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.
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
Drug | Synonyms | Arms |
---|
Palbociclib 75mg | Ibrance | Phase 1: Palbociclib 75 mg |
Letrozole 2.5mg | Femara | Phase 1: Palbociclib 100 mg |
T-DM1 | Ado-trastuzumab Emtansine, Kadcyla | Phase 1: Palbociclib 100 mg |
Palbociclib 100mg | Ibrance | Phase 1: Palbociclib 100 mg |
Palbociclib 125mg | Ibrance | Phase 1: Palbociclib 125 mg |
Palbociclib | Ibrance | Phase 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
Name | Type | Description | Interventions |
---|
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 | - Palbociclib 75mg
- Letrozole 2.5mg
- 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 | - Letrozole 2.5mg
- T-DM1
- 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 | - Letrozole 2.5mg
- T-DM1
- 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 | - 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: | Active, not recruiting |
Lead Sponsor: | University of Kansas Medical Center |
Trial Keywords
Last Updated
November 25, 2020