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Trastuzumab in Treating Women With HER2-Positive Early Breast Cancer

Primary Purpose

Breast Cancer

Status
Unknown status
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
trastuzumab
parenteral chemotherapy
Sponsored by
Warwick Medical School
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer, HER2-positive breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Addenbrooke's HospitalRecruiting
  • Cumberland InfirmaryRecruiting
  • Derbyshire Royal InfirmaryRecruiting
  • Eastbourne District General HospitalRecruiting
  • Luton and Dunstable HospitalRecruiting
  • Clatterbridge Centre for OncologyRecruiting
  • James Cook University HospitalRecruiting
  • Mount Vernon Cancer Centre at Mount Vernon HospitalRecruiting
  • Peterborough Hospitals TrustRecruiting
  • New Cross HospitalRecruiting
  • Aberdeen Royal InfirmaryRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm I

Arm II

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Disease-free survival

Secondary Outcome Measures

Overall survival
Cost effectiveness and quality of life
Cardiac function and analysis of predictive factors for development of cardiac damage

Full Information

First Posted
July 8, 2008
Last Updated
September 1, 2011
Sponsor
Warwick Medical School
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1. Study Identification

Unique Protocol Identification Number
NCT00712140
Brief Title
Trastuzumab in Treating Women With HER2-Positive Early Breast Cancer
Official Title
Persephone: Duration of Trastuzumab With Chemotherapy in Women With Early Stage Breast Cancer: Six Months Versus Twelve
Study Type
Interventional

2. Study Status

Record Verification Date
November 2008
Overall Recruitment Status
Unknown status
Study Start Date
October 2007 (undefined)
Primary Completion Date
October 2011 (Anticipated)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Warwick Medical School

4. Oversight

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer, HER2-positive breast cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Allocation
Randomized
Enrollment
4000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Arm II
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
trastuzumab
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
parenteral chemotherapy
Intervention Description
per the local institutional protocols either concurrently with or sequentially to trastuzumab
Primary Outcome Measure Information:
Title
Disease-free survival
Secondary Outcome Measure Information:
Title
Overall survival
Title
Cost effectiveness and quality of life
Title
Cardiac function and analysis of predictive factors for development of cardiac damage

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Helena Earl, MBBS, PhD, FRCP
Organizational Affiliation
Cambridge University Hospitals NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Addenbrooke's Hospital
City
Cambridge
State/Province
England
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Helena Earl, MBBS, PhD, FRCP
Phone
44-1223-336-800
Facility Name
Cumberland Infirmary
City
Carlisle
State/Province
England
ZIP/Postal Code
CA2 7HY
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
44-1228-523-444
Facility Name
Derbyshire Royal Infirmary
City
Derby
State/Province
England
ZIP/Postal Code
DE1 2QY
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
44-1332-347-141 ext. 2407
Facility Name
Eastbourne District General Hospital
City
Eastbourne
State/Province
England
ZIP/Postal Code
BN21 2UD
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
44-1323-417-400
Facility Name
Luton and Dunstable Hospital
City
Luton
State/Province
England
ZIP/Postal Code
LU4 0DZ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
44-845-127-0127
Facility Name
Clatterbridge Centre for Oncology
City
Merseyside
State/Province
England
ZIP/Postal Code
CH63 4JY
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
44-151-334-1155
Facility Name
James Cook University Hospital
City
Middlesbrough
State/Province
England
ZIP/Postal Code
TS4 3BW
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
44-1642-850-850
Facility Name
Mount Vernon Cancer Centre at Mount Vernon Hospital
City
Northwood
State/Province
England
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
44-1923-826-111
Facility Name
Peterborough Hospitals Trust
City
Peterborough
State/Province
England
ZIP/Postal Code
PE3 6DA
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
44-1733-874-510
Facility Name
New Cross Hospital
City
Wolverhampton
State/Province
England
ZIP/Postal Code
WV10 0QP
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
44-190-230-7999
Facility Name
Aberdeen Royal Infirmary
City
Aberdeen
State/Province
Scotland
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
44-84-5456-6000

12. IPD Sharing Statement

Citations:
PubMed Identifier
32880572
Citation
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.
Results Reference
derived
PubMed Identifier
31178152
Citation
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.
Results Reference
derived

Learn more about this trial

Trastuzumab in Treating Women With HER2-Positive Early Breast Cancer

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