Postmenopausal women presenting with HR-positive/HER2-negative metastatic breast cancer who have received at least 5 years of endocrine therapy in the adjuvant setting as treatment for early disease and remained disease free for more than 12 months following its completion or havede novo metastatic disease. MedDRA version: 18.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Palbociclib
Product Code: PD-0332991
Pharmaceutical Form: Capsule
INN or Proposed INN: PALBOCICLIB
Current Sponsor code: PD-0332991
Other descriptive name: Palbociclib
Concentration unit
Sponsors
GEICAM (Spanish Breast Cancer Research Group Foundation)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The patient has signed and dated the informed consent document and it has been obtained before conducting any procedure specifically for the study. 2. Availability of a tumor tissue sample, archival (primary tumour) or from the metastatic lesions (preferable) for the central ER, PgR and HER2 testing. 3.Histological/cytological confirmation of breast cancer with evidence of metastatic disease (loco-regional or distant), not amenable to resection or radiation therapy with curative intent. 4. Documented positive hormone receptor status (>1% of tumour cells with oestrogen receptor [ER] and/or progesterone receptor [PgR] expression) based on central testing on the most recent tumour biopsy. 5. Documented HER2-negative tumour based on central testing on the most recent tumour biopsy. HER2-negative tumour is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (FISH/CISH/SISH) defined as a HER2/CEP17 ratio 60 years. - Age equal to or 12 weeks. 12. Adequate organ and bone marrow function: ANC equal to or > 1,500/mm3 (1.5x109/L); - Platelets equal to or >100,000/mm3 (100x109/L); - Haemoglobin (Hgb) equal to or > 9g/dL (90g/L); - Serum creatinine equal or 60ml/min as calculated using the method standard for the institution; - Total serum bilirubin equal or =65 years) yes F.1.3.1 Number of subjects for this age range 190
Exclusion criteria
Exclusion criteria: 1.Prior systemic therapy for metastatic disease. Note: patients with a local recurrent disease treated with surgery (R0) and receiving a ?second hormonal adjuvant therapy for five years? will be allowed, provided they have remained disease free for more than 12 months following its completion. 2. Have ?de novo? locally advanced disease. 3. Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be potent CYP3A4 inducers, and drugs that are known to prolong the QT interval. 4. Presence of life-threatening metastatic visceral disease, defined as extensive hepatic involvement, or any degree of brain or leptomeningeal involvement (past or present), or symptomatic pulmonary lymphangitis spread, or any known bone marrow infiltration due to breast cancer. Patients with discrete pulmonary parenchymal metastases are eligible, provided their respiratory function is not significantly compromised as a result of disease. 5. Treatment with a non-approved or experimental drug within 4 weeks before randomization. 6. Prior treatment with any CDK4/6 inhibitor or fulvestrant. 7. Current or prior malignancy within previous 5 years (other than breast cancer or adequately treated basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix). 8. History of: ? Bleeding diathesis (i.e., disseminated intravascular coagulation [DIC], clotting factor deficiency) or long-term anticoagulant therapy (other than antiplatelet therapy and low dose warfarin). ? Hypersensitivity to active or inactive excipients of fulvestrant, palbociclib/placebo or castor oil. ? Any severe concomitant condition which makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the trial protocol, e.g. uncontrolled cardiac disease or uncontrolled diabetes mellitus. 9. QTc interval > 480msec, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes. 10. Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (eg, hypocalcaemia, hypokalaemia, hypomagnesaemia). 11. Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of palbociclib, such as history of GI surgery which may result in intestinal blind loops and patients with clinically significant gastro-paresis, short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease or diarrhoea of CTCAE grade > 1. 12. Prior hematopoietic stem cell or bone marrow transplantation. 13. Known human immunodeficiency virus infection. 14. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of fulvestrant in combination with palbociclib versus fulvestrant plus placebo in terms of the rate of Progression-Free Survival (PFS) at 1 year in postmenopausal women with HR-positive/HER2-negative metastatic breast cancer previously treated with endocrine therapy for at least 5 years and remaining disease free for more than 12 months following its completion or have de novo metastatic disease;Secondary Objective: To compare other efficacy measures between the treatment arms. To compare safety and tolerability between the treatment arms. To compare health related quality of life between the treatment arms.;Primary end point(s): - Rate of patients free of progression at 1 year assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by the investigator.;Timepoint(s) of evaluation of this end point: The primary analysis of rate of patients free of progression at 1 year will be carried out when all patients have been randomised and have had a follow-up of at least 12 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - The following efficacy endpoints will be measured: - Progression-Free Survival (PFS) assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by the investigator. - Objective Response Rate (ORR): Complete Response (CR) plus Partial Response (PR) according to RECIST version 1.1. - Clinical Benefit Rate (CBR): CR plus PR plus stable disease (SD) lasting = or > 24 weeks (+/-2 weeks) according to RECIST version 1.1. - Overall Survival (OS). - 1 year and 2 year survival probabilities. -Safety will be assessed by standard clinical and laboratory tests (hematology, serum chemistry). AEs grade will be defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 4.0. -Changes (mean score) and time to deterioration on EORTC QLQ-C30 Global Health Status/QoL and Physical Function and EORTC QLQ-BR23 Breast Module from baseline;Timepoint(s) of evaluation of this end point: FS will be analysed when at least 60% of patients have progressed (approximately 114 progression events) A descriptive summary of OS data will be carried out at the time of the PFS analysis when at least 60% of PFS events have occurred. A formal analysis of OS will subsequently be performed when at least 60% of patients (approximately 114 patients) have died. ORR and CBR will be analysed at the time-point of the primary analysis. | — |
Countries
Spain
Contacts
Public ContactClinical Operations Department
GEICAM (Spanish Breast Cancer Research Group Foundation)
Outcome results
None listed