eo-Adjuvant Treatment with the CDK4,6 inhibitor Palbociclib in HER2-positive and ER-positive breast cancer: effect on Ki67 and apoptosis before, during and after treatment

• Conditions: Women with a diagnosis of invasive unilateral non metastaticHER2-positive and ER-positive breast cancer suitable forneoadjuvant therapy; MedDRA version: 17.1Level: LLTClassification code 10006283Term: Breast neoplasm malignant femaleSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-001984-11-IT
• Lead Sponsor: FONDAZIONE MICHELANGELO - AVANZAMENTO DELLO STUDIO E DELLA CURA DEI TUMORI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-10-28
• Last Update Posted: 9 March 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 32

Inclusion Criteria

1. Female patients aged 18 years or older with tumors
suitable for neoadjuvant treatment
2. Early (> 1.5 cm) or locally advanced untreated breast
cancer
3. Histologically confirmed invasive unilateral breast cancer
4. HER2-positive disease centrally confirmed
5. Positive estrogen receptor (ER) > 10% and known
progesterone receptor (PgR)
6. Available paraffin-embedded tumor block taken at
diagnostic biopsy for central retrospective confirmation of
HER2 and ER eligibility and for assessment of Ki67 value
and apoptosis is mandatory
7. All patients must agree to provide tumor tissues for
centralized assessment of KI67 values and apoptosis at the
required timelines (2 weeks from starting protocol therapy
and at surgery)
8. ECOG performance status 0 or 1
9. Written informed consent to participate in the trial
(approved by the Institutional Review Board [IRB]/
Independent Ethics Committee [IEC]) obtained prior to any
study specific screening procedures
10. Willing and able to comply with the protocol
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 32
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32

Exclusion Criteria

1. Evidence of bilateral invasive breast cancer or metastatic disease (M1)
2. Pregnant or lactating women. Documentation of a negative serum pregnancy test must be available for premenopausal women with intact reproductive organs and for women less than one year after the last menstrual cycle
3. Women with childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception, for example abstinence, an intra-uterine device, or double barrier method of contraception up to 7 months from the last dose of either anticancer study drug
4. Previous treatment with chemotherapy, hormonal therapy or an investigational drug for any type of malignancy
5. Previous extensive radiotherapy
6. Previous investigational treatment for any condition within 4 weeks of registration date
7. Known hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol
8. Previous or concomitant malignancy of any other type that could affect compliance with the protocol or interpretation of results. Patients with curatively treated basal cell carcinoma of the skin, stage 1 uterine cancer or in situ cervix cancer are generally eligible.
9. Other serious illness or medical condition including: history of documented congestive cardiac failure; angina pectoris requiring anti-anginal medication; evidence of transmural infarction on ECG; poorly controlled hypertension (e.g. systolic >180 mm Hg or diastolic >100 mm Hg; however, patients with hypertension which is well controlled on medication are eligible); clinically significant valvular heart disease; high-risk uncontrolled arrhythmias
10. Baseline left ventricular ejection fraction (LVEF) < 55% by echocardiography or multi-gated scintigraphic scan (MUGA)
11. QTc >480 msec or a family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP)
12. Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and precluding informed consent or adversely affecting compliance with study drugs
13. Serious uncontrolled infections (bacterial or viral) or poorly controlled diabetes mellitus
14. Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors or inducers
15. Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia)
16. Any of the following abnormal baseline hematological values:
a.Absolute Neutrophil Count (ANC) < 1.5 ? 109/L
b.Platelet count < 100 ? 109/L
c.Hemoglobin (Hb) < 10 g/dL
17. Any of the following abnormal baseline laboratory tests
a.Serum total bilirubin > 1.5 ? ULN (upper limit of normal) (except for patients with clearly documented Gilbert’s syndrome)
b.Alanine transaminase (ALT) or aspartate transaminase (AST) > 1.25 ? ULN
c.Alkaline phosphatase > 2.5? ULN
d.Serum creatinine > 1.5 ? ULN
e.INR > 2

Study & Design

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