Palbociclib in Estrogen Receptor Positive (ER+) Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Metastatic Breast Cancer

A Phase I/II Study of Palbociclib, Letrozole and T-DM1 in Trastuzumab Refractory Estrogen Receptor Positive (ER+) and HER2 Positive Metastatic Breast Cancer

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.

Study Overview

• Status: Terminated
• Conditions: HER2-positive Breast Cancer; Breast Cancer Metastatic
• Intervention / Treatment: Drug: Palbociclib 75mg; Drug: Letrozole 2.5mg; Drug: T-DM1; Drug: Palbociclib 100mg; Drug: Palbociclib 125mg; Drug: Palbociclib

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66205
      • The University of Kansas Cancer Center, Westwood Campus
    • Kansas City, Kansas, United States, 66112
      • The University of Kansas Cancer Center, West Clinic
    • Overland Park, Kansas, United States, 66210
      • The University of Kansas Cancer Center, Overland Park Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64154
      • The University of Kansas Cancer Center, North Clinic
    • Lee's Summit, Missouri, United States, 64064
      • The University of Kansas Cancer Center, Lee's Summit Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Kadcyla; Ado-trastuzumab Emtansine
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: Kadcyla; Ado-trastuzumab Emtansine; 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: Kadcyla; Ado-trastuzumab Emtansine; 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: Kadcyla; Ado-trastuzumab Emtansine; Drug: Palbociclib; Oral Administration; Other Names: Ibrance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Overall Response	Determine overall response rate (ORR), defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	From the time of first documented complete response or appearance of one or more new lesions, until the first documented date of recurrent or progressive disease, whichever came first, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with complete response (CR).	Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Up to 5 years
Proportion of participants with partial response (PR).	Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Up to 5 years
Proportion of participants with stable disease (SD).	Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Up to 5 years
Proportion of participants with Grade 3 or higher adverse event.	Defined per Common Terminology Criteria for Adverse Events (CTCAE) v4.03	Up to 5 years
Number of patients with adverse events	Determine safety and tolerability of the intervention, defined per Common Terminology Criteria for Adverse Events (CTCAE) v4.03.	Up to 5 years
Number of participants with a worsening Patient Reported Outcomes of Adverse Events (PRO-AE) score	PRO-AE score defined per Patient Reported Outcome Measurement Information System (PROMIS) and Breast Cancer Prevention Trial (BCPT) Symptom Checklist.	At baseline and Day 1 of each cycle, up to 5 years (each cyle is 21 days)
Peak observed plasma concentration	Defined per maximum observed concentration (Cmax) and time of Cmax (Tmax).	Cycle 1, Day 1: 0 ,2,4 and 8 hours post treatment; Cycle 1, Day 15: 0 hours post treatment (each cyle is 21 days)

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: Pfizer
• Investigators: Principal Investigator: Lauren Nye, MD, KUCC

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2018
• Primary Completion (Actual): March 12, 2020
• Study Completion (Actual): February 3, 2021

Study Registration Dates

• First Submitted: October 9, 2018
• First Submitted That Met QC Criteria: October 15, 2018
• First Posted (Actual): October 17, 2018

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: palbociclib
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Immunoconjugates; Immunotoxins; Trastuzumab; Letrozole; Palbociclib; Ado-Trastuzumab Emtansine
• Other Study ID Numbers: 2017-IIT-HER2-Aspire

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes