Clinical trial NCT03709082: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: HER2-positive Breast Cancer
Breast Cancer Metastatic
Keywords: palbociclib
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2018-10-17
Enrollment: 3
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Rate of Overall Response
timeFrame: 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
Secondary outcomes:
measure: Proportion of participants with complete response (CR).
timeFrame: Up to 5 years
measure: Proportion of participants with partial response (PR).
timeFrame: Up to 5 years
measure: Proportion of participants with stable disease (SD).
timeFrame: Up to 5 years
measure: Proportion of participants with Grade 3 or higher adverse event.
timeFrame: Up to 5 years
measure: Number of patients with adverse events
timeFrame: Up to 5 years
measure: Number of participants with a worsening Patient Reported Outcomes of Adverse Events (PRO-AE) score
timeFrame: At baseline and Day 1 of each cycle, up to 5 years (each cyle is 21 days)
measure: Peak observed plasma concentration
timeFrame: 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)
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: The University of Kansas Cancer Center, West Clinic
state: Kansas
city: Kansas City
country: United States
facility: The University of Kansas Cancer Center, Westwood Campus
state: Kansas
city: Overland Park
country: United States
facility: The University of Kansas Cancer Center, Overland Park Clinic
state: Kansas
city: Kansas City
country: United States
facility: The University of Kansas Cancer Center, North Clinic
state: Missouri
city: Lee's Summit
country: United States
facility: The University of Kansas Cancer Center, Lee's Summit Clinic
state: Missouri
Study officials:
affiliation: KUCC
name: Lauren Nye, MD
role: PRINCIPAL_INVESTIGATOR
References: