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Breast CancerPhase 3PANTHERNCT00798070

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

A Phase 3 study testing dtEC→dtT and FEC→T in people with Breast Cancer, run by Karolinska University Hospital at 80 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
dtEC→dtT and FEC→T
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2,017 participants
Where
80 sitesin 3 countries
Study dates
Feb 2007to Jan 2028
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 10Show fewer
  • 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).

Who cannot join

  • 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.
Show all 9Show fewer
  • 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.

Trial locations and contacts

80 sites in 3 countries.

80 sites in 3 countries

Germany59 sites

  • Marienhospital

    Aachen

  • Klinikum am Bruderwald

    Bamberg

  • Klinikum Bayreuth

    Bayreuth

  • HELIOS Klinikum

    Berlin

  • Klinikum Bietigheim

    Bietigheim

  • Klinikum Sindelfingen-Böblingen

    Böblingen

  • Johanniter Krankenhaus

    Bonn

  • Universitätsfrauenklinik

    Bonn

  • Krankenhaus Celle

    Celle

  • St. Elisabeth-KKH

    Cologne

  • Klinikum Deggendorf

    Deggendorf

  • Diakonissen Krankenhaus

    Dresden

  • Gemeinschaftspraxis

    Dresden

  • Krankenhaus St. Joseph-Stift

    Dresden

  • Praxis Dr. Adhami

    Erkelenz

  • Klinikum der J. W. Goethe Universität

    Frankfurt am Main

  • Klinikum Frankfurt Höchst GmbH

    Frankfurt am Main

  • Onkologische Gemeinschaftspraxis

    Frankfurt am Main

  • Kreiskrankenhaus

    Freudenstadt

  • Klinikum Fulda

    Fulda

  • Onkologische Schwerpunktpraxis

    Goslar

  • Krankenhaus St. Elisabeth und St. Barbara

    Halle

  • Universitätsfrauenklinik

    Halle

  • Klinikum Hameln

    Hamelin

  • Henriettenstiftung

    Hanover

  • Medizinische Hochschule

    Hanover

  • Universität Heidelberg

    Heidelberg

  • Klinikum Heilbronn

    Heilbronn

  • Gemienschaftspraxis

    Hildesheim

  • Universitätsfrauenklinik

    Homburg

  • St. Vincentius Kliniken

    Karlsruhe

  • Städtisches Klinikum

    Karlsruhe

  • Elisabeth Krankenhaus

    Kassel

  • Klinikum Kempten

    Kempten

  • St. Vincenz Krankenhaus

    Limburg

  • Onkologische Tagesklinik

    Lohsa

  • Klinikum Ludwigsburg

    Ludwigsburg

  • Ev. Krankenhaus

    Ludwigsfelde

  • St. Vincenz und Elisabeth-Hospital

    Mainz

  • Universitätsfrauenklinik

    Mainz

  • Universitätsfrauenklinik

    Mannheim

  • Klinikum Fichtelgebirge

    Marktredwitz

  • Onkologische Praxis

    Memmingen

  • Gemeinschaftspraxis Münster

    Münster

  • Praxis am Klinikum Neumarkt

    Neumarkt

  • Onkologische Praxis

    Pinneberg

  • Klinikum am Steinenberg

    Reutlingen

  • Klinikum Rheinfelden

    Rheinfelden

  • Klinikum Schwerin

    Schwerin

  • Gesellschaft für onkologische Studien

    Troisdorf

  • Universitätsfrauenklinik

    Tübingen

  • Klinikum Tuttlingen

    Tuttlingen

  • Universitätsfrauenklinik

    Ulm

  • Klinikum Villingen-Schwenningen

    Villingen

  • Klinikum Weiden

    Weiden

  • Klinikum Weinheim

    Weinheim

  • Asklepios Paulinen Klinik

    Wiesbaden

  • St. Josefs-Hospital

    Wiesbaden

  • Stadtkrankenhaus

    Worms

Other trials in Germany

Sweden11 sites

  • Central Hospital

    Gävle

  • Sahlgrenska University Hospital

    Gothenburg

  • Central Hospital

    Karlstad

  • Linköping University Hospital

    Linköping

  • Lund University Hospital

    Lund

  • Malmö General University Hospital

    Malmö

  • Örebro University Hospital

    Örebro

  • Karolinska University Hospital, Dept of Oncology

    Stockholm

  • Central Hospital

    Sundsvall

  • Norrlands University Hospital

    Umeå

  • Uppsala Academic Hospital

    Uppsala

Other trials in Sweden

Austria10 sites

  • MUG - Med. Univ.-Klinik Graz

    Graz

  • MUI - Univ. Klinik f. Frauenheilkunde, Innsbruck

    Innsbruck

  • LKH Leoben

    Leoben

  • AKH Linz

    Linz

  • KH BHS Linz

    Linz

  • LKH Rankweil

    Rankweil

  • KH BHB St. Veit/Glan

    Saint Veit/Glan

  • LKH Salzburg / PMU

    Salzburg

  • Brustzentrum Hanusch-KH

    Vienna

  • Klinikum Wels - Grieskirchen GmbH

    Wels

Other trials in Austria

About this study

Official title: A Randomised Phase 3 Study Comparing Biweekly and Tailored Epirubicin + Cyclophosphamide Followed by Biweekly Tailored Docetaxel Versus Three Weekly Epirubicin + Cyclophosphamide + 5-fluorouracil Followed by Docetaxel in Lymph Node Positive or High Risk Lymph Node Negative Breast Cancer Patients

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

  1. 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
  2. Fixed dosed and three weekly epirubicin, cyclophosphamide and 5-fluorouracil, followed by fixed dosed and three weekly docetaxel (FEC→T).
Read more

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. Distant disease-free survival (DDFS)
  2. Event-free survival and
  3. Overall survival
  4. Health-related quality of life and toxicity analyses according to CTC
  5. Outcome in relation to tumour biological factors and polymorphism patterns
  6. RFS in relation to the Sorlie classes using immunohistochemical markers and/or gene expression profiling comparing A vs B arm
  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. 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. 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. 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. RFS analyzed in relation to tumour associated lymphocytes and Y-box binding protein in the comparison between the A- and B-arms.

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

Last patient randomized was September 2011.

Read the detailed description

Are described under the heading "Outcome measures"

Conditions
Breast Cancer
Being tested
dtEC→dtT, FEC→T
Keywords
Lymph node positive or high risk lymph node negative breast, cancer
Medical subject headings
Breast Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • dtEC→dtTDrug

    Also called Epirubicin, Cyclophosphamide, Taxotere

    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

  • FEC→TDrug

    Also called Epirubicin, Cyclophosphamide, Fluorouracil, Taxotere

    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.

Study groups in NCT00798070
Study groupRoleWhat they receive
Arm A: dtEC→dtTExperimentalIndividually 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
Receives: Drug: dtEC→dtT
Arm B: FEC→TActive comparatorFixed dosed and three weekly epirubicin, cyclophosphamide and 5-fluorouracil, followed by fixed dosed and three weekly docetaxel
Receives: Drug: FEC→T

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 2 years

Secondary outcomes (6)

  1. Distant disease-free survival

    Distant disease free survival is defined as time from randomization to the first of distant metastases or death due to breast cancer.

    Measured: 2 years

  2. Event-free survival

    Event-free survival is defined as time from randomization to the first of the events breast cancer recurrence (any type), contra-lateral breast cancer, other malignancy or any cause of death.

    Measured: 2 years

  3. Overall survival

    Overall survival is defined as time from randomization to any death.

    Measured: 2 years

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

    Measured: 2 years

  5. Outcome in relation to tumour biological factors and polymorphism patterns

    Comparing arm A vs B regarding:

    1. RFS in relation to the Sorlie classes using immunohistochemical markers and/or gene expression profiling comparing A vs B arm;
    2. RFS with receptor positive disease in the comparison between the A- and B arms;
    3. RFS with high and low proliferation, respectively, in the comparison between the A- and B-arms.;
    4. RFS in relation to HER-2/neu status in the primary cancers in the comparison between the A- and B-arms and analyzed whether trastuzumab was given in sequence or concurrently;
    5. RFS analyzed in relation to other molecular markers in the primary cancers and SNPs signatures in normal DNA to outcome per arm;
    6. RFS analyzed in relation to tumour associated lymphocytes and Y-box binding protein in the comparison between the A- and B-arms.

    Description of a to e are more detailed in the protocol, shortened here due to space limitation.

    Measured: 2 years

  6. BCRFS in arm A in relation to given dose levels

    Breast cancer relapse free survival

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Nov 2008 (estimated)
  2. Study startFeb 2007
  3. Primary completionApr 2016
  4. Study completionJan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
2,017 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00798070
Sponsor's protocol ID
PANTHER SBG2004-1
Other IDs
2007-002061-12, ISRCTN39017665, ABCSG25, GBG53
Acronym
PANTHER
Status last verified
Nov 2024
First submitted
24 Nov 2008
Last updated
18 Dec 2024
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: Oral presentation at ASCO 4 June 2016 (completed).

Publications

  • 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.

    PubMed 30739743

  • 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.

    PubMed 39703564

  • 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.

    PubMed 39018515

  • 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.

    PubMed 34799582

  • 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.

    PubMed 32232698

  • 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.

    PubMed 31851385

  • 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.

    PubMed 31583943

  • 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.

    PubMed 30357310

  • 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.

    PubMed 29190004

  • 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.

    PubMed 27825007

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

  • 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.

    PubMed 21174610

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing dtEC→dtT and FEC→T in people with Breast Cancer, run by Karolinska University Hospital at 80 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 80 sites in Germany, Sweden, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Breast cancer relapse-free survival (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00798070, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2024.

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