Cyclin Dependant Kinase 4/6 (CDK4/6) Inhibitors as a Second Line Treatment in Metastatic Breast Cancer Patients

Breast cancer is the commonest malignancy among females and one of the leading causes of death worldwide. Many drugs have been developed over the years to try to extend survival among these patients including cyclin dependant kinase inhibitors. Cyclin dependant kinase inhibitors (CDK inhibitors) mainly Palbociclib (PAL), ribociclib (RIB) and abemaciclib (ABM) are approved for treatment of hormone receptor positive, HER2 negative advanced breast cancer in the 1st line and subsequent lines in combination with aromatase inhibitors or fulvestrant. Studies showed that they extend progression free survival and recently they showed overall survival benefit. In this study investigators compare Palbociclib+ fulvestrant VS Ribociclib + fulvestrant as a second line treatment in metastatic ER+ve her2 -ve BC in oncology center mansoura university egyptian patients.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer Stage IV
• Intervention / Treatment: Drug: comparing both arms as regard the objective response rate, toxicity profile, quality of life, progression free survival

Detailed Description

Breast cancer is the commonest malignancy among females and one of the leading causes of death worldwide. Many drugs have been developed over the years to try to extend survival among these patients including cyclin dependant kinase inhibitors. Cyclin dependant kinase inhibitors (CDK inhibitors) mainly Palbociclib (PAL), ribociclib (RIB) and abemaciclib (ABM) are approved for treatment of hormone receptor positive, HER2 negative advanced breast cancer in the 1st line and subsequent lines in combination with aromatase inhibitors or fulvestrant. Studies showed that they extend progression free survival and recently they showed overall survival benefit. In this study investigators compare Palbociclib+ fulvestrant VS Ribociclib + fulvestrant as a second line treatment in metastatic ER+ve her2 -ve BC in oncology center mansoura university egyptian patients. The efficacy and comparative toxicity of CDK inhibitors were indirectly compared in a number of trials. Despite differences in inclusion criteria and follow-up length, second-line trials showed similar characteristics.

Unfortunately, despite the similar efficacy and overall response rate (ORR) and a slightly different but near-identical spectrum of adverse events, both agents have not been directly compared with each other. This study aims to fill that gap, and evaluate the toxicity, tolerability and response rate of ribociclib plus fulvestrant versus palbociclib plus fulvestrant, to inform the decision makers.

• Study Type: Interventional
• Enrollment (Anticipated): 116
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: manar hamed, MD; Phone Number: +201063678209; Email: manarhamed@mans.edu.eg
• Study Contact Backup: Name: ahmed tantawy, MD; Phone Number: 01091203484; Email: hamedmanar9@gmail.com

Study Locations

• Egypt
  • Dakahlia
    • Mansoura, Dakahlia, Egypt, 35516
      • Recruiting
      • Oncology center Mansoura University
      • Contact: ahmed tantawy, MD; Phone Number: 01091203484; Email: hamedmanar9@gmail.com
      • Contact: manar hamed, MD; Phone Number: 01063678209; Email: manarhamed@mans.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• - Pathologically proven diagnosis of adenocarcinoma of the breast with evidence of metastatic disease either progression on adjuvant hormonal or progression on 1st line hormonal for metastatic disease.
• Documentation of ER-positive and/or PR-positive and HER2 negative.
• Prior use of endocrine therapy.
• age >18 years old.
• ECOG: 0-2
• Postmenopausal is defined as: age>60 years old or < 60 years old with cessation off menstruation for at least 12 months and FSH or E2 in postmenopausal range or patients who underwent bilateral oophorectomy.
• Premenopausal is defined if not meeting the criteria of postmenopausal. They are obligated to receive LHRH agonist with their treatment.

Exclusion Criteria:

• - Age < 18 years old
• Patients with advanced/metastatic, symptomatic, visceral spread(visceral crisis) , that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement).
• 2nd malignancy other than breast cancer
• ECOG more than 3

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: palbociclib + fulvestrant; Arm A includes patients who receive palbociclib 125 mg tab/day for 3 weeks and 1 week rest+ Fulvestrant 500 mg IM injection d1, d15, d29 1st cycle then every month	Drug: comparing both arms as regard the objective response rate, toxicity profile, quality of life, progression free survival; comparing both arms as regard the objective response rate, toxicity profile, quality of life, progression free survival
Active Comparator: Ribociclib + fulvestrant; Arm B includes patients who receive ribociclib 200 mg 3 tabs/day for 3 weeks and 1 week rest+ Fulvestrant 500 mg IM injection d1, d15, d29 1st cycle then every month	Drug: comparing both arms as regard the objective response rate, toxicity profile, quality of life, progression free survival; comparing both arms as regard the objective response rate, toxicity profile, quality of life, progression free survival

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of objective response and clinical benefit	compare objective response rate and clinical benefit rate between the 2 arms	the last patient recruited in the study will be followed up for at least 6 months
Incidence and grade of toxicity	compare the incidence and grade of toxicity between the 2 arms	the last patient recruited in the study will be followed up for at least 6 months
Compare Quality of life score of the patients using EORTC core quality of life questionaire version C-30	compare the level of deterioration of the quality of life score between the 2 arms	each patient will answer the QOL score at D0, 3rd and 6 months of treatment as long as he is hasn't progressed on treatment during the 1st 6 months

Collaborators and Investigators

• Sponsor: Mansoura University
• Investigators: Principal Investigator: manar hamed, MD, Oncology center Mansoura University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Anticipated): October 15, 2023
• Study Completion (Anticipated): December 15, 2023

Study Registration Dates

• First Submitted: December 17, 2022
• First Submitted That Met QC Criteria: January 1, 2023
• First Posted (Actual): January 4, 2023

Study Record Updates

• Last Update Posted (Actual): January 4, 2023
• Last Update Submitted That Met QC Criteria: January 1, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: MD.22.07.674

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: the results of the study will be shared and published
• IPD Sharing Time Frame: at january 2023 for 3 years
• IPD Sharing Access Criteria: All data will be available to the fellow researchers
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No