Primary breast cancer MedDRA version: 20.0 Level: LLT Classification code 10006192 Term: Breast cancer NOS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: IBRANCE
Pharmaceutical Form: Capsule
INN or Proposed INN: PALBOCICLIB
CAS Number: 571190-30-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Trade
Sponsors
Institut Jules Bordet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria in order to be eligible for this study: 1. Female. 2. Age = 18 years 3. Histological diagnosis of breast adenocarcinoma that is estrogen receptor-positive, and HER2- negative as per the updated American Society of Clinical Oncology (ASCO) - College of American Pathologists (CAP) guidelines according to local testing. 4. Multifocal unilateral or bilateral breast adenocarcinoma tumours are allowed provided that all tested foci are: - ER-positive (ER+ is defined as having a IHC of 1% or more and/or and Allred of 3 or more and HER2-negative). - HER2 negative (HER2 negative is defined as having an IHC of 0 or 1+ without ISH OR IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: Subjects meeting one of the following criteria are not eligible for this study: 1. Clinical T4 disease including inflammatory breast cancer. 2. Prior history of invasive cancer including breast cancer except basal or squamous cell carcinoma of skin that has been definitively treated. 3. Known hypersensitivity to the study drug or excipients. 4. Any illness or medical condition that is unstable or could jeopardize the safety of the subject or her compliance with study requirements. 5. Subjects unable to swallow oral medications. 6. Prior intake of letrozole, tamoxifen or any CDK inhibitor or anti-cancer therapy. 7. Concurrent treatment with any of the drugs not permitted, i.e. strong CYP3A inhibitors/inducers and drugs known to cause QT interval prolongation; (see section 5.7 for specific instructions). 8. QTc exceeding 480 msec, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP). 9. Uncontrolled diabetes, according to investigator’s clinical judgment. 10. Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To identify biomarkers of resistance to a 4-month preoperative treatment of palbociclib plus endocrine therapy defined as stable or progressive disease by ultrasound (based on WHO criteria) using RNA-seq of the baseline tumour biopsy.;Secondary Objective: To identify biomarkers of resistance to a 4-month preoperative treatment of endocrine therapy and palbociclib by correlating tumour response by ultrasound (mandatory) or magnetic resonance (optional) imaging (response will be assessed as continuous or categorical variable) with RNA-seq of the baseline tumour biopsy To identify biomarkers of resistance to a 4-month preoperative treatment defined as residual disease burden, RCB of 3 using RNA-seq of the baseline tumour biopsy To identify biomarkers of resistance to a 4-month preoperative treatment defined as GGI high by RNA-seq of the leftover tumour at surgery using RNA-seq of the baseline tumour biopsy To understand mechanisms of resistance to the combination by comparing the transcriptome of tumours at baseline and at surgery using RNA-seq To determine the effect of a pre-operative treatment on anti-tumour immune response To determine the effect of a pre-operative treatment on tumour senescence. ;Primary end point(s): Baseline transcriptomic profile of resistance to 4 months of palbociclib and endocrine therapy defined as stable or progressive disease by ultrasound based on WHO criteria;Timepoint(s) of evaluation of this end point: After the last treatment of the last patient | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Baseline transcriptomic profile of resistance to 4 months of palbociclib and endocrine therapy assessed by ultrasound (mandatory) or magnetic resonance (optional) imaging (response will be assessed as continuous or categorical variable) • Baseline transcriptomic profile of resistance to 4 months of palbociclib and endocrine therapy, defined as an RCB of 3. • Baseline transcriptomic profile of resistance to 4 months of palbociclib and endocrine therapy, defined as an GGI high at surgery • Transcriptomic changes between pre-treatment and post-treatment tumour samples • Safety • Plasma ctDNA analysis to monitor response/resistance to pre-operative treatment with endocrine therapy and palbociclib • Validation of 11-gene expression signature associated with response/resistance to palbociclib and endocrine treatment • Changes in anti-tumour immune response between pre- and post-treatment tumour samples; • Changes in tumour senescence between pre- and post-treatment tumour samples. ;Timepoint(s) of evaluation of this end point: After the last treatment of the last patient | — |
Countries
Belgium
Contacts
Public ContactCTSU
Institut Jules Bordet
Outcome results
None listed