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

Phase 3
Recruiting
Conditions
Breast Cancer Stage IV
Interventions
Drug: comparing both arms as regard the objective response rate, toxicity profile, quality of life, progression free survival
Registration Number
NCT05670054
Lead Sponsor
Mansoura University
Brief Summary

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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
116
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
palbociclib + fulvestrantcomparing both arms as regard the objective response rate, toxicity profile, quality of life, progression free survivalArm 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
Ribociclib + fulvestrantcomparing both arms as regard the objective response rate, toxicity profile, quality of life, progression free survivalArm 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
Primary Outcome Measures
NameTimeMethod
The rate of objective response and clinical benefitthe last patient recruited in the study will be followed up for at least 6 months

compare objective response rate and clinical benefit rate between the 2 arms

Incidence and grade of toxicitythe last patient recruited in the study will be followed up for at least 6 months

compare the incidence and grade of toxicity between the 2 arms

Compare Quality of life score of the patients using EORTC core quality of life questionaire version C-30each 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

compare the level of deterioration of the quality of life score between the 2 arms

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Oncology center mansoura university

🇪🇬

Mansoura, Dakahlia, Egypt

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