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Trial record 1 of 1 for:    NCT03709082
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Palbociclib in Estrogen Receptor Positive (ER+) Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT03709082
Recruitment Status : Recruiting
First Posted : October 17, 2018
Last Update Posted : November 13, 2019
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
University of Kansas Medical Center

Tracking Information
First Submitted Date  ICMJE October 9, 2018
First Posted Date  ICMJE October 17, 2018
Last Update Posted Date November 13, 2019
Actual Study Start Date  ICMJE October 15, 2018
Estimated Primary Completion Date October 15, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 15, 2018)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 15, 2018)
  • 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
  • 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
  • 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
  • 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
  • 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.
  • 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.
  • 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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Palbociclib in Estrogen Receptor Positive (ER+) Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Metastatic Breast Cancer
Official Title  ICMJE A Phase I/II Study of Palbociclib, Letrozole and T-DM1 in Trastuzumab Refractory Estrogen Receptor Positive (ER+) and HER2 Positive Metastatic Breast Cancer
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • HER2-positive Breast Cancer
  • Breast Cancer Metastatic
Intervention  ICMJE
  • 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
  • Drug: Palbociclib 100mg
    Oral Administration
    Other Name: Ibrance
  • Drug: Palbociclib 125mg
    Oral Administration
    Other Name: Ibrance
  • Drug: Palbociclib
    Oral Administration
    Other Name: Ibrance
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: Palbociclib 75mg
    • Drug: Letrozole 2.5mg
    • Drug: T-DM1
  • 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
    Interventions:
    • Drug: Letrozole 2.5mg
    • Drug: T-DM1
    • Drug: Palbociclib 100mg
  • 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
    Interventions:
    • Drug: Letrozole 2.5mg
    • Drug: T-DM1
    • Drug: Palbociclib 125mg
  • 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
    Interventions:
    • Drug: Letrozole 2.5mg
    • Drug: T-DM1
    • Drug: Palbociclib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 8, 2019)
4
Original Estimated Enrollment  ICMJE
 (submitted: October 15, 2018)
62
Estimated Study Completion Date  ICMJE October 15, 2025
Estimated Primary Completion Date October 15, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kerry Hepler 913-945-7552 ctnursenav@kumc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03709082
Other Study ID Numbers  ICMJE 2017-IIT-HER2-Aspire
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Kansas Medical Center
Study Sponsor  ICMJE University of Kansas Medical Center
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: Lauren Nye, MD KUCC
PRS Account University of Kansas Medical Center
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP