Condition category
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Contact information



Primary contact

Ms Leona Batten


Contact details

ICR Clinical Trials and Statistics Unit
15 Cotswold Road
United Kingdom

Additional identifiers

EudraCT number

2014-000887-16 number


Protocol/serial number


Study information

Scientific title

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



Study hypothesis

PALLET will evaluate whether adding palbociclib to standard hormone therapy with letrozole is better than using letrozole alone at treating breast cancer before surgery.

Ethics approval

London-Fulham REC, 01/09/2014, ref. 14/ LO/ 1291

Study design

Randomised; Interventional

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Post-menopausal patients with ER+ and HER2- primary breast cancer


1. Palbociclib is an unlicensed drug that is a 125mg capsule that should be administered orally. The treatment schedule is 3 weeks on, 1 week off.
2. Letrozole is a 2.5mg tablet that will be administered orally on a daily basis. Both drugs will be taken for up to 14 weeks, depending on treatment arm. Patients will be followed up for 1 year after date of randomisation.

Intervention type



Phase II

Drug names


Primary outcome measures

1. Change in the proliferation marker Ki67 (% positive tumour cells) as tested by IHC from baseline to after 14 weeks treatment with letrozole with or without palbociclib
2. Clinical response as measured by ultrasound according to ECOG criteria after 14 weeks treatment with letrozole with or without palbociclib

Secondary outcome measures

1. Effect of palbociclib on Ki67 after 2 weeks and the added effect of letrozole from weeks 2-14 (within group)
2. Effect of letrozole on Ki67 after 2 weeks and the added effect of palbociclib from weeks 2-14 (within group)
3. pCR rates after letrozole with or without 14 weeks palbociclib
4. PEPI score after letrozole with or without 14 weeks palbociclib
5. Assessment of safety and tolerability

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Postmenopausal women defined as:
1.1. Age 56 or older with no spontaneous menses for at least 12 months prior to study entry
1.2. Age 55 or younger with no menses for at least 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) and with a documented oestradiol level in the postmenopausal range according to local institutional/laboratory standard
1.3. Age ≥16 with documented bilateral oophorectomy
2. Operable ER+ HER2- invasive early breast cancer suitable for neoadjuvant AI treatment. HER2 negativity will be defined as per the 2013 ASCO/CAP guidelines as follows:
2.1. IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within >10% of the invasive tumour cells
2.2. 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
2.3. ISH negative based on:
2.3.1. Single-probe average HER2 copy number <4.0 signals/cell
2.3.2. 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:
7.1.Haemoglobin >10g/dL (90g/L)
7.2. ANC ≥ 1,500/ mm³ (> 1.5 x 109/L)
7.3. Platelets >100,000/mm³ (> 100 x 109/L)
7.4. AST and/or ALT 1.5 x upper normal limits (ULN)
7.5 Alkaline phosphatase 1.5 x ULN
7.6. 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
7.7. Serum creatinine <1.25 x ULN or estimated creatinine clearance < 60 mL/min (as calculated using the method standard for the institution)
7.8. No severe and relevant co-morbidity that would affect a patient’s participation in the study
7.9. 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 (fresh tissue and surplus tissue from diagnostic procedures) and blood samples
9. Patients must have the ability to swallow oral medication

Participant type


Age group




Target number of participants

Planned Sample Size: 306; UK Sample Size: 150

Participant 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. Any invasive malignancy within previous 5 years (other than basal cell carcinoma or cervical carcinoma in situ)
7. Any severe coincident medical disease, including seizure disorder requiring medication
8. Diagnosis by FNA alone or excisional biopsy or lumpectomy performed prior to study entry
9. Surgical axillary staging procedure prior to study procedure (with the exception of FNA or core biopsy)
10. Definitive clinical or radiologic evidence of metastatic disease
11. History of ipsilateral invasive breast cancer regardless of treatment or ipsilateral DCIS treated with radiotherapy or contralateral invasive breast cancer at any time
12. New York Hearth Association classification of level III or IV heart disease
13. Any treatment, including radiotherapy, chemotherapy, and/or targeted therapy, administered for the currently diagnosed breast cancer prior to study entry
14. Patients on established CYP3A inhibitors/inducers
15. QTc >480 msec or a family or personal history of long or short QT syndrome, Brugada syndrome or know history of QTc prolongation, or Torsade de Pointes (TdP)
16. Active Hepatitis B or Hepatitis C with abnormal liver function tests
17. HIV positive patients receiving antivirals

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

ICR Clinical Trials and Statistics Unit
15 Cotswold Road
United Kingdom

Sponsor information


The Institute for Cancer Research

Sponsor details

Section of Clinical Trials
15 Cotswold Road
United Kingdom

Sponsor type

Hospital/treatment centre



Funder type


Funder name

Pfizer Inc. (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

14/01/2016: Internal corrections.