Eastern Cooperative Oncology Group Performance Status of 0-2 - Adequate organ and marrow function - Women must be post-menopausal - Must be able to swallow pills

Exclusion Criteria

  • Current or anticipated use of other investigational agents - Prior therapy with a cyclin-dependent kinase 4/6 inhibitor - Subject has received chemotherapy or radiotherapy within 14 days prior to Cycle 1, Day 1 of the study or has not recovered from adverse events due to agents administered more than 14 days earlier - Subject has leptomeningeal disease - History of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib or other agents used in study - Subject has other illness or disease that the investigator believes will interfere with study requirements.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 1: Palbociclib 75 mg 		Palbociclib 75 milligrams (mg) by mouth (PO) daily Letrozole 2.5 mg PO Daily Ado-trastuzumab Emtansine (T-DM1) 3.6 milligrams per kilograms (mg/kg) intravenous (IV) Day 1
  • Drug: Palbociclib 75mg
    Oral Administration
    Other names:
    • Ibrance
  • Drug: Letrozole 2.5mg
    Oral Adminstration
    Other names:
    • Femara
  • Drug: T-DM1
    Intravenous Administration
    Other names:
    • Ado-trastuzumab Emtansine
    • Kadcyla
Experimental
Phase 1: Palbociclib 100 mg 		Palbociclib 100 milligrams (mg) by mouth (PO) daily Letrozole 2.5 mg PO Daily Ado-trastuzumab Emtansine (T-DM1) 3.6 milligrams per kilograms (mg/kg) intravenous (IV) Day 1
  • Drug: Letrozole 2.5mg
    Oral Adminstration
    Other names:
    • Femara
  • Drug: T-DM1
    Intravenous Administration
    Other names:
    • Ado-trastuzumab Emtansine
    • Kadcyla
  • Drug: Palbociclib 100mg
    Oral Administration
    Other names:
    • Ibrance
Experimental
Phase 1: Palbociclib 125 mg 		Palbociclib 125 milligrams (mg) by mouth (PO) daily Letrozole 2.5 mg PO Daily Ado-trastuzumab Emtansine (T-DM1) 3.6 milligrams per kilograms (mg/kg) intravenous (IV) Day 1
  • Drug: Letrozole 2.5mg
    Oral Adminstration
    Other names:
    • Femara
  • Drug: T-DM1
    Intravenous Administration
    Other names:
    • Ado-trastuzumab Emtansine
    • Kadcyla
  • Drug: Palbociclib 125mg
    Oral Administration
    Other names:
    • Ibrance
Experimental
Phase 2: RP2D 		Recommended Phase 2 dose (RP2D; determined during Phase 1 Safety Run In) Palbociclib by mouth (PO) daily Letrozole 2.5 mg PO Daily Ado-trastuzumab Emtansine (T-DM1) 3.6 milligrams per kilograms (mg/kg) intravenous (IV) Day 1
  • Drug: Letrozole 2.5mg
    Oral Adminstration
    Other names:
    • Femara
  • Drug: T-DM1
    Intravenous Administration
    Other names:
    • Ado-trastuzumab Emtansine
    • Kadcyla
  • Drug: Palbociclib
    Oral Administration
    Other names:
    • Ibrance

More Details

Status
Terminated
Sponsor
University of Kansas Medical Center

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.