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

NCT03709082

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Palbociclib in Estrogen Receptor Positive (ER+) Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Metastatic Breast Cancer
  • 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 IDs

  • ORG STUDY ID: 2017-IIT-HER2-Aspire
  • NCT ID: NCT03709082

Conditions

  • HER2-positive Breast Cancer
  • Breast Cancer Metastatic

Interventions

DrugSynonymsArms
Palbociclib 75mgIbrancePhase 1: Palbociclib 75 mg
Letrozole 2.5mgFemaraPhase 1: Palbociclib 75 mg
T-DM1Ado-trastuzumab Emtansine, KadcylaPhase 1: Palbociclib 75 mg
Palbociclib 100mgIbrancePhase 1: Palbociclib 100 mg
Palbociclib 125mgIbrancePhase 1: Palbociclib 125 mg
PalbociclibIbrancePhase 2: RP2D

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase 1: Palbociclib 75 mgExperimentalPalbociclib 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
  • Palbociclib 75mg
  • Letrozole 2.5mg
  • T-DM1
Phase 1: Palbociclib 100 mgExperimentalPalbociclib 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
  • Letrozole 2.5mg
  • T-DM1
  • Palbociclib 100mg
Phase 1: Palbociclib 125 mgExperimentalPalbociclib 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
  • Letrozole 2.5mg
  • T-DM1
  • Palbociclib 125mg
Phase 2: RP2DExperimentalRecommended 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
  • Letrozole 2.5mg
  • T-DM1
  • Palbociclib

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Determine overall response rate (ORR), defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Secondary Outcome Measures

Measure:Proportion of participants with complete response (CR).
Time Frame:Up to 5 years
Safety Issue:
Description:Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measure:Proportion of participants with partial response (PR).
Time Frame:Up to 5 years
Safety Issue:
Description:Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measure:Proportion of participants with stable disease (SD).
Time Frame:Up to 5 years
Safety Issue:
Description:Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measure:Proportion of participants with Grade 3 or higher adverse event.
Time Frame:Up to 5 years
Safety Issue:
Description:Defined per Common Terminology Criteria for Adverse Events (CTCAE) v4.03
Measure:Number of patients with adverse events
Time Frame:Up to 5 years
Safety Issue:
Description:Determine safety and tolerability of the intervention, defined per Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
Measure: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)
Safety Issue:
Description:PRO-AE score defined per Patient Reported Outcome Measurement Information System (PROMIS) and Breast Cancer Prevention Trial (BCPT) Symptom Checklist.
Measure: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)
Safety Issue:
Description:Defined per maximum observed concentration (Cmax) and time of Cmax (Tmax).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Kansas Medical Center

Trial Keywords

  • palbociclib

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