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

NCT00798070 | Active Not Recruiting Phase 3 DMC

• 5 other identifiers: PANTHER SBG2004-12007-002061-12ISRCTN39017665ABCSG25GBG53
• Study Type: interventional
• Target: 2,017
• Locations: 3 countries
• Sites: 80

Brief Summary

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 1000 patients per arm will be needed. They will be recruited during four years and followed another two years for breast cancer events. Secondary objectives are to compare

1. 1.Distant disease-free survival (DDFS)
2. 2.Event-free survival and
3. 3.Overall survival
4. 4.Health-related quality of life and toxicity analyses according to CTC
5. 5.Outcome in relation to tumour biological factors and polymorphism patterns
6. 6.RFS in relation to the Sorlie classes using immunohistochemical markers and/or gene expression profiling comparing A vs B arm
7. 7.RFS with receptor positive disease (analyzed in the local laboratories as described in the CRFs and also analyzed as continuous variables) in the comparison between the A- and B- arms.
8. 8.RFS with high and low proliferation, respectively, (analyzed in the local laboratories as described in the CRFs and also analyzed as a continuous variable, or centrally analyzed), in the comparison between the A- and B-arms.
9. 9.RFS in relation to HER-2/neu status (analyzed in the local laboratories as described in the CRFs) in the primary cancers in the comparison between the A- and B-arms and analyzed whether trastuzumab was given in sequence or concurrently.
10. 10.RFS analyzed in relation to other molecular markers (e.g. gene expression profiling/ sequencing) in the primary cancers and SNPs signatures in normal DNA (related to toxicities for EC/FEC and docetaxel components, respectively, and given dose levels and outcome in relation to these factors and in relation QoL) to outcome per arm.
11. 11.RFS analyzed in relation to tumour associated lymphocytes and Y-box binding protein in the comparison between the A- and B-arms.

Conditions

Breast Cancer

Keywords

Lymph node positive or high risk lymph node negative breast; cancer

Outcome Measures

Primary Outcomes (1)

• Breast cancer relapse-free survival

  Breast cancer recurrence free survival is defined as time from randomization to the first of the events; local-, regional- or distant breast cancer recurrence or death due to breast cancer or last date of follow-up if no event has occurred. This was defined already in the phase 2 protocol (1 Sept 2004).

  2 years

Secondary Outcomes (6)

• Distant disease-free survival

  2 years

• Event-free survival

  2 years

• Overall survival

  2 years

• Health-related quality of life and toxicity analyses according to CTC

  2 years

• Outcome in relation to tumour biological factors and polymorphism patterns

  2 years

Study Arms (2)

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: dtEC→dtT

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: FEC→T

Interventions

dtEC→dtT DRUG

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

Also known as: Epirubicin, Cyclophosphamide, Taxotere

Arm A: dtEC→dtT

FEC→T DRUG

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.

Also known as: Epirubicin, Cyclophosphamide, Fluorouracil, Taxotere

Arm B: FEC→T

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Karolinska University Hospital: lead
• Swedish Breast Cancer Group: collaborator
• Austrian Breast & Colorectal Cancer Study Group: collaborator
• GBG Forschungs GmbH: collaborator

Study Sites (80)

MUG - Med. Univ.-Klinik Graz

Graz, Austria

Location

MUI - Univ. Klinik f. Frauenheilkunde, Innsbruck

Innsbruck, Austria

Location

LKH Leoben

Leoben, Austria

Location

AKH Linz

Linz, Austria

Location

KH BHS Linz

Linz, Austria

Location

LKH Rankweil

Rankweil, Austria

Location

KH BHB St. Veit/Glan

Saint Veit/Glan, Austria

Location

LKH Salzburg / PMU

Salzburg, Austria

Location

Brustzentrum Hanusch-KH

Vienna, Austria

Location

Klinikum Wels - Grieskirchen GmbH

Wels, Austria

Location

Marienhospital

Aachen, Germany

Location

Klinikum am Bruderwald

Bamberg, Germany

Location

Klinikum Bayreuth

Bayreuth, Germany

Location

HELIOS Klinikum

Berlin, Germany

Location

Klinikum Bietigheim

Bietigheim, Germany

Location

Johanniter Krankenhaus

Bonn, Germany

Location

Universitätsfrauenklinik

Bonn, Germany

Location

Klinikum Sindelfingen-Böblingen

Böblingen, Germany

Location

Krankenhaus Celle

Celle, Germany

Location

St. Elisabeth-KKH

Cologne, Germany

Location

Klinikum Deggendorf

Deggendorf, Germany

Location

Diakonissen Krankenhaus

Dresden, Germany

Location

Gemeinschaftspraxis

Dresden, Germany

Location

Krankenhaus St. Joseph-Stift

Dresden, Germany

Location

Praxis Dr. Adhami

Erkelenz, Germany

Location

Klinikum der J. W. Goethe Universität

Frankfurt am Main, Germany

Location

Klinikum Frankfurt Höchst GmbH

Frankfurt am Main, Germany

Location

Onkologische Gemeinschaftspraxis

Frankfurt am Main, Germany

Location

Kreiskrankenhaus

Freudenstadt, Germany

Location

Klinikum Fulda

Fulda, Germany

Location

Onkologische Schwerpunktpraxis

Goslar, Germany

Location

Krankenhaus St. Elisabeth und St. Barbara

Halle, Germany

Location

Universitätsfrauenklinik

Halle, Germany

Location

Klinikum Hameln

Hamelin, Germany

Location

Henriettenstiftung

Hanover, Germany

Location

Medizinische Hochschule

Hanover, Germany

Location

Universität Heidelberg

Heidelberg, Germany

Location

Klinikum Heilbronn

Heilbronn, Germany

Location

Gemienschaftspraxis

Hildesheim, Germany

Location

Universitätsfrauenklinik

Homburg, Germany

Location

St. Vincentius Kliniken

Karlsruhe, Germany

Location

Städtisches Klinikum

Karlsruhe, Germany

Location

Elisabeth Krankenhaus

Kassel, Germany

Location

Klinikum Kempten

Kempten, Germany

Location

St. Vincenz Krankenhaus

Limburg, Germany

Location

Onkologische Tagesklinik

Lohsa, Germany

Location

Klinikum Ludwigsburg

Ludwigsburg, Germany

Location

Ev. Krankenhaus

Ludwigsfelde, Germany

Location

St. Vincenz und Elisabeth-Hospital

Mainz, Germany

Location

Universitätsfrauenklinik

Mainz, Germany

Location

Universitätsfrauenklinik

Mannheim, Germany

Location

Klinikum Fichtelgebirge

Marktredwitz, Germany

Location

Onkologische Praxis

Memmingen, Germany

Location

Gemeinschaftspraxis Münster

Münster, Germany

Location

Praxis am Klinikum Neumarkt

Neumarkt, Germany

Location

Onkologische Praxis

Pinneberg, Germany

Location

Klinikum am Steinenberg

Reutlingen, Germany

Location

Klinikum Rheinfelden

Rheinfelden, Germany

Location

Klinikum Schwerin

Schwerin, Germany

Location

Gesellschaft für onkologische Studien

Troisdorf, Germany

Location

Klinikum Tuttlingen

Tuttlingen, Germany

Location

Universitätsfrauenklinik

Tübingen, Germany

Location

Universitätsfrauenklinik

Ulm, Germany

Location

Klinikum Villingen-Schwenningen

Villingen, Germany

Location

Klinikum Weiden

Weiden, Germany

Location

Klinikum Weinheim

Weinheim, Germany

Location

Asklepios Paulinen Klinik

Wiesbaden, Germany

Location

St. Josefs-Hospital

Wiesbaden, Germany

Location

Stadtkrankenhaus

Worms, Germany

Location

Central Hospital

Gävle, Sweden

Location

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Central Hospital

Karlstad, Sweden

Location

Linköping University Hospital

Linköping, Sweden

Location

Lund University Hospital

Lund, Sweden

Location

Malmö General University Hospital

Malmo, Sweden

Location

Örebro University Hospital

Örebro, Sweden

Location

Karolinska University Hospital, Dept of Oncology

Stockholm, Sweden

Location

Central Hospital

Sundsvall, Sweden

Location

Norrlands University Hospital

Umeå, Sweden

Location

Uppsala Academic Hospital

Uppsala, Sweden

Location

Related Publications (12)

• Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials. Lancet. 2019 Apr 6;393(10179):1440-1452. doi: 10.1016/S0140-6736(18)33137-4. Epub 2019 Feb 8.

  PMID: 30739743 BACKGROUND

• Matikas A, Papakonstantinou A, Loibl S, Steger GG, Untch M, Johansson H, Tsiknakis N, Hellstrom M, Greil R, Mobus V, Gnant M, Bergh J, Foukakis T. Benefit from dose-dense adjuvant chemotherapy for breast cancer: subgroup analyses from the randomised phase 3 PANTHER trial. Lancet Reg Health Eur. 2024 Dec 3;49:101162. doi: 10.1016/j.lanepe.2024.101162. eCollection 2025 Feb.

  PMID: 39703564 RESULT

• Matikas A, Mobus V, Greil R, Andersson A, Steger GG, Untch M, Fornander T, Malmstrom P, Schmatloch S, Johansson H, Hellstrom M, Brandberg Y, Gnant M, Loibl S, Foukakis T, Bergh J; SweBCG, ABCSG and GBG. Tailored Dose-Dense Versus Standard Adjuvant Chemotherapy for High-Risk Early Breast Cancer: End-of-Study Results of the Randomized PANTHER Trial. J Clin Oncol. 2024 Sep 10;42(26):3077-3082. doi: 10.1200/JCO.24.00178. Epub 2024 Jul 17.

  PMID: 39018515 RESULT

• Zerdes I, Simonetti M, Matikas A, Harbers L, Acs B, Boyaci C, Zhang N, Salgkamis D, Agartz S, Moreno-Ruiz P, Bai Y, Rimm DL, Hartman J, Mezheyeuski A, Bergh J, Crosetto N, Foukakis T. Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study. NPJ Breast Cancer. 2021 Nov 19;7(1):144. doi: 10.1038/s41523-021-00352-3.

  PMID: 34799582 RESULT

• Brandberg Y, Johansson H, Hellstrom M, Gnant M, Mobus V, Greil R, Foukakis T, Bergh J; Swedish Breast Cancer Group, the Austrian Breast, Colorectal Cancer Study Group, the German Breast Cancer Group. Long-term (up to 16 months) health-related quality of life after adjuvant tailored dose-dense chemotherapy vs. standard three-weekly chemotherapy in women with high-risk early breast cancer. Breast Cancer Res Treat. 2020 May;181(1):87-96. doi: 10.1007/s10549-020-05602-9. Epub 2020 Mar 31.

  PMID: 32232698 RESULT

• Papakonstantinou A, Matikas A, Bengtsson NO, Malmstrom P, Hedayati E, Steger G, Untch M, Hubbert L, Johansson H, Hellstrom M, Gnant M, Loibl S, Greil R, Moebus V, Foukakis T, Bergh J. Efficacy and safety of tailored and dose-dense adjuvant chemotherapy and trastuzumab for resected HER2-positive breast cancer: Results from the phase 3 PANTHER trial. Cancer. 2020 Mar 15;126(6):1175-1182. doi: 10.1002/cncr.32653. Epub 2019 Dec 18.

  PMID: 31851385 RESULT

• Papakonstantinou A, Hedayati E, Hellstrom M, Johansson H, Gnant M, Steger G, Greil R, Untch M, Moebus V, Loibl S, Foukakis T, Bergh J, Matikas A. Neutropenic complications in the PANTHER phase III study of adjuvant tailored dose-dense chemotherapy in early breast cancer. Acta Oncol. 2020 Jan;59(1):75-81. doi: 10.1080/0284186X.2019.1670353. Epub 2019 Oct 4.

  PMID: 31583943 RESULT

• Matikas A, Foukakis T, Moebus V, Greil R, Bengtsson NO, Steger GG, Untch M, Johansson H, Hellstrom M, Malmstrom P, Gnant M, Loibl S, Bergh J. Dose tailoring of adjuvant chemotherapy for breast cancer based on hematologic toxicities: further results from the prospective PANTHER study with focus on obese patients. Ann Oncol. 2019 Jan 1;30(1):109-114. doi: 10.1093/annonc/mdy475.

  PMID: 30357310 RESULT

• Matikas A, Margolin S, Hellstrom M, Johansson H, Bengtsson NO, Karlsson L, Edlund P, Karlsson P, Lidbrink E, Linderholm B, Lindman H, Malmstrom P, Villman K, Foukakis T, Bergh J. Long-term safety and survival outcomes from the Scandinavian Breast Group 2004-1 randomized phase II trial of tailored dose-dense adjuvant chemotherapy for early breast cancer. Breast Cancer Res Treat. 2018 Apr;168(2):349-355. doi: 10.1007/s10549-017-4599-4. Epub 2017 Nov 30.

  PMID: 29190004 RESULT

• Foukakis T, von Minckwitz G, Bengtsson NO, Brandberg Y, Wallberg B, Fornander T, Mlineritsch B, Schmatloch S, Singer CF, Steger G, Egle D, Karlsson E, Carlsson L, Loibl S, Untch M, Hellstrom M, Johansson H, Anderson H, Malmstrom P, Gnant M, Greil R, Mobus V, Bergh J; Swedish Breast Cancer Group (SweBCG), the German Breast Group (GBG), and the Austrian Breast & Colorectal Cancer Study Group (ABCSG). Effect of Tailored Dose-Dense Chemotherapy vs Standard 3-Weekly Adjuvant Chemotherapy on Recurrence-Free Survival Among Women With High-Risk Early Breast Cancer: A Randomized Clinical Trial. JAMA. 2016 Nov 8;316(18):1888-1896. doi: 10.1001/jama.2016.15865.

  PMID: 27825007 RESULT

• Bergh J. Oral presentation, ASCO Annual Meeting 2016.

  RESULT

• Margolin S, Bengtsson NO, Carlsson L, Edlund P, Hellstrom M, Karlsson P, Lidbrink E, Linderholm B, Lindman H, Malmstrom P, Pettersson Skold D, Soderberg M, Villman K, Bergh J; Scandinavian Breast Group Study SBG 2004-1. A randomised feasibility/phase II study (SBG 2004-1) with dose-dense/tailored epirubicin, cyclophoshamide (EC) followed by docetaxel (T) or fixed dosed dose-dense EC/T versus T, doxorubicin and C (TAC) in node-positive breast cancer. Acta Oncol. 2011 Jan;50(1):35-41. doi: 10.3109/0284186X.2010.535847.

  PMID: 21174610 RESULT

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms

Interventions

Epirubicin; Cyclophosphamide; Docetaxel; Fluorouracil

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jonas Bergh, MD, PhD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: November 24, 2008
• First Posted: November 25, 2008
• Study Start: February 1, 2007
• Primary Completion: April 1, 2016
• Study Completion (Estimated): January 1, 2028
• Last Updated: December 18, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

AU (10); SE (11); DE (59)