Trastuzumab in Treating Women With HER2-Positive Early Breast Cancer

Breast Cancer Clinical Trial

Official title:

Persephone: Duration of Trastuzumab With Chemotherapy in Women With Early Stage Breast Cancer: Six Months Versus Twelve

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00712140
• Other study ID #: CDR0000598391
• Secondary ID: WMS-PERSEPHONEMR
• Status: Recruiting
• Phase: Phase 3
• First received: July 8, 2008
• Last updated: September 1, 2011
• Start date: October 2007

Study information

• Verified date: November 2008
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4000
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• trastuzumab
Given IV

Drug:
• parenteral chemotherapy
per the local institutional protocols either concurrently with or sequentially to trastuzumab

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Cumberland Infirmary	Carlisle	England
United Kingdom	Derbyshire Royal Infirmary	Derby	England
United Kingdom	Eastbourne District General Hospital	Eastbourne	England
United Kingdom	Luton and Dunstable Hospital	Luton	England
United Kingdom	Clatterbridge Centre for Oncology	Merseyside	England
United Kingdom	James Cook University Hospital	Middlesbrough	England
United Kingdom	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England
United Kingdom	Peterborough Hospitals Trust	Peterborough	England
United Kingdom	New Cross Hospital	Wolverhampton	England

Sponsors (1)

Lead Sponsor	Collaborator
Warwick Medical School

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival			No
Secondary	Overall survival			No
Secondary	Cost effectiveness and quality of life			No
Secondary	Cardiac function and analysis of predictive factors for development of cardiac damage			No