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

Phase 2

Completed

• Conditions: Metastatic Breast Cancer
• Interventions: Drug: Palbociclib; Drug: Letrozole; Drug: Fulvestrant

• Registration Number: NCT02491983
• Lead Sponsor: MedSIR

Brief Summary

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

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).

Study Timeline

• Study First Submitted: 2015-06-29
• Study First Submitted QC: 2015-07-03
• Study First Posted: 2015-07-08
• Study Start: 2015-08
• Primary Completion: 2020-01
• Study Completion: 2020-01
• Results First Submitted: 2023-03-28
• Status Verified: 2024-10
• Results First Submitted QC: 2024-10-22
• Last Update Submitted: 2024-10-22
• Results First Posted: 2024-12-09
• Last Update Posted: 2024-12-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 486

Inclusion Criteria

1. Women 18 years or older with metastatic or locally advanced disease, not amenable to curative therapy
2. Confirmed diagnosis of HR+/HER2- breast cancer
3. Post-menopausal status
4. No prior chemotherapy line in the metastatic setting
5. Measurable disease defined by RECIST version 1.1, or non-measurable disease
6. Eastern Cooperative Oncology Group (ECOG) PS 0-1
7. Adequate organ and marrow function, resolution of all toxic effects of prior therapy or surgical procedures
8. 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

1. ER or HER2 unknown disease
2. HER2 positive disease based on local laboratory results
3. Locally advanced breast cancer candidate for a radical treatment
4. Prior (neo)adjuvant endocrine treatment with DFI ≤ 12-months from completion of treatment.
5. Patients with rapidly progressive visceral disease or visceral crisis.
6. Major surgery within 4 weeks of start of study drug
7. Patients with an active, bleeding diathesis
8. Serious concomitant systemic disorder incompatible with the study
9. Are unable to swallow tablets
10. Chronic daily treatment with corticosteroids with a dose of ≥ 10mg/day methylprednisolone equivalent
11. Known active uncontrolled or symptomatic CNS metastases
12. Known hypersensitivity to letrozole, fulvestrant or any of their excipients, or to any PD-0332991 excipients
13. 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
14. Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Palbociclib	Combination of Palbociclib and Letrozole
Arm B	Palbociclib	Combination of Palbociclib and Fulvestrant
Arm A	Letrozole	Combination of Palbociclib and Letrozole
Arm B	Fulvestrant	Combination of Palbociclib and Fulvestrant

Primary Outcome Measures

Name	Time	Method
1-year Progression Free Survival	One year	Percentage of patients who are alive and without evidence of tumor progression (defined using RECIST v1.1)

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Grade 3/4 Adverse Events, SAEs, Deaths and Discontinuations •	Through study completion. From baseline up to 51 months.	Grade 3/4 adverse events, SAEs, deaths and discontinuations following the CTCAE v5 criteria
Time To Progression (TTP)	Through study completion. From baseline up to 51 months.	Time from randomization to disease progression
Overall Survival (OS)	Through study completion. From baseline up to 51 months.	Time from date of randomization to date of death due to any cause
Clinical Benefit Rate	Through study completion. From baseline up to 51 months.	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.
Overall Response Rate	Through study completion. From baseline up to 51 months.	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)

Trial Locations

Locations (2)

MedSIR investigative site B; 🇪🇸 Zaragoza, Spain

MedSIR investigative site; 🇬🇧 Truro, United Kingdom