Evaluating the biological and clinical effects of the combination of palbociclib with letrozole as neoadjuvant therapy in post-menopausal women with primary breast cancer
| ISRCTN | ISRCTN31243262 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN31243262 |
| EudraCT/CTIS number | 2014-000887-16 |
| ClinicalTrials.gov number | NCT01889680 |
| Secondary identifying numbers | ICR-CTSU/2014/10044 |
- Submission date
- 08/01/2015
- Registration date
- 09/01/2015
- Last edited
- 16/01/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Contact information
Ms Katie Goddard
Scientific
Scientific
ICR Clinical Trials and Statistics Unit
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom
Study information
| Study design | Randomised; Interventional |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| 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 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(s) | London-Fulham REC, 01/09/2014, ref. 14/ LO/ 1291 |
| Condition | Post-menopausal patients with ER+ and HER2- primary breast cancer |
| Intervention | 1. Palbociclib is an unlicensed drug that is a 125-mg capsule that should be administered orally. The treatment schedule is 3 weeks on, 1 week off. 2. Letrozole is a 2.5-mg 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Palbociclib, letrozole |
| Primary outcome measure | 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 study start date | 23/02/2015 |
| Overall study end date | 03/03/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Planned Sample Size: 306; UK Sample Size: 150 |
| 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 patients 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 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 | 08/03/2018 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
ICR Clinical Trials and Statistics Unit
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom
Sutton
SM2 5NG
United Kingdom
Sponsor information
The Institute for Cancer Research
Hospital/treatment centre
Hospital/treatment centre
Section of Clinical Trials
15 Cotswold Road
Sutton
SM2 5NG
England
United Kingdom
"ROR" |
https://ror.org/043jzw605 |
|---|
Funders
Funder type
Industry
Pfizer UK
Private sector organisation / For-profit companies (industry)
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Pfizer Ltd, Pfizer Limited
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from PALLET-icrctsu@icr.ac.uk. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Plain English results | No | Yes | |||
| Results article | results | 20/01/2019 | 26/02/2019 | Yes | No |
| Protocol file | version 2.1 | 24/11/2015 | 16/01/2023 | No | No |
Additional files
Editorial Notes
16/01/2023: Protocol file uploaded.
15/04/2021: The overall trial end date was changed from 30/09/2019 to 03/03/2020.
04/09/2020: Cancer Research UK lay results summary link added to Results (plain English).
05/04/2019: IPD sharing statement added.
26/02/2019: Contact details updated, publication reference added.
15/03/2018: The following changes have been made:
1.Recruitment end date changed from 31/08/2017 to 08/03/2018
2.Overall trial end date changed from 31/08/2018 to 30/09/2019
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.
