Early HR(+)/HER2(-) Breast Cancer MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: IBRANCE
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PALBOCICLIB
CAS Number: 571190-30-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
Sponsors
Medica Scientia Innovation Research (MEDSIR)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female patients over 18 years of age. 2. Patients have been informed about the nature of study, have agreed to participate in the study, and have signed the informed consent form prior to participation in any study-related activities. 3. Premenopausal and postmenopausal women. Premenopausal women must be treated with LHRH analogue since patient pre- registration. Premenopausal or postmeno-pausal status should have been established before starting study treatment with letrozole plus palbociclib based on the following classification: a) Postmenopausal status is defined as either: o Prior bilateral oophorectomy; Or o Age>60 years; Or o Age2,0 cm (T2-4 according to TNM staging system, but always >2,0 cm). 9. Limited node involvement (N0-2, according to TNM staging system), as assessed by a sentinel lymph node biopsy, an axillary dissection, or both, and as defined by the Sixth Edition of the American Joint Committee on Cancer (AJCC) staging criteria. 10. No metastatic disease (M0, according to TNM staging system). 11. Available pre-treatment tissue sample (biopsy) material (formalin- fixed paraffin-embedded (FFPE)) for RS central evaluation by the Assay. 12. Patients agree to collection of tissue biopsy from the primary breast cancer at the time of study inclusion (screening), at Cycle 1 Day 14 of treatment, and after 24 weeks, or if experience intolerable side effects, disease progression, or withdraw during 24 weeks of study treatment. 13. Patients must have biopsable and measurable disease (according to RECIST criteria v.1.1). 14. No prior chemotherapy, endocrine or radiation therapy for current disease. 15. Adequate organ function: a) Hematological: White blood cell (WBC) count = 3.0 x 109/L, absolute neutrophil count (ANC) = 1.5x 109/L, platelet count = 75.0 x109/L, and hemoglobin = 10.0 g/dL (= 6.2 mmol/L). b) Hepatic: Bilirubin = 1.5 times the upper limit of normal (x ULN) (or total bilirubin = 3.0 x ULN or direct bilirubin = 1.5 x ULN in patients with well-documented Gilbert's syndrome); alkaline phosphatase (ALP) = 2.5 times ULN; aspartate transaminase (AST) and alanine transami-nase (ALT) = 3 times ULN. c) Renal: Serum creatinine = 1.5
Exclusion criteria
Exclusion criteria: 1. Metastatic progression (M1, according to TNM staging system). 2. Substantial nodal involvement (N>2, according to TNM staging system). 3. Non-large tumor (T0-1, according to TNM staging system). 4. Bilateral breast carcinoma. 5. Inflammatory carcinoma (T4d, according to TNM staging system). 6. Patients with exclusive non-measurable/evaluable disease. 7. Known hypersensitivity to any palbociclib excipients. 8. Known hypersensitivity to any letrozole excipients. 9. Formal contraindication to endocrine therapy. 10. Patients unable to swallow tablets. 11. Other malignancies within the past five years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix. 12. Previous radiotherapy on the ipsilateral chest wall for the treatment of any other malignance. 13. Major surgery (defined as requiring general anesthesia) or significant traumatic injury within four weeks of start of study treatment, or 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. 14. Have a serious concomitant systemic disorder (i.e., active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator). 15. Patients with an active bleeding diathesis, 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). 16. History of malabsorption syndrome or other condition that would interfere with enteral absorption. 17. Chronic daily treatment with corticosteroids with a dose of = 10 mg/day methylpredniso-lone equivalent (excluding inhaled steroids). 18. QTc interval > 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). 19. Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (i.e., hypocalcemia, hypokalemia, or hypomagnesemia). 20. Participation in the treatment phase of an interventional trial within 30 days prior to study treatment start.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To explore after 6 months of treatment the ability of palbociclib in combination with letro-zole to induce global molecular changes measured by either the Oncotype DX Breast Recurrence Score® (the “Assay”) test result at surgery (post-treatment Recurrence Score® (RS) result), or pathological Complete Response (pCR) in patients with aggres-sive luminal tumors (pre-treatment RS result 18-25 or 26-100, and Ki67>20).;Secondary Objective: -Explore ability of palbociclib plus letrozole to induce global molecular changes post-treatment RS result after treatment -Explore ability of combination to induce global molecular reduction measured by either the post-treatment RS result, and/or Residual Cancer Burden (RCB), and/or Ki67 after treatment. -Verify ability to induce global molecular reduction (measured as either post-treatment RS=25 or RCB score of 0-I) in >35% in cohort B and ability to induce increase in RS result (measured as post-treatment RS 26-100) in <3% in cohort A -Concordance rate between the RCB score (0-I vs.II-III) and the post-treatment RS result. Concordance rate between the preoperative endocrine prognostic index (PEPI) score and post-treatment RS result -Concordance rate between the pCR and the post-treatment RS result -Determine the Overall Response Rate, Duration of Response, Time to Response, Clinical Benefit Rate and Maximum Tumor Shrinkage -Safety and tolerability of palbociclib plus letrozole;Primary end point(s): 1. The percentage of patients in cohort A that experience a stable RS result as measured by the Assay after 6 months of treatment: from pre-treatment RS 18-25 to post-treatment RS=25; or (*) 2. The percentage of patients in cohort B that experience a change in RS result after 6 months of treatment: from pre-treatment RS 26-100 to post-treatment RS=25; or (*) (*) The percentage of patients with pre-treatment RS 18-25 or 26-100 that experience a biological response after 6 months of treatment defined by pCR (invasive) or micr | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): BIOLOGY o The percentage of patients that experience a biological response after 6 months of treatment defined by any of the three following parameters: - Change in RS result: from pre-treatment RS 18-25 to post-treatment RS 0-17 for patients in cohort A and from pre-treatment RS 26-100 to post-treatment RS=25 for patients in cohort B; And/Or - Change in RCB score, which is calculated combining pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size): from pre-treatment score of II-III to post-treatment score of 0-I for both cohorts of pa-tients; And/Or - Change in Ki67: from Ki67 >20 to 10% and Ki67 <2.7 evaluated on tissue biopsy at 14 days. Median absolute value or median percentage of change in RS result from pre-treatment to post-treatment RS results in both cohorts of patients after 6 months of treatment. EFFICACY o ORR, defined as the number of patients with complete response (CR) and partial response (PR) divided by the number of patients in the analysis population. Tumor re-sponse will be defined as best response, based on local investigator’s assessment ac-cording to RECIST v.1.1. o DoR, defined as the time from documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurs first, as assessed by the Investigator per RECIST v.1.1. o TTR: is defined as the time from study initiation to the first overall tumor response (tumor shrinkage of =30%) observed for patients who achieved a CR or PR. 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 RECIST v1.1. o CBR as best response, defined as the percentage of patients who experience a CR, PR or SD for at least 24 weeks and assessed by the Investigator per RECIST v.1.1. o Maximum Tumor Shrinkage defined as the percentage of tumor shrinkage from baseline, based on local investigator’s | — |
Countries
Spain
Contacts
Public ContactLaura Calabuig
Medica Scientia Innovation Research (MedSIR)
Outcome results
None listed