Panther: A Study Comparing Biweekly and Tailored EC-T Versus Three Weekly FEC-T in Breast Cancer Patients - Full Text View

Sponsors and Collaborators:	Karolinska University Hospital Austrian Breast & Colorectal Cancer Study Group German Breast Group Finnish Breast Cancer Group
Information provided by:	Karolinska University Hospital
ClinicalTrials.gov Identifier:	NCT00798070

Purpose

This is an adjuvant, open, prospective, randomized study to compare:

A. Individually tailored and two weekly dosed epirubicin + cyclophosphamide followed by a three weeks break followed by biweekly and tailored docetaxel (dtEC→dtT) given every second week, to

B. Fixed dosed and three weekly epirubicin, cyclophosphamide and 5-fluorouracil, followed by fixed dosed and three weekly docetaxel (FEC→T).

Patients with primary node-positive or high risk lymph node negative breast cancer will be eligible for the study.

The primary objective of the phase 3 study is to compare breast cancer relapse-free survival (BCRFS) between the dtEC→dtT and FE100C→T. To detect a five-year BCRFS difference of 0.710 to 0.790 about 762 patients per arm will be needed. They will be recruited during three years and followed another two years for breast cancer events.

Secondary objectives are to compare

Distant disease-free survival (DDFS)
Event-free survival and
Overall survival
Health-related quality of life
Outcome in relation to tumour biological factors and polymorphism patterns

Tumour tissue will be obtained and stored for studies of prognostication and therapy prediction.

Condition	Intervention	Phase
Breast Cancer	Drug: Epirubicin, cyclophosphamide, docetaxel Drug: Epirubicin, cyclophosphamide, 5-fluorouracil, docetaxel	Phase III

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Cyclophosphamide Docetaxel Fluorouracil Epirubicin hydrochloride Epirubicin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Efficacy Study
Official Title:	PANTHER. A Randomized Phase 3 Study Comparing Biweekly and Tailored Epirubicin + Cyclophosphamide Followed by Biweekly Tailored Docetaxel (dtEC→dtT) Versus Three Weekly Epirubicin + Cyclophosphamide + 5-Fluorouracil Followed by Docetaxel (FEC→T) in Lymph Node Positive or High Risk Lymph Node Negative Breast Cancer Patients

Further study details as provided by Karolinska University Hospital:

Primary Outcome Measures:

Breast cancer relapse-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Distant disease-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Event-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Health-related quality of life [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Outcome in relation to tumour biological factors and polymorphism patterns [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	1524
Study Start Date:	February 2007
Estimated Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm A (dtEC→dtT): Experimental Individually tailored and two weekly dosed epirubicin + cyclophosphamide followed by a three weeks break followed by biweekly and tailored docetaxel (dtEC→dtT) given every second week	Drug: Epirubicin, cyclophosphamide, docetaxel Individually tailored and two weekly dosed epirubicin (start dose 90mg/m2) + cyclophosphamide (start dose 600mg/m2) followed by a three weeks break followed by biweekly and tailored docetaxel (start dose 75mg/m2) given every second week. If toxicity measured by CTC-NCI criteria are grade 2 or less (except haematological toxicity) it will be possible to escalate doses
Arm B (FEC→T): Active Comparator Fixed dosed and three weekly epirubicin, cyclophosphamide and 5-fluorouracil, followed by fixed dosed and three weekly docetaxel	Drug: Epirubicin, cyclophosphamide, 5-fluorouracil, docetaxel Fixed dosed and three weekly epirubicin (100mg/m2), cyclophosphamide (500mg/m2) and 5-fluorouracil (500mg/m2), followed by fixed dosed and three weekly docetaxel (100mg/m2), no dose escalations.

Arms

Assigned Interventions

Arm A (dtEC→dtT): Experimental

Individually tailored and two weekly dosed epirubicin + cyclophosphamide followed by a three weeks break followed by biweekly and tailored docetaxel (dtEC→dtT) given every second week

Drug: Epirubicin, cyclophosphamide, docetaxel

Individually tailored and two weekly dosed epirubicin (start dose 90mg/m2) + cyclophosphamide (start dose 600mg/m2) followed by a three weeks break followed by biweekly and tailored docetaxel (start dose 75mg/m2) given every second week. If toxicity measured by CTC-NCI criteria are grade 2 or less (except haematological toxicity) it will be possible to escalate doses

Arm B (FEC→T): Active Comparator

Fixed dosed and three weekly epirubicin, cyclophosphamide and 5-fluorouracil, followed by fixed dosed and three weekly docetaxel

Drug: Epirubicin, cyclophosphamide, 5-fluorouracil, docetaxel

Fixed dosed and three weekly epirubicin (100mg/m2), cyclophosphamide (500mg/m2) and 5-fluorouracil (500mg/m2), followed by fixed dosed and three weekly docetaxel (100mg/m2), no dose escalations.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histological proven invasive primary breast cancer, with at least 5 (recommended 10) removed axillary lymph nodes OR negative sentinel node biopsy performed for the node negative cohort. 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.
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.
Macroscopically and microscopically free margins after radical surgery (no cancer cells at borders of resection).
No proven distant metastases (negative chest/pulmonary X-ray, bone scintigram (when clinical signs of skeletal metastases or elevated ALP) supplemented with normal conventional X-ray of hot spots, normal liver function test and haematological function tests; when abnormal values, CT or ultrasound of the liver, patient can be included if no metastases are demonstrated.
Female age 18-65.
Ambulant patients (ECOG 1 or less).
No major cardiovascular morbidity NYHA I or II. (Appendix 3).
Written informed consent according to the local ethics committee requirements.
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).

Exclusion Criteria:

Previous neo-adjuvant treatment.
Non-radical surgery (histopathological positive margins).
Proven distant metastases.
Pregnancy or lactation.
Other serious medical condition.
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 > 5 years since diagnosis can be included.
Abnormal laboratory values precluding the possibility to safely deliver the used cytotoxic agents in the study.
Hypersensitivity to drugs formulated in polysorbate 80.
Peripheral neuropathy grade ≥2.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00798070

Contacts

Contact: Mats Hellström

+46 8 51773677

mats.hellstrom@karolinska.se

Locations

Sweden
Karolinska University Hospital, Dept of Oncology	Recruiting
Stockholm, Sweden
Contact: Jonas Bergh jonas.bergh@ki.se
Sub-Investigator: Tommy Fornander, MD, PhD
Sub-Investigator: Sam Rotstein, MD, PhD,
Sub-Investigator: Birgitta Wallberg, MD
Norrlands University Hospital	Recruiting
Umeå, Sweden
Principal Investigator: Nils-Olof Bengtsson, MD
Malmö General University Hospital	Recruiting
Malmö, Sweden
Principal Investigator: Martin Söderberg, MD
Lund University Hospital	Recruiting
Lund, Sweden
Principal Investigator: Per Malmström, MD, PhD
Sahlgrenska University Hospital	Recruiting
Göteborg, Sweden
Principal Investigator: Zakaria Einbeigi, MD, PhD
Sub-Investigator: Per Karlsson, MD, PhD
Sub-Investigator: Stig Holmberg, MD, PhD
Central Hospital	Recruiting
Sundsvall, Sweden
Principal Investigator: Lena Carlsson, MD
Örebro University Hospital	Recruiting
Örebro, Sweden
Principal Investigator: Kenneth Villman, MD
Uppsala Academic Hospital	Recruiting
Uppsala, Sweden
Principal Investigator: Henrik Lindman, MD, PhD
Central Hospital	Recruiting
Gävle, Sweden
Principal Investigator: Per Edlund, MD, PhD
Sub-Investigator: Johan Ahlgren, MD, PhD
Linköping University Hospital	Recruiting
Linköping, Sweden
Principal Investigator: Annika Malmström, MD

Sponsors and Collaborators

Karolinska University Hospital

Austrian Breast & Colorectal Cancer Study Group

German Breast Group

Finnish Breast Cancer Group

Investigators

Principal Investigator:

Jonas Bergh, MD, PhD

Karolinska University Hospital

More Information

Swedish website for the study This link exits the ClinicalTrials.gov site

Responsible Party:	Karolinska University Hospital ( Jonas Bergh, M.D., Ph.D., Professor )
Study ID Numbers:	PANTHER SBG2004-1, EudraCT 2007-002061-12, ISRCTN39017665, ABCSG25, GBG53
Study First Received:	November 24, 2008
Last Updated:	December 8, 2008
ClinicalTrials.gov Identifier:	NCT00798070
Health Authority:	Sweden: Medical Products Agency; Austria: Federal Office for Safety in Health Care; Austria: Ethikkommission; Germany: Federal Institute for Drugs and Medical Devices; Finland: National Agency for Medicines

Keywords provided by Karolinska University Hospital:

Lymph node positive or high risk lymph node negative breast
cancer

Study placed in the following topic categories:

Docetaxel
Skin Diseases
Fluorouracil
Breast Neoplasms

Cyclophosphamide
Epirubicin
Breast Diseases

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Immunosuppressive Agents

Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009