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

NCT03709082 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 2017-IIT-HER2-Aspire
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 5

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.

Conditions

HER2-positive Breast Cancer; Breast Cancer Metastatic

Keywords

palbociclib

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Proportion of participants with complete response (CR).

  Up to 5 years

• Proportion of participants with partial response (PR).

  Up to 5 years

• Proportion of participants with stable disease (SD).

  Up to 5 years

• Proportion of participants with Grade 3 or higher adverse event.

  Up to 5 years

• Number of patients with adverse events

  Up to 5 years

Study Arms (4)

Phase 1: Palbociclib 75 mg

EXPERIMENTAL

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; Drug: Letrozole 2.5mg; Drug: T-DM1

Phase 1: Palbociclib 100 mg

EXPERIMENTAL

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; Drug: T-DM1; Drug: Palbociclib 100mg

Phase 1: Palbociclib 125 mg

EXPERIMENTAL

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; Drug: T-DM1; Drug: Palbociclib 125mg

Phase 2: RP2D

EXPERIMENTAL

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; Drug: T-DM1; Drug: Palbociclib

Interventions

Palbociclib 75mg DRUG

Oral Administration

Also known as: Ibrance

Phase 1: Palbociclib 75 mg

Letrozole 2.5mg DRUG

Oral Adminstration

Also known as: Femara

Phase 1: Palbociclib 100 mg; Phase 1: Palbociclib 125 mg; Phase 1: Palbociclib 75 mg; Phase 2: RP2D

T-DM1 DRUG

Intravenous Administration

Also known as: Ado-trastuzumab Emtansine, Kadcyla

Phase 1: Palbociclib 100 mg; Phase 1: Palbociclib 125 mg; Phase 1: Palbociclib 75 mg; Phase 2: RP2D

Palbociclib 100mg DRUG

Oral Administration

Also known as: Ibrance

Phase 1: Palbociclib 100 mg

Palbociclib 125mg DRUG

Oral Administration

Also known as: Ibrance

Phase 1: Palbociclib 125 mg

Palbociclib DRUG

Oral Administration

Also known as: Ibrance

Phase 2: RP2D

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Kansas Medical Center: lead
• Pfizer: collaborator

Study Sites (5)

The University of Kansas Cancer Center, West Clinic

Kansas City, Kansas, 66112, United States

Location

The University of Kansas Cancer Center, Westwood Campus

Kansas City, Kansas, 66205, United States

Location

The University of Kansas Cancer Center, Overland Park Clinic

Overland Park, Kansas, 66210, United States

Location

The University of Kansas Cancer Center, North Clinic

Kansas City, Missouri, 64154, United States

Location

The University of Kansas Cancer Center, Lee's Summit Clinic

Lee's Summit, Missouri, 64064, United States

Location

MeSH Terms

Interventions

palbociclib; Letrozole; Ado-Trastuzumab Emtansine

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Maytansine; Macrolides; Lactones; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lauren Nye, MD

  KUCC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 9, 2018
• First Posted: October 17, 2018
• Study Start: October 15, 2018
• Primary Completion: March 12, 2020
• Study Completion: February 3, 2021
• Last Updated: March 5, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)