Condition category
Cancer
Date applied
08/01/2015
Date assigned
09/01/2015
Last edited
01/11/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Ms Leona Batten

ORCID ID

Contact details

ICR Clinical Trials and Statistics Unit
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom

Additional identifiers

EudraCT number

2014-000887-16

ClinicalTrials.gov number

NCT01889680

Protocol/serial number

ICR-CTSU/2014/10044

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

Acronym

PALLET

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

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

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

Intervention

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

Drug

Phase

Phase II

Drug names

Palbociclib

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
6. Changes between surgical intent at baseline, surgical intent after 14 weeks and actual surgery received after treatment with letrozole with or without palbociclib (added 01/11/2016)

Overall trial start date

23/02/2015

Overall trial end date

31/08/2018

Reason abandoned

Eligibility

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. ER positivity is defined as an Allred score of 3 (or equivalent) [sentence added 01/11/2016]. 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 and blood samples
9. Patients must have the ability to swallow oral medication

Participant type

Patient

Age group

Adult

Gender

Both

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. Bilateral invasive disease (added 01/11/2016)
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 Hearth 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 know 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

Recruitment start date

23/02/2015

Recruitment end date

31/08/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

ICR Clinical Trials and Statistics Unit
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom

Sponsor information

Organisation

The Institute for Cancer Research

Sponsor details

Section of Clinical Trials
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

Pfizer Inc. (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

01/11/2016: Added new secondary outcome measure and made amendments to inclusion and exclusion criteria (time stamped in relevant section of record). Changed overall end date from 15/12/2017 to 31/08/2018. Changed recruitment end date from 23/08/2016 to 31/08/2017. 14/01/2016: Internal corrections.