Trastuzumab in Treating Women With HER2-Positive Early Breast Cancer
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.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Forventet)
Fase
- Fase 3
Kontakter og lokationer
Studiesteder
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England
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Cambridge, England, Det Forenede Kongerige, CB2 2QQ
- Rekruttering
- Addenbrooke's Hospital
-
Kontakt:
- Helena Earl, MBBS, PhD, FRCP
- Telefonnummer: 44-1223-336-800
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Carlisle, England, Det Forenede Kongerige, CA2 7HY
- Rekruttering
- Cumberland Infirmary
-
Kontakt:
- Contact Person
- Telefonnummer: 44-1228-523-444
-
Derby, England, Det Forenede Kongerige, DE1 2QY
- Rekruttering
- Derbyshire Royal Infirmary
-
Kontakt:
- Contact Person
- Telefonnummer: 44-1332-347-141 ext. 2407
-
Eastbourne, England, Det Forenede Kongerige, BN21 2UD
- Rekruttering
- Eastbourne District General Hospital
-
Kontakt:
- Contact Person
- Telefonnummer: 44-1323-417-400
-
Luton, England, Det Forenede Kongerige, LU4 0DZ
- Rekruttering
- Luton and Dunstable Hospital
-
Kontakt:
- Contact Person
- Telefonnummer: 44-845-127-0127
-
Merseyside, England, Det Forenede Kongerige, CH63 4JY
- Rekruttering
- Clatterbridge Centre for Oncology
-
Kontakt:
- Contact Person
- Telefonnummer: 44-151-334-1155
-
Middlesbrough, England, Det Forenede Kongerige, TS4 3BW
- Rekruttering
- James Cook University Hospital
-
Kontakt:
- Contact Person
- Telefonnummer: 44-1642-850-850
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Northwood, England, Det Forenede Kongerige, HA6 2RN
- Rekruttering
- Mount Vernon Cancer Centre at Mount Vernon Hospital
-
Kontakt:
- Contact Person
- Telefonnummer: 44-1923-826-111
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Peterborough, England, Det Forenede Kongerige, PE3 6DA
- Rekruttering
- Peterborough Hospitals Trust
-
Kontakt:
- Contact Person
- Telefonnummer: 44-1733-874-510
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Wolverhampton, England, Det Forenede Kongerige, WV10 0QP
- Rekruttering
- New Cross Hospital
-
Kontakt:
- Contact Person
- Telefonnummer: 44-190-230-7999
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-
Scotland
-
Aberdeen, Scotland, Det Forenede Kongerige, AB25 2ZN
- Rekruttering
- Aberdeen Royal Infirmary
-
Kontakt:
- Contact Person
- Telefonnummer: 44-84-5456-6000
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Aktiv komparator: 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.
All patients also receive standard chemotherapy regimens as per local institutional protocols either concurrently with or sequentially to trastuzumab.
|
Givet IV
per the local institutional protocols either concurrently with or sequentially to trastuzumab
|
|
Eksperimentel: 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.
|
Givet IV
per the local institutional protocols either concurrently with or sequentially to trastuzumab
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
|---|
|
Sygdomsfri overlevelse
|
Sekundære resultatmål
Resultatmål |
|---|
|
Samlet overlevelse
|
|
Cost effectiveness and quality of life
|
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Cardiac function and analysis of predictive factors for development of cardiac damage
|
Samarbejdspartnere og efterforskere
Sponsor
Publikationer og nyttige links
Generelle publikationer
- 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.
- Earl 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.
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Forventet)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- CDR0000598391
- WMS-PERSEPHONE
- MREC-PERSEPHONE
- EUDRACT: 2006-007018-39
- ISRCTN 52968807
- MREC 07/MRE08/35
- EU-20858
- CRUK-BRD/07/137
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