Palbociclib in Estrogen Receptor Positive (ER+) Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Metastatic Breast Cancer
- Conditions
- HER2-positive Breast CancerBreast Cancer Metastatic
- Interventions
- Registration Number
- NCT03709082
- Lead Sponsor
- University of Kansas Medical Center
- 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 available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Female
- Target Recruitment
- 3
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1: Palbociclib 125 mg Letrozole 2.5mg 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 Phase 1: Palbociclib 75 mg T-DM1 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 Phase 1: Palbociclib 75 mg Letrozole 2.5mg 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 Phase 1: Palbociclib 125 mg T-DM1 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 Phase 1: Palbociclib 125 mg Palbociclib 125mg 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 Phase 1: Palbociclib 75 mg Palbociclib 75mg 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 Phase 1: Palbociclib 100 mg Letrozole 2.5mg 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 Phase 1: Palbociclib 100 mg Palbociclib 100mg 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 Phase 2: RP2D Letrozole 2.5mg 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 Phase 2: RP2D Palbociclib 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 Phase 1: Palbociclib 100 mg T-DM1 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 Phase 2: RP2D T-DM1 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
- Primary Outcome Measures
Name Time Method Rate of Overall Response 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
Name Time Method Peak observed plasma concentration 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).
Proportion of participants with stable disease (SD). 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. Up to 5 years Defined per Common Terminology Criteria for Adverse Events (CTCAE) v4.03
Number of patients with adverse events Up to 5 years Determine safety and tolerability of the intervention, defined per Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
Proportion of participants with complete response (CR). Up to 5 years Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Proportion of participants with partial response (PR). Up to 5 years Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Number of participants with a worsening Patient Reported Outcomes of Adverse Events (PRO-AE) score 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.
Trial Locations
- Locations (5)
The University of Kansas Cancer Center, Overland Park Clinic
🇺🇸Overland Park, Kansas, United States
The University of Kansas Cancer Center, Westwood Campus
🇺🇸Kansas City, Kansas, United States
The University of Kansas Cancer Center, West Clinic
🇺🇸Kansas City, Kansas, United States
The University of Kansas Cancer Center, Lee's Summit Clinic
🇺🇸Lee's Summit, Missouri, United States
The University of Kansas Cancer Center, North Clinic
🇺🇸Kansas City, Missouri, United States