Breast CancerPhase 3NCT00712140
Trastuzumab in Treating Women With HER2-Positive Early Breast Cancer
A Phase 3 study testing trastuzumab and parenteral chemotherapy in people with Breast Cancer, run by Warwick Medical School at 11 sites in United Kingdom.
Trial summary
RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- trastuzumab and parenteral chemotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4,000 participants
- Where
- 11 sitesUnited Kingdom
- Study dates
- Oct 2007to Oct 2011
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed invasive breast cancer
- No evidence of metastatic disease
- Overexpression of HER2 receptor defined as 3+ or 2+ HER2 positivity measured by fluorescent in situ hybridization (FISH) gene amplification
- Indication for chemotherapy based on the following clinical and histopathological features:
- Receiving or scheduled to receive neoadjuvant chemotherapy
- Time between diagnosis biopsy and start date of chemotherapy should be less than 1 month
- Receiving or scheduled to receive adjuvant chemotherapy
- Completely resected disease, with negative surgical margins (apart from deep margin if full thickness resection)
- Marginally resected disease and/or positive sentinel nodes allowed provided patients undergo completion of surgery (breast and/or axillary clearance) after chemotherapy
- Hormone receptor status known
PATIENT CHARACTERISTICS:
- Menopausal status not specified
- ECOG performance status 0-1
- Adequate bone marrow, hepatic, and renal function
- LVEF normal by ECHO or MUGA
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No clinically significant cardiac abnormalities
- No myocardial infarction within the past 6 months
- No uncontrolled or malignant hypertension
- No history of atrioventricular arrhythmia and/or congestive heart failure (even under medical control), or active second or third degree cardiac block
- No history of allergy to drugs containing polysorbate 20 and the excipient polysorbate 80 (TWEEN 80®) or history of allergy to mouse proteins
- No co-morbidity significantly adding to risks associated with cytotoxic chemotherapy (i.e., severe chronic obstructive pulmonary disease or poorly controlled diabetes)
- No prior diagnosis of malignancy unless managed by surgical treatment only and disease-free for 10 years
- Prior basal cell carcinoma, cervical carcinoma in situ, or ductal carcinoma in situ of the breast allowed if treated by surgery only
- No concomitant medical or psychiatric problems that might preclude completion of treatment or follow-up
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior chemotherapy or radiotherapy
- Concurrent radiotherapy allowed
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United Kingdom11 sites, 11 recruiting
- Recruiting
Aberdeen Royal Infirmary
Aberdeen, Scotland, AB25 2ZN
Contact Person, 44-84-5456-6000
- Recruiting
Addenbrooke's Hospital
Cambridge, England, CB2 2QQ
Helena Earl, MBBS, PhD, FRCP, 44-1223-336-800
- Recruiting
Cumberland Infirmary
Carlisle, England, CA2 7HY
Contact Person, 44-1228-523-444
- Recruiting
Derbyshire Royal Infirmary
Derby, England, DE1 2QY
Contact Person, 44-1332-347-141 ext. 2407
- Recruiting
Eastbourne District General Hospital
Eastbourne, England, BN21 2UD
Contact Person, 44-1323-417-400
- Recruiting
Luton and Dunstable Hospital
Luton, England, LU4 0DZ
Contact Person, 44-845-127-0127
- Recruiting
Clatterbridge Centre for Oncology
Merseyside, England, CH63 4JY
Contact Person, 44-151-334-1155
- Recruiting
James Cook University Hospital
Middlesbrough, England, TS4 3BW
Contact Person, 44-1642-850-850
- Recruiting
Mount Vernon Cancer Centre at Mount Vernon Hospital
Northwood, England, HA6 2RN
Contact Person, 44-1923-826-111
- Recruiting
Peterborough Hospitals Trust
Peterborough, England, PE3 6DA
Contact Person, 44-1733-874-510
- Recruiting
New Cross Hospital
Wolverhampton, England, WV10 0QP
Contact Person, 44-190-230-7999
About this study
Official title: Persephone: Duration of Trastuzumab With Chemotherapy in Women With Early Stage Breast Cancer: Six Months Versus Twelve
RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known which regimen of trastuzumab is more effective in treating early breast cancer.
PURPOSE: This randomized phase III trial is comparing two trastuzumab regimens to see how well they work in treating women with HER2-positive early breast cancer.
Read the detailed description
OBJECTIVES:
Primary
- Determine disease-free survival of women with HER2-positive early breast cancer treated with neoadjuvant or adjuvant trastuzumab (Herceptin®) for 6 months versus 12 months.
Secondary
- Determine the overall survival of patients treated with these regimens.
- Determine the expected incremental cost effectiveness (cost per quality adjusted life year gained) for 6 months versus 12 months trastuzumab.
- Determine cardiac function as assessed by left ventricular ejection fraction every 3 months during treatment.
- Analyze the predictive factors for development of cardiac damage.
OUTLINE: This is a multicenter study. Patients are stratified according to estrogen receptor status (negative vs positive); chemotherapy timing (adjuvant vs neoadjuvant); chemotherapy type (anthracycline based [no taxane] vs taxane and anthracyclines vs taxane-based [no anthracyclines]); and trastuzumab (Herceptin®) timing (concurrently vs sequentially [with respect to chemotherapy]). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity.
All patients also receive standard chemotherapy regimens as per local institutional protocols either concurrently with or sequentially to trastuzumab.
Patients complete quality of life questionnaires using the EuroQoL-5D (EQ-5D) at baseline and periodically during study treatment. Patients also complete a diary on out-of-pocket expenses associated with their condition (i.e., travel expenses, over-the-counter medicines and supplements, complementary therapies not funded by NHS, home help, and time away from work) for cost-effective analysis.
After completion of study therapy, patients are followed every 3 months for 1 year, then every 6 months for 1 year, and annually thereafter.
- Conditions
- Breast Cancer
- Being tested
- trastuzumab, parenteral chemotherapy
- Keywords
- stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer, HER2-positive breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
trastuzumabBiological
Given IV
parenteral chemotherapyDrug
per the local institutional protocols either concurrently with or sequentially to trastuzumab
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Active comparator | Patients receive trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. All patients also receive standard chemotherapy regimens as per local institutional protocols either concurrently with or sequentially to trastuzumab. Receives: Biological: trastuzumab; Drug: parenteral chemotherapy |
| Arm II | Experimental | Patients receive trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity. All patients also receive standard chemotherapy regimens as per local institutional protocols either concurrently with or sequentially to trastuzumab. Receives: Biological: trastuzumab; Drug: parenteral chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free survival
Secondary outcomes (3)
Overall survival
Cost effectiveness and quality of life
Cardiac function and analysis of predictive factors for development of cardiac damage
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2008 (estimated)
- Study startOct 2007
- Primary completionOct 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Enrolment
- 4,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Warwick Medical School
- Sponsor type
- University, hospital or other
- Investigators
- Helena Earl, MBBS, PhD, FRCP, Principal investigator, Cambridge University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00712140
- Sponsor's protocol ID
- CDR0000598391
- Other IDs
- WMS-PERSEPHONE, MREC-PERSEPHONE, EUDRACT: 2006-007018-39, ISRCTN 52968807, MREC 07/MRE08/35, EU-20858, CRUK-BRD/07/137
- Status last verified
- Nov 2008
- First submitted
- 8 Jul 2008
- Last updated
- 2 Sep 2011
- Results posted
- No
Publications
Earl H, Hiller L, Vallier AL, Loi S, McAdam K, Hughes-Davies L, Rea D, Howe D, Raynes K, Higgins HB, Wilcox M, Plummer C, Mahler-Araujo B, Provenzano E, Chhabra A, Gasson S, Balmer C, Abraham JE, Caldas C, Hall P, Shinkins B, McCabe C, Hulme C, Miles D, Wardley AM, Cameron DA, Dunn JA. Six versus 12 months' adjuvant trastuzumab in patients with HER2-positive early breast cancer: the PERSEPHONE non-inferiority RCT. Health Technol Assess. 2020 Aug;24(40):1-190. doi: 10.3310/hta24400.
PubMed 32880572Earl HM, Hiller L, Vallier AL, Loi S, McAdam K, Hughes-Davies L, Harnett AN, Ah-See ML, Simcock R, Rea D, Raj S, Woodings P, Harries M, Howe D, Raynes K, Higgins HB, Wilcox M, Plummer C, Mansi J, Gounaris I, Mahler-Araujo B, Provenzano E, Chhabra A, Abraham JE, Caldas C, Hall PS, McCabe C, Hulme C, Miles D, Wardley AM, Cameron DA, Dunn JA; PERSEPHONE Steering Committee and Trial Investigators. 6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial. Lancet. 2019 Jun 29;393(10191):2599-2612. doi: 10.1016/S0140-6736(19)30650-6. Epub 2019 Jun 6.
PubMed 31178152
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Persephone: Duration of Trastuzumab With Chemotherapy in Women With Early Stage Breast Cancer: Six Months Versus Twelve
- ClinicalTrials.gov ID
- NCT00712140
- Acronym / sponsor ID
- CDR0000598391
- Conditions
- Breast Cancer
- Keywords
- stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer, HER2-positive breast cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 4,000 participants (estimated)
- Lead sponsor
- Warwick Medical SchoolUniversity, hospital or other
- Study start
- Oct 2007
- Primary completion
- Oct 2011 (estimated)
- First posted
- 9 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known which regimen of trastuzumab is more effective in treating early breast cancer.
PURPOSE: This randomized phase III trial is comparing two trastuzumab regimens to see how well they work in treating women with HER2-positive early breast cancer.
Detailed description
OBJECTIVES:
Primary
- Determine disease-free survival of women with HER2-positive early breast cancer treated with neoadjuvant or adjuvant trastuzumab (Herceptin®) for 6 months versus 12 months.
Secondary
- Determine the overall survival of patients treated with these regimens.
- Determine the expected incremental cost effectiveness (cost per quality adjusted life year gained) for 6 months versus 12 months trastuzumab.
- Determine cardiac function as assessed by left ventricular ejection fraction every 3 months during treatment.
- Analyze the predictive factors for development of cardiac damage.
OUTLINE: This is a multicenter study. Patients are stratified according to estrogen receptor status (negative vs positive); chemotherapy timing (adjuvant vs neoadjuvant); chemotherapy type (anthracycline based [no taxane] vs taxane and anthracyclines vs taxane-based [no anthracyclines]); and trastuzumab (Herceptin®) timing (concurrently vs sequentially [with respect to chemotherapy]). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity.
All patients also receive standard chemotherapy regimens as per local institutional protocols either concurrently with or sequentially to trastuzumab.
Patients complete quality of life questionnaires using the EuroQoL-5D (EQ-5D) at baseline and periodically during study treatment. Patients also complete a diary on out-of-pocket expenses associated with their condition (i.e., travel expenses, over-the-counter medicines and supplements, complementary therapies not funded by NHS, home help, and time away from work) for cost-effective analysis.
After completion of study therapy, patients are followed every 3 months for 1 year, then every 6 months for 1 year, and annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Active comparator | Biological: trastuzumab, Drug: parenteral chemotherapyPatients receive trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. All patients also receive standard chemotherapy regimens as per local institutional protocols either concurrently with or sequentially to trastuzumab. |
| Arm II | Experimental | Biological: trastuzumab, Drug: parenteral chemotherapyPatients receive trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity. All patients also receive standard chemotherapy regimens as per local institutional protocols either concurrently with or sequentially to trastuzumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| trastuzumabGiven IV | Biological | Arm I, Arm II |
| parenteral chemotherapyper the local institutional protocols either concurrently with or sequentially to trastuzumab | Drug | Arm I, Arm II |
Primary outcome
Disease-free survival
3 secondary outcomes
Overall survival
Cost effectiveness and quality of life
Cardiac function and analysis of predictive factors for development of cardiac damage
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2011.
- Derived from this study: PubMed 32880572Earl H, Hiller L, Vallier AL, Loi S, McAdam K, Hughes-Davies L, Rea D, Howe D, Raynes K, Higgins HB, Wilcox M, Plummer C, Mahler-Araujo B, Provenzano E, Chhabra A, Gasson S, Balmer C, Abraham JE, Caldas C, Hall P, Shinkins B, McCabe C, Hulme C, Miles D, Wardley AM, Cameron DA, Dunn JA. Six versus 12 months' adjuvant trastuzumab in patients with HER2-positive early breast cancer: the PERSEPHONE non-inferiority RCT. Health Technol Assess. 2020 Aug;24(40):1-190. doi: 10.3310/hta24400.
- Derived from this study: PubMed 31178152Earl HM, Hiller L, Vallier AL, Loi S, McAdam K, Hughes-Davies L, Harnett AN, Ah-See ML, Simcock R, Rea D, Raj S, Woodings P, Harries M, Howe D, Raynes K, Higgins HB, Wilcox M, Plummer C, Mansi J, Gounaris I, Mahler-Araujo B, Provenzano E, Chhabra A, Abraham JE, Caldas C, Hall PS, McCabe C, Hulme C, Miles D, Wardley AM, Cameron DA, Dunn JA; PERSEPHONE Steering Committee and Trial Investigators. 6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial. Lancet. 2019 Jun 29;393(10191):2599-2612. doi: 10.1016/S0140-6736(19)30650-6. Epub 2019 Jun 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Helena Earl, MBBS, PhD, FRCP principal investigator
Cambridge University Hospitals NHS Foundation Trust
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing trastuzumab and parenteral chemotherapy in people with Breast Cancer, run by Warwick Medical School at 11 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free survival. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00712140, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2011.