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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03709082
Recruitment Status : Active, not recruiting
First Posted : October 17, 2018
Last Update Posted : November 25, 2020
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
University of Kansas Medical Center

Study Description
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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
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Study Type : Interventional  (Clinical Trial)
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 : October 15, 2018
Actual Primary Completion Date : March 12, 2020
Estimated Study Completion Date : October 15, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Palbociclib

Arms and Interventions
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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 Name: Ibrance

Drug: Letrozole 2.5mg
Oral Adminstration
Other Name: 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 Name: Femara

Drug: T-DM1
Intravenous Administration
Other Names:
  • Ado-trastuzumab Emtansine
  • Kadcyla

Drug: Palbociclib 100mg
Oral Administration
Other Name: 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 Name: Femara

Drug: T-DM1
Intravenous Administration
Other Names:
  • Ado-trastuzumab Emtansine
  • Kadcyla

Drug: Palbociclib 125mg
Oral Administration
Other Name: 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 Name: Femara

Drug: T-DM1
Intravenous Administration
Other Names:
  • Ado-trastuzumab Emtansine
  • Kadcyla

Drug: Palbociclib
Oral Administration
Other Name: Ibrance


Outcome Measures
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Primary Outcome Measures :
  1. Rate of Overall Response [ Time Frame: 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 :
  1. Proportion of participants with complete response (CR). [ Time Frame: Up to 5 years ]
    Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  2. Proportion of participants with partial response (PR). [ Time Frame: Up to 5 years ]
    Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  3. Proportion of participants with stable disease (SD). [ Time Frame: Up to 5 years ]
    Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  4. Proportion of participants with Grade 3 or higher adverse event. [ Time Frame: Up to 5 years ]
    Defined per Common Terminology Criteria for Adverse Events (CTCAE) v4.03

  5. Number of patients with adverse events [ Time Frame: Up to 5 years ]
    Determine safety and tolerability of the intervention, defined per Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

  6. Number of participants with a worsening Patient Reported Outcomes of Adverse Events (PRO-AE) score [ Time Frame: 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.

  7. Peak observed plasma concentration [ Time Frame: 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
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03709082


Locations
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United States, Kansas
The University of Kansas Cancer Center, West Clinic
Kansas City, Kansas, United States, 66112
The University of Kansas Cancer Center, Westwood Campus
Kansas City, Kansas, United States, 66205
The University of Kansas Cancer Center, Overland Park Clinic
Overland Park, Kansas, United States, 66210
United States, Missouri
The University of Kansas Cancer Center, North Clinic
Kansas City, Missouri, United States, 64154
The University of Kansas Cancer Center, Lee's Summit Clinic
Lee's Summit, Missouri, United States, 64064
Sponsors and Collaborators
University of Kansas Medical Center
Pfizer
Investigators
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Principal Investigator: Lauren Nye, MD KUCC
More Information
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Responsible Party: University of Kansas Medical Center
ClinicalTrials.gov Identifier: NCT03709082    
Other Study ID Numbers: 2017-IIT-HER2-Aspire
First Posted: October 17, 2018    Key Record Dates
Last Update Posted: November 25, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by University of Kansas Medical Center:
palbociclib
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Ado-Trastuzumab Emtansine
Letrozole
Palbociclib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
 Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Protein Kinase Inhibitors
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Immunotoxins
Immunoconjugates
Immunologic Factors