Metastatic breast cancer
Conditions
Interventions
Product Name: Palbociclib
Product Code: PD-0332991
Pharmaceutical Form: Capsule
INN or Proposed INN: PALBOCICLIB
Current Sponsor code: P
Sponsors
Medica Scientia Innovation Research (MedSIR)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Postmenopausal women, as defined by any of the following criteria: - Age 60 or over - Age 45 to 59 years and meets ?1 of the following criteria: Amenorrhea for ?24 months Amenorrhea for 3.0 x 109/L, absolute neutrophil count (ANC) >1.0 x 109/L, platelet count >75.0 x109/L, and hemoglobin >10.0 g/dL (>6.2 mmol/L) - Hepatic: bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 104
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study if they meet ANY of the following criteria: 1. ER or HER2 unknown disease 2. HER2 positive disease based on local laboratory results (performed by immunohistochemistry/FISH) 3. Locally advanced breast cancer candidate for a radical treatment. 4. Prior endocrine therapy in the metastatic setting (If endocrine therapy has been administered in the (neo)adjuvant setting, disease-free survival should be greater than 12 months). 5. Patients with rapidly progressive visceral disease or visceral crisis. 6. Have had a major surgery (defined as requiring general anaesthesia) or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery or patients that may require major surgery during the course of the study. 7. Patients with an active, bleeding diathesis. 8. Have a serious concomitant systemic disorder (e.g. active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator), previous history of bleeding diathesis, or anti-coagulation treatment (The use of low molecular weight heparin is allowed as soon as it is used as prophylaxis intention). 9. Are unable to swallow tablets. 10. History of malabsorption syndrome or other condition that would interfere with enteral absorption. 11. Chronic daily treatment with corticosteroids with a dose of ? 10mg/day methylprednisolone equivalent (excluding inhaled steroids). 12. Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral oedema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy (e.g., radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4weeks before randomization 13. Known hypersensitivity to letrozole, fulvestrant or any of their excipients, or to any PD-0332991 excipients. 14. 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 (TdP). 15. Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of the combination of palbociclib plus fulvestrant or palbociclib plus letrozole in terms of 1-year progression-free survival (PFS) in patients with hormone-sensitive HER2-negative metastatic or locally advanced breast cancer; Secondary Objective: - To evaluate the safety and tolerability of the combination of palbociclib plus fulvestrant or letrozole. - To correlate the safety profile of palbociclib combined with fulvestrant or letrozole with baseline patient characteristics. - To compare the time to progression (TTP) of the combination of palbociclib plus fulvestrant with palbociclib plus letrozole. - To compare the overall survival (OS) of the combination of palbociclib plus fulvestrant with palbociclib plus letrozole. - To compare the clinical response (in terms of clinical benefit and overall response) of the combination of palbociclib plus fulvestrant with palbociclib plus letrozole. ;Primary end point(s): The primary endpoint for this study is 1-year PFS, which is defined as the time from randomization to death or disease progression, as assessed by the investigator per RECIST v1.1 at 52 weeks.;Timepoint(s) of evaluation of this end point: 52 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoint-Safety: Patient safety and adverse events will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4 [1]. Grade 3 and 4 adverse events and serious adverse events will be assessed to determine the safety and tolerability of the different drug combinations. Secondary Endpoints-Efficacy: The time to progression (TTP), overall survival (OS), overall response rate (ORR) and clinical benefit rate (CBR) will be determined to assess the efficacy of the drug combinations. TTP is defined as the time from randomization to disease progression, as assessed by the investigator per RECIST v1.1. OS is defined as the time from randomization until death from any cause. The ORR is defined as the 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). An objective response needs to be confirmed at least 4 weeks after the initial response. The CBR is defined as the 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. ;Timepoint(s) of evaluation of this end point: 36 months | — |
Countries
Czech Republic, Germany, Italy, Russian Federation, Saudi Arabia, Spain, United Arab Emirates, United Kingdom
Contacts
Public ContactClinical Operations
TFS Trial Form Support SAS
Outcome results
None listed