Persephone: duration of Herceptin with chemotherapy 6 versus 12 months

ISRCTN	ISRCTN52968807
DOI	https://doi.org/10.1186/ISRCTN52968807
ClinicalTrials.gov (NCT)	NCT00712140
Clinical Trials Information System (CTIS)	2006-007018-39
Protocol serial number	HTA 06/303/98
Sponsor	Cambridge Hospitals NHS Foundation Trust and Cambridge University (UK)
Funder	NIHR Health Technology Assessment Programme - HTA (UK)

Submission date: 09/02/2007
Registration date: 13/02/2007
Last edited: 07/09/2020

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 of protocol

http://www.cancerhelp.org.uk/trials/a-trial-comparing-6-months-and-12-months-of-trastuzumab-for-early-breast-cancer

Contact information

Dr Helena Earl
Scientific

Oncology Department
Box 193
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Phone	+44 (0)1223 274312
Email	hme22@cam.ac.uk

Study information

Primary study design	Interventional
Study design	Phase III randomised multi-centre trial
Secondary study design	Randomised controlled trial
Scientific title	Persephone: duration of Herceptin with chemotherapy 6 versus 12 months
Study acronym	Persephone
Study objectives	Does 6 months of trastuzumab (Herceptin®) treatment prevent breast cancer relapse (disease-free survival [DFS]) as well as 12 months of trastuzumab treatment? To test the hypothesis that reducing the duration of adjuvant trastuzumab to 6 months from 12 months, in 4,000 patients (updated 08/10/2014: originally women only) with HER-2 positive early breast cancer, produces equivalent (non-inferior) disease-free and overall survival outcomes. More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/0630398 Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0016/51334/PRO-06-303-98.pdf On 15/01/2008 the overall trial end date was changed from 01/04/2011 to 31/03/2013. On 08/10/2014 the overall trial end date was changed from 30/09/2014 to 30/06/2015.
Ethics approval(s)	North West Research Ethics Committee, 09/08/2007, ref: 07/MRE08/35
Health condition(s) or problem(s) studied	HER2-positive early breast cancer
Intervention	Current interventions as of 08/10/2014: Patients will receive during or after a standard regimen of chemotherapy either: 1. The standard treatment, i.e. a dose every 3 weeks for a year (18 doses) or 2. The research treatment, i.e. 9 doses over 6 months The starting dose of IV trastuzumab is 8 mg/kg. The maintenance dose is 6 mg/kg. All doses of sub-cut trastuzumab are 6 mg/kg. Previous interventions: Patients will receive during or after a standard regimen of chemotherapy either: 1. The standard treatment, i.e. a dose every 3 weeks for a year (17 doses) or 2. The research treatment, i.e. 9 doses over 6 months The starting dose of trastuzumab is 8 mg/kg. The maintenance dose is 6 mg/kg.
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Herceptin (trastuzumab)
Primary outcome measure(s)	Disease-free survival non-inferiority (equivalence) of 6 months trastuzumab to 12 months in early breast cancer
Key secondary outcome measure(s)	1. Does 6 months of trastuzumab treatment prevent breast cancer death as well as 12 months of trastuzumab treatment? 2. What is the health economic costs and the quality of life for patients receiving 6 months versus 12 months of trastuzumab treatment? Research will also be conducted through the collection of tissue samples Updated 08/10/2014: Research will also be conducted through the collection of blood and tissue samples
Completion date	30/06/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target sample size at registration	4000
Total final enrolment	4089
Key inclusion criteria	1. Histological diagnosis of invasive breast cancer 2. No evidence of metastatic disease 3. Known hormone receptor status 4. Overexpression of HER-2 positive: 3+ overexpression by immunohistochemistry (IHC) or 2+ overexpression by IHC and fluorescence in situ hybridisation (FISH) test positive 5. Clear indication for chemotherapy based on clinical and histopathological features 6. Patient fit to receive any of the trial chemotherapy regimens 7. Patient must not have clinically significant cardiac abnormalities and must not have had a previous myocardial infarction during the 6 months prior to recruitment. Cardiac function should be assessed by physical examination and electrocardiogram (ECG) 8. Patient must have adequate bone marrow, hepatic, and renal function 9. No previous chemotherapy or radiotherapy 10. No previous diagnosis of malignancy unless: 10.1. Managed by surgical treatment only, and disease-free for 10 years 10.2. Previous basal cell carcinoma, cervical carcinoma in situ or ductal carcinoma in situ of the breast treated by surgery only 11. Non-pregnant and non-lactating 12. No concomitant medical or psychiatric problems that might prevent completion of treatment or follow-up 13. Patients 18 years or older (updated 08/10/2014; originally women only) 14. Written informed consent for the study
Key exclusion criteria	1. Non-controlled or malignant arterial high-pressure 2. Clinically significant cardiac disease. Cardiac left ventricular ejection fraction below normal range 3. History of atrio-ventricular arrhythmias and/or congestive heart failure, even where it is under medical control, or active second- or third-degree cardiac block. History of myocardial infarct during the 6 months prior to recruitment. 4. Any co-morbidity significantly adding to risks associated with cytotoxic chemotherapy, for instance: severe chronic obstructive pulmonary disease, poorly controlled diabetes, etc. 5. History of allergy to drugs containing polysorbate 20 and the excipient TWEEN 80® and history of allergy to mouse proteins 6. Inability to comply with protocol requirements
Date of first enrolment	04/10/2007
Date of final enrolment	30/06/2015

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Addenbrooke's Hospital

Cambridge
CB2 0QQ
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	20/05/2014		Yes	No
Results article	results	29/06/2019	11/06/2019	Yes	No
Results article	results	01/08/2020	07/09/2020	Yes	No
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

07/09/2020: Publication reference added.
11/06/2019: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.