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

Sponsor

University of Kansas Medical Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03709082

Collaborator

Pfizer (Industry)

Enrollment

Locations

Arms

Anticipated Duration (Months)

0.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
HER2-positive Breast Cancer Breast Cancer Metastatic	Drug: Palbociclib 75mg Drug: Letrozole 2.5mg Drug: T-DM1 Drug: Palbociclib 100mg Drug: Palbociclib 125mg Drug: Palbociclib	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

3 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 15, 2018

Actual Primary Completion Date :

Mar 12, 2020

Anticipated Study Completion Date :

Oct 15, 2025

Arms and Interventions

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: 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

Outcome Measures

Primary Outcome Measures

Rate of Overall Response [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]
Determine overall response rate (ORR), defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Kansas Cancer Center, West Clinic	Kansas City	Kansas	United States	66112
2	The University of Kansas Cancer Center, Westwood Campus	Kansas City	Kansas	United States	66205
3	The University of Kansas Cancer Center, Overland Park Clinic	Overland Park	Kansas	United States	66210
4	The University of Kansas Cancer Center, North Clinic	Kansas City	Missouri	United States	64154
5	The University of Kansas Cancer Center, Lee's Summit Clinic	Lee's Summit	Missouri	United States	64064