A phase II randomised study evaluating the biological and clinical effects of the combination of palbociclib with letrozole as neoadjuvant therapy in post-menopausal women with ER+ primary breast cancer.

Phase 1

• Conditions: ER positive, HER2 negative early invasive breast cancer; MedDRA version: 18.1Level: PTClassification code 10057654Term: Breast cancer femaleSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-000887-16-GB
• Lead Sponsor: The Royal Marsden NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-03-04
• Last Update Posted: 8 June 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 306

Inclusion Criteria

1. Postmenopausal women defined as:
i. Age 56 or older with no spontaneous menses for at least 12 months prior to study entry; or
ii. Age 55 or younger with no menses for at least 12 months prior to study entry (e.g., spontaneous or after hysterectomy) and with a documented oestradiol level in the postmenopausal range according to local institutional/laboratory standard; or
iii. Age =16 with documented bilateral oophorectomy
2. Operable ER+ HER2- invasive early breast cancer suitable for neoadjuvant AI treatment. ER positivity is defined as an Allred score of 3 (or equivalent). HER2 negativity will be defined as per the 2013 ASCO/CAP guidelines as follows:
i. IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within >10% of the invasive tumour cells; or
ii. IHC 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within =10% of the invasive tumour cells; or
iii. ISH negative based on:
o Single-probe average HER2 copy number <4.0 signals/cell
o Dual-probe HER2/CEP17 ratio <2.0 with an average HER2 copy number <4.0 signals/cell
3. No medical contra-indication to palbociclib (as defined according to latest version of Investigator Brochure)
4. A tumour with an ultrasound size of at least 2.0cm
5. No evidence of metastatic spread by standard assessment according to local guidelines
6. ECOG performance status of 0 or 1
7. Adequate organ function including:
a) haemoglobin =10g/dL (100g/L)
b) ANC = 1,500/mm³ (> 1.5 x 10^9/L)
c) platelets =100,000/mm³ (> 100 x 10^9/L)
d) AST and/or ALT <1.5 x x upper normal limits (ULN)
e) Alkaline phosphatase <1.5 x ULN
f) total serum bilirubin < ULN unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin
g) serum creatinine =1.25 x ULN or estimated creatinine clearance > 60 mL/min (as calculated using the method standard for the institution)
h) no severe and relevant co-morbidity that would effect a patient’s participation in the study
i) INR must be within normal limits of the local laboratory ranges
8. Written informed consent to participate in the trial and to donation of tissue and blood samples
9. Patients must have the ability to swallow oral medication
Are the trial subjects under 18? yes
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

1. Premenopausal or perimenopausal women
2. Inflammatory/inoperable breast cancer
3. HER2 positive
4. Concurrent use (defined as use within 4 weeks prior to baseline tissue sample being taken) of HRT or any other oestrogen-containing medication (including vaginal oestrogens)
5. Prior endocrine therapy for breast cancer
6. Bilateral invasive disease
7. Any invasive malignancy within previous 5 years (other than basal cell carcinoma or cervical carcinoma in situ)
8. Any severe coincident medical disease, including seizure disorder requiring medication
9. Diagnosis by FNA alone or excisional biopsy or lumpectomy performed prior to study entry
10. Surgical axillary staging procedure prior to study procedure (with the exception of FNA or core biopsy)
11. Definitive clinical or radiologic evidence of metastatic disease
12. History of ipsilateral invasive breast cancer regardless of treatment or ipsilateral DCIS treated with radiotherapy or contralateral invasive breast cancer at any time
13. New York Heart Association classification of level III or IV heart disease
14. Any treatment, including radiotherapy, chemotherapy, and/or targeted therapy, administered for the currently diagnosed breast cancer prior to study entry
15. Patients on established CYP3A inhibitors/inducers
16. 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).
17. Active Hepatitis B or Hepatitis C with abnormal liver function tests.
18. HIV positive patients receiving antivirals.

Study & Design

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