Plain English Summary
Not provided at time of registration
Trial website
Additional identifiers
EudraCT number
2007-002061-12
ClinicalTrials.gov number
NCT00798070
Protocol/serial number
SBG 2004-1/ABCSG 25/GBG53
Study information
Scientific title
A randomised phase III study comparing biweekly and tailored epirubicin plus cyclophosphamide followed by biweekly tailored docetaxel (A-arm) versus three weekly epirubicin plus cyclophosphamide, 5-fluorouracil followed by docetaxel (B-arm) in lymph node positive breast cancer patients - a continuation of the feasibility part of the SBG 2004-1 study
Acronym
The Panther Study
Study hypothesis
The aim of the study is to compare breast cancer recurrence-free survival (BCRFS; local, regional, distant breast cancer relapse or death due to breast cancer) in the tailored therapy arm compared with the fixed dose arm.
Ethics approval
Regional Ethical Board in Stockholm (Regionala etikprövningsnämnden i Stockholm), 15/01/2007, ref: 04-647/1
Study design
Phase III open prospective randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Lymph node positive breast cancer patients
Intervention
Tailored therapy arm:
Tailored epirubicin (38 - 120 mg/m^2) and cyclophosphamide (450 - 1200 mg/m^2) will be given intravenously for four courses with granulocyte colony stimulating factor (G-CSF) support. Courses should be given with a biweekly interval followed by four courses docetaxel 75 - 100 mg/m^2 with G-CSF support. The first course will start at EC Step 1, epirubicin 90 mg/m^2 and cyclophosphamide 600 mg/m^2. This is followed by four courses docetaxel 75 - 100 mg/m^2 biweekly with G-CSF support. Starting dose of docetaxel Step 0 is 75 mg/m^2.
Fixed dose arm:
Three courses of 5-fluorouracil (500 mg/m^2), epirubicin (100 mg/m^2) and cyclophosphamide 500 mg/m^2, given with a 3-week interval, will be followed by three courses of docetaxel 100 mg/m^2 given with a 3-week interval.
Intervention type
Drug
Phase
Phase III
Drug names
Epirubicin, cyclophosphamide, docetaxel, 5-fluorouracil
Primary outcome measure
Breast cancer relapse-free survival (local, regional or systemic relapse or death due to breast cancer), assessed during follow-up at 4, 8, 12, 16, 20 months and 2 years and then every 6 months until 5 years. From this point, assessment will be carried out annually until 10 years.
Secondary outcome measures
The following three outcomes will be assessed during follow-up at 4, 8, 12, 16, 20 months and 2 years and then every 6 months until 5 years. From this point, assessment will be carried out annually until 10 years:
1. Distant disease-free survival (DDFS)
2. Event-free survival
3. Overall survival
4. Health-related quality of life, assessed at baseline, 6 and 15 weeks during treatment and then at 4, 8 and 12 months during follow up
5. Outcome in relation to tumour biological factors and polymorphism patterns
Overall trial start date
01/02/2007
Overall trial end date
01/08/2011
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Current inclusion criteria as of 24/01/2011:
1. Histologically proven invasive primary breast cancer, with at least 5 (recommended 10) removed axillary lymph nodes. Interval between definitive surgery that includes axillary lymph node dissection and registration must be less than 60 days. Paraffin block from the primary tumour must be retained (not mandatory for Austrian sites). Frozen tumour tissue is strongly recommended to be stored.
2. Receptor-negative or -positive tumours with 1 or more positive axillary lymph nodes (more than 0.2 mm) OR axillary node negative breast cancers if the primary tumour is larger than 20 mm and receptor negative (Er and Pgr with no receptor content) and being Elston grade III. In Germany high-risk node-negative breast cancer patients are not eligible until labelling for docetaxel includes node-negative disease.
3. Macroscopically and microscopically radical surgery, free margins (no cancer cells at borders of resection)
4. No proven distant metastases: negative pulmonary X-ray, bone scintigram (when clinical signs of skeletal metastases or elevated alkaline phosphatase [ALP] is observed) supplemented with normal conventional X-ray of hot spots, normal liver function test and haematological function tests. Abnormal values: computed tomography (CT) or ultrasound of the liver (patient can be included if no metastases are demonstrated).
5. Female aged 18 - 65 years
6. Ambulant patients (Eastern Cooperative Oncology Group [ECOG] 1 or less)
7. No major cardiovascular morbidity: New York Heart Association (NYHA) grade I or II
8. Written informed consent according to the local ethics committee requirements
9. Patients of childbearing potential should have a negative pregnancy test within seven days of registration (in Austria, pregnancy tests have to be repeated monthly during the treatment phase)
Previous inclusion criteria:
1. Histologically proven invasive primary breast cancer, with at least 5 (recommended 10) removed axillary lymph nodes. Interval between definitive surgery that includes axillary lymph node dissection and registration must be less than 60 days. Paraffin block from the primary tumour must be retained (not mandatory for Austrian sites). Frozen tumour tissue is strongly recommended to be stored.
2. Receptor-negative or -positive tumours with 1 or more positive axillary lymph nodes (greater than 0.2 mm)
3. Macroscopically and microscopically radical surgery, free margins (no cancer cells at borders of resection)
4. No proven distant metastases: negative pulmonary X-ray, bone scintigram (when clinical signs of skeletal metastases or elevated alkaline phosphatase [ALP] is observed) supplemented with normal conventional X-ray of hot spots, normal liver function test and haematological function tests. Abnormal values: computed tomography (CT) or ultrasound of the liver (patient can be included if no metastases are demonstrated).
5. Female age 18 - 65 years
6. Ambulant patients (Eastern Cooperative Oncology Group [ECOG] 1 or less)
7. No major cardiovascular morbidity: New York Heart Association (NYHA) grade I or II
8. Written informed consent according to the local ethics committee requirements
9. Patients of childbearing potential should have a negative pregnancy test within seven days of registration (in Austria, pregnancy tests have to be repeated monthly during the treatment phase)
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
2000
Participant exclusion criteria
Current exclusion criteria as of 24/01/2011:
1. Previous neo-adjuvant treatment
2. Non-radical surgery (histopathological positive margins)
3. A primary breast cancer patient being 35 years or younger considered suitable for adjuvant chemotherapy (may be receptor negative or positive, HER-2/neu negative or positive, with or without axillary lymph node metastases)
4. Proven distant metastases
5. Pregnancy or lactation
6. Other serious medical condition
7. Previous or concurrent malignancies at other sites, except basal cell carcinoma and/or squamous cell carcinoma in situ of the skin or cervix. Patients with previous breast cancer (invasive and/or ductal carcinoma in situ) in the other breast without loco-regional (large lung volumes) radiotherapy, without objective findings for relapse, with greater than 5 years since diagnosis can be included.
8. Abnormal laboratory values precluding the possibility to safely deliver the cytotoxic agents used in the study
9. Hypersensitivity to drugs formulated in polysorbate 80
10. Peripheral neuropathy grade greater than or equal to 2
Previous exclusion criteria:
1. Previous neo-adjuvant treatment
2. Non-radical surgery (histopathological positive margins)
3. Proven distant metastases
4. Pregnancy or lactation
5. Other serious medical condition
6. Previous or concurrent malignancies at other sites, except basal cell carcinoma and/or squamous cell carcinoma in situ of the skin or cervix. Patients with previous breast cancer (invasive and/or ductal carcinoma in situ) in the other breast without loco-regional (large lung volumes) radiotherapy, without objective findings for relapse, with greater than 5 years since diagnosis can be included.
7. Abnormal laboratory values precluding the possibility to safely deliver the cytotoxic agents used in the study
8. Hypersensitivity to drugs formulated in polysorbate 80
9. Peripheral neuropathy grade greater than or equal to 2
Recruitment start date
01/02/2007
Recruitment end date
01/08/2011
Locations
Countries of recruitment
Austria, Germany, Sweden
Trial participating centre
Karolinska University Hospital
Stockholm
SE-171 76
Sweden
Sponsor information
Organisation
Karolinska University Hospital
Sponsor details
c/o Prof Jonas Bergh
Radiumhemmet
Department of Oncology
Karolinska University Hospital
Stockholm
SE-171 76
Sweden
+46 (0)8 51770000
jonas.bergh@ki.se
Sponsor type
University/education
Website
Organisation
Paracelsus University
Sponsor details
c/o Richard Greil
MD
Professor
Austrian Breast & Colorectal Cancer Study Group (ABCSG)
Department of Internal Medicine III
Salzburg
A-5020
Austria
Sponsor type
University/education
Website
Organisation
Städt. Kliniken Frankfurt-Höchst
Sponsor details
c/o Volker Möbus
MD
Professor
German Breast Group (GBG)
Frauenklinik
Gotenstrasse 6-8
Frankfurt/Höchst
D-65929
Germany
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Industry
Funder name
Swedish Cancer Society (Sweden)
Alternative name(s)
Swedish Cancer Society
Funding Body Type
private sector organisation
Funding Body Subtype
foundation
Location
Sweden
Funder name
ALF Foundation, Stockholm County Council (Sweden)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Sanofi-Aventis (Sweden)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Sanofi-Aventis (Austria)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Sanofi-Aventis (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Sanofi-Aventis (Europe)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Amgen (Sweden)
Alternative name(s)
Amgen Inc., Applied Molecular Genetics Inc.
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United States of America
Alternative name(s)
Amgen Inc., Applied Molecular Genetics Inc.
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United States of America
Alternative name(s)
Amgen Inc., Applied Molecular Genetics Inc.
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United States of America
Funder name
Amgen (Germany)
Alternative name(s)
Amgen Inc., Applied Molecular Genetics Inc.
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United States of America
Alternative name(s)
Amgen Inc., Applied Molecular Genetics Inc.
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United States of America
Alternative name(s)
Amgen Inc., Applied Molecular Genetics Inc.
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United States of America
Funder name
Amgen (Europe)
Alternative name(s)
Amgen Inc., Applied Molecular Genetics Inc.
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United States of America
Alternative name(s)
Amgen Inc., Applied Molecular Genetics Inc.
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United States of America
Alternative name(s)
Amgen Inc., Applied Molecular Genetics Inc.
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United States of America
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2016 results in: https://www.ncbi.nlm.nih.gov/pubmed/27825007