Tumor Response Time of Palbociclib in Combination With AI in Real-world Chinese Patients

Study Overview
=================
Brief Summary
-----------------
The international treatment guidelines now include recommendations for the use of CDK 4/6 inhibitors in combination with hormone agents for the treatment of postmenopausal women with hormone-receptor-positive/HER2-negative ABC as the first-line standard therapy in endocrine sensitive patients. Nevertheless, it is generally thought that chemotherapy is associated with greater and earlier tumor response, especially in case of high burden of disease. In a retrospective analysis of real-world clinical practice (2002-2012) from US, only 60% of patients initiated ET as the first treatment following metastatic diagnosis . In the real-life world of China, a large number of HR+/HER2- ABC patients with non-visceral crisis also received chemotherapy in first-line treatment, even though the ORR is similar compared with CDK4/6 inhibitors with endocrine therapy. Zhejiang Cancer Hospital retrospective analysis of 5 cases of advanced breast cancer first-line use of Ibance + ET, they were evaluated within 50 days (from 27days to 50days). Based on the early response time observed in real-world data mentioned above, it is proposed a prospective study to further observe the tumor reduction rate in real-world, including to identify the time of patient symptom improvement according to the quality of life scale.

Detailed Description
-----------------
According to the early assessment(4 weeks) , this prospective study comprehensively investigate TTR of Palbociclib+ET in the first line treatment for HR+/HER2- MBC patients in China real-world study. Furthermore, evaluate the Early Tumor Shrinkage(ETS) of Palbociclib + ET, and assess Treatment Free Interval (TFI) with TTR and ETS；TFI was analyzed at the following time points: ≤24, >24, ≤36, > 36, ≤48, >48 months. Accroding to the follow-up of QoL questionnaire, understand the clinical symptoms improvements time. Meanwhile, cooperation with radiology department, establish a model for predicting early response by observing the imaging and clinical pathological characteristics of patients with ETS.

Official Title
-----------------
An Open-label, Prospective Study of Tumor Response Time of Palbociclib in Combination With AI in Real-world First-line Treatment of Postmenopausal Chinese Patients With ER (+) HER2 (-) Metastatic Breast Cancer

Conditions
-----------------
Breast Neoplasms

Intervention / Treatment
-----------------
* Drug: Palbociclib
* Drug: AI


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult women (≥ 18 years of age) with proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated. Documentation of histologically or cytologically confirmed diagnosis of estrogen-receptor positive (ER+, > 10%) breast cancer based on local laboratory results. Previously untreated with any systemic anti-cancer therapy for their locoregionally recurrent or metastatic ER+ disease. Postmenopausal women. At least one measurable lesion as defined per RECIST v.1.1. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2. Adequate organ and marrow function. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: Patients with advanced, symptomatic, visceral spread, that are at risk of life-threatening complications including any of the following: massive uncontrolled effusions [pleural, pericardial, peritoneal] pulmonary lymphangitis, over 50% liver involvement Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis,or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment. Prior treatment with any CDK4/6 inhibitor. QTc >480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP). Female patients who are pregnant or nursing.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Palbociclib-AI<br>ER(+)/HER2(-) patients with histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease receive palbociclib PO daily on days 1-21, combined with AI as first-line treatment Disease assessments measured by CT imaging will be performed at first 4 weeks, 8weeks, then every 8weeks (± 7 days) from the date of randomization until radiographic/clinical documentation of progressive disease per the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. | Drug: Palbociclib<br>* Palbociclib,125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment<br>* Other names: Ibrabce;Drug: AI<br>* AI, orally once daily (continuously)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early Tumor Shrinkage (ETS) | 10% change in the sum of the longest diameters (SLD) of target lesions at the first scan after 4weeks and 8weeks of treatment. | 4 weeks, 8weeks | 
| Time To Response (TTR) | Time to first documented complete of partial response. | Up to approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the overall complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1) | Up to approximately 24 months | 
| Number of participants with Adverse Events per CTCAE version 4.03 and type | Safety will be determined by type, severity of adverse events per CTCAE version 4.03 and type | Up to approximately 24 months | 
| Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30 | At least 10% relative to baseline worsening of the corresponding scale score (without further improvement above the threshold) or death due to any cause. | Up to approximately 24 months | 
| Overall Survival (OS) | time to death due to any cause | Randomization to death from any cause, through the end of study (approximately 60months)] |