Palbociclib in Combination With Fulvestrant or Letrozole in Patients With ER+, HER2- Advanced Breast Cancer

Study Overview
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Brief Summary
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This is an international, randomized, open-label, controlled, multicenter phase II clinical trial to investigate and compare the safety and efficacy of palbociclib combined with fulvestrant or letrozole in women with ER+, HER2- locally advanced or metastatic breast cancer.

Detailed Description
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Patients will be stratified by site of disease (visceral vs. non-visceral) and by onset of metastatic disease diagnose (patients metastatic de novo versus non de novo).

Official Title
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A Randomized, Multicenter, Open-label, Phase II Trial to Evaluate the Efficacy and Safety of Palbociclib in Combination With Fulvestrant or Letrozole in Patients With HER2 Negative, ER+ Metastatic Breast Cancer

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Palbociclib
* Drug: Fulvestrant
* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women 18 years or older with metastatic or locally advanced disease, not amenable to curative therapy Confirmed diagnosis of HR+/HER2- breast cancer Post-menopausal status No prior chemotherapy line in the metastatic setting Measurable disease defined by RECIST version 1.1, or non-measurable disease Eastern Cooperative Oncology Group (ECOG) PS 0-1 Adequate organ and marrow function, resolution of all toxic effects of prior therapy or surgical procedures Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCICTCAE version 4.0 Grade equal or minor than 1 Exclusion Criteria: ER or HER2 unknown disease HER2 positive disease based on local laboratory results Locally advanced breast cancer candidate for a radical treatment Prior (neo)adjuvant endocrine treatment with DFI ≤ 12-months from completion of treatment. Patients with rapidly progressive visceral disease or visceral crisis. Major surgery within 4 weeks of start of study drug Patients with an active, bleeding diathesis Serious concomitant systemic disorder incompatible with the study Are unable to swallow tablets Chronic daily treatment with corticosteroids with a dose of ≥ 10mg/day methylprednisolone equivalent Known active uncontrolled or symptomatic CNS metastases Known hypersensitivity to letrozole, fulvestrant or any of their excipients, or to any PD-0332991 excipients QTc > 480 msec on basal assessments, personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Combination of Palbociclib and Letrozole | Drug: Palbociclib<br> <br> * Other names: PD-0332991;Drug: Letrozole<br> <br> * Other names: Femara;|
| Experimental: Arm B<br>Combination of Palbociclib and Fulvestrant | Drug: Palbociclib<br> <br> * Other names: PD-0332991;Drug: Fulvestrant<br> <br> * Other names: Faslodex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year Progression Free Survival | Percentage of patients who are alive and without evidence of tumor progression at 52 weeks of study entry. | Baseline up to 52 weeks after last patient entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 3/4 adverse events, SAEs, deaths and discontinuations • | CTCAE v5 | Baseline up to 52 weeks after last patient entry | 
| Time To Progression (TTP) | Time from randomization to disease progression | Baseline up to 52 weeks after last patient entry | 
| Overall Survival (OS) | Time from date of randomization to date of death due to any cause | Baseline up to 52 weeks after last patient entry | 
| Clinical Benefit Rate | Percentage of patients who experience a CR, PR or stable disease (for at least 24 weeks) and assessed by modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria. | Baseline up to 52 weeks after last patient entry | 
| Overall Response Rate | proportion of patients with best overall response of confirmed complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST criteria guidelines (version 1.1) | Baseline up to 52 weeks after last patient entry | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic breast cancer, Endocrine receptors positive, HER-2 negative