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

HER2-positive Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03709082
• Other study ID #: 2017-IIT-HER2-Aspire
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: October 15, 2018
• Est. completion date: February 3, 2021

Study information

• Verified date: March 2024
• Source: University of Kansas Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: February 3, 2021
• Est. primary completion date: March 12, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer Metastatic
• Breast Neoplasms
• HER2-positive Breast Cancer

Intervention

Drug:
• Palbociclib 75mg
Oral Administration
• Letrozole 2.5mg
Oral Adminstration
• T-DM1
Intravenous Administration
• Palbociclib 100mg
Oral Administration
• Palbociclib 125mg
Oral Administration
• Palbociclib
Oral Administration

Locations

Country	Name	City	State
United States	The University of Kansas Cancer Center, North Clinic	Kansas City	Missouri
United States	The University of Kansas Cancer Center, West Clinic	Kansas City	Kansas
United States	The University of Kansas Cancer Center, Westwood Campus	Kansas City	Kansas
United States	The University of Kansas Cancer Center, Lee's Summit Clinic	Lee's Summit	Missouri
United States	The University of Kansas Cancer Center, Overland Park Clinic	Overland Park	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
University of Kansas Medical Center	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Proportion of participants with complete response (CR).	Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Up to 5 years
Secondary	Proportion of participants with partial response (PR).	Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Up to 5 years
Secondary	Proportion of participants with stable disease (SD).	Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Up to 5 years
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)