eoadjuvant Biomarker ResearcH Study of Palbociclib Combined with Endocrine Therapy in Estrogen Receptor Positive/ HER2 Negative Breast CAncer

Phase 1

• Conditions: Primary breast cancer; MedDRA version: 20.0Level: LLTClassification code 10006192Term: Breast cancer NOSSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-000879-24-BE
• Lead Sponsor: Institut Jules Bordet

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-02-15
• Last Update Posted: 23 July 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 110

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 < 4 signals/cells OR ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells [without IHC]; note: a IHC of 3+ is always considered HER2 positive, independently of the ISH result.
5. A primary non metastatic or locally advanced tumour of =15 mm or more, assessed by ultrasound, N0 or N1 without prior treatment candidate for preoperative treatment
6. ECOG Performance Status (PS) 0 or 1.
7. Adequate Bone Marrow Function including:
a. Absolute Neutrophil Count (ANC) =1500/µL or =1.5 x109/L;
b. Platelets =100000/µL or =100 x 109/L;
c. Hemoglobin = 9 g/dL.
8 Adequate Renal Function including: Serum creatinine = 1.5 x upper limit of normal (ULN) or estimated creatinine clearance = 60 ml/min as calculated using the method standard for the institution.
9. Adequate Liver Function, including all of the following parameters:
a. Total serum bilirubin = 1.0 x ULN unless the subject has documented Gilbert syndrome (in which case up to 3 x ULN is acceptable);
b. Aspartate and Alanine Aminotransferase (AST and ALT) = 1.5 x ULN;
c. Alkaline phosphatase = 2.5 x ULN.
10. Signed consent form
11. Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests, radiological exams, tumour and blood specimen collection and other procedures.
12. Women who are not postmenopausal or have not undergone hysterectomy must have documented negative pregnancy test (serum) prior to inclusion.
13. Female subjects of child bearing potential and their partners, who are sexually active, must agree to the use of one highly effective non hormonal form of contraception throughout the period of taking study treatment and for at least 90 days after last dose of study drug, or they must totally/truly abstain from any form of sexual intercourse. Use of oral hormonal contraceptive agents in this study is not permitted.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified