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

Breast Cancer Clinical Trial

— PANTHER  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00798070
• Other study ID #: PANTHER SBG2004-1
• Secondary ID: 2007-002061-12IS
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 2007
• Est. completion date: January 2022

Study information

• Verified date: September 2020
• Source: Karolinska University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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. 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

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 (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.

3. 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.

4. 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.

5. 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.

6. 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.

Description:

Are described under the heading "Outcome measures"

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2017
• Est. completion date: January 2022
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

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.

• 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).

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• dtEC?dtT
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?T
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.

Locations

Country	Name	City	State
Austria	MUG - Med. Univ.-Klinik Graz	Graz
Austria	MUI - Univ. Klinik f. Frauenheilkunde, Innsbruck	Innsbruck
Austria	LKH Leoben	Leoben
Austria	AKH Linz	Linz
Austria	KH BHS Linz	Linz
Austria	LKH Rankweil	Rankweil
Austria	LKH Salzburg / PMU	Salzburg
Austria	KH BHB St. Veit/Glan	St. Veit/Glan
Austria	Klinikum Wels - Grieskirchen GmbH	Wels
Austria	Brustzentrum Hanusch-KH	Wien
Germany	Marienhospital	Aachen
Germany	Klinikum am Bruderwald	Bamberg
Germany	Klinikum Bayreuth	Bayreuth
Germany	HELIOS Klinikum	Berlin
Germany	Klinikum Bietigheim	Bietigheim
Germany	Klinikum Sindelfingen-Böblingen	Boblingen
Germany	Johanniter Krankenhaus	Bonn
Germany	Universitätsfrauenklinik	Bonn
Germany	Krankenhaus Celle	Celle
Germany	Klinikum Deggendorf	Deggendorf
Germany	Diakonissen Krankenhaus	Dresden
Germany	Gemeinschaftspraxis	Dresden
Germany	Krankenhaus St. Joseph-Stift	Dresden
Germany	Praxis Dr. Adhami	Erkelenz
Germany	Klinikum der J. W. Goethe Universität	Frankfurt am Main
Germany	Klinikum Frankfurt Höchst GmbH	Frankfurt am Main
Germany	Onkologische Gemeinschaftspraxis	Frankfurt am Main
Germany	Kreiskrankenhaus	Freudenstadt
Germany	Klinikum Fulda	Fulda
Germany	Onkologische Schwerpunktpraxis	Goslar
Germany	Krankenhaus St. Elisabeth und St. Barbara	Halle
Germany	Universitätsfrauenklinik	Halle
Germany	Klinikum Hameln	Hameln
Germany	Henriettenstiftung	Hannover
Germany	Medizinische Hochschule	Hannover
Germany	Universität Heidelberg	Heidelberg
Germany	Klinikum Heilbronn	Heilbronn
Germany	Gemienschaftspraxis	Hildesheim
Germany	Universitätsfrauenklinik	Homburg
Germany	St. Vincentius Kliniken	Karlsruhe
Germany	Städtisches Klinikum	Karlsruhe
Germany	Elisabeth Krankenhaus	Kassel
Germany	Klinikum Kempten	Kempten
Germany	St. Elisabeth-KKH	Köln
Germany	St. Vincenz Krankenhaus	Limburg
Germany	Onkologische Tagesklinik	Lohsa
Germany	Klinikum Ludwigsburg	Ludwigsburg
Germany	Ev. Krankenhaus	Ludwigsfelde
Germany	St. Vincenz und Elisabeth-Hospital	Mainz
Germany	Universitätsfrauenklinik	Mainz
Germany	Universitätsfrauenklinik	Mannheim
Germany	Klinikum Fichtelgebirge	Marktredwitz
Germany	Onkologische Praxis	Memmingen
Germany	Gemeinschaftspraxis Münster	Münster
Germany	Praxis am Klinikum Neumarkt	Neumarkt
Germany	Onkologische Praxis	Pinneberg
Germany	Klinikum am Steinenberg	Reutlingen
Germany	Klinikum Rheinfelden	Rheinfelden
Germany	Klinikum Schwerin	Schwerin
Germany	Gesellschaft für onkologische Studien	Troisdorf
Germany	Universitätsfrauenklinik	Tübingen
Germany	Klinikum Tuttlingen	Tuttlingen
Germany	Universitätsfrauenklinik	Ulm
Germany	Klinikum Villingen-Schwenningen	Villingen
Germany	Klinikum Weiden	Weiden
Germany	Klinikum Weinheim	Weinheim
Germany	Asklepios Paulinen Klinik	Wiesbaden
Germany	St. Josefs-Hospital	Wiesbaden
Germany	Stadtkrankenhaus	Worms
Sweden	Central Hospital	Gävle
Sweden	Sahlgrenska University Hospital	Göteborg
Sweden	Central Hospital	Karlstad
Sweden	Linköping University Hospital	Linköping
Sweden	Lund University Hospital	Lund
Sweden	Malmö General University Hospital	Malmö
Sweden	Örebro University Hospital	Örebro
Sweden	Karolinska University Hospital, Dept of Oncology	Stockholm
Sweden	Central Hospital	Sundsvall
Sweden	Norrlands University Hospital	Umeå
Sweden	Uppsala Academic Hospital	Uppsala

Sponsors (4)

Lead Sponsor	Collaborator
Karolinska University Hospital	Austrian Breast & Colorectal Cancer Study Group, German Breast Group, Swedish Breast Cancer Group

Countries where clinical trial is conducted

Austria,  Germany,  Sweden, 

References & Publications (2)

Bergh J. Oral presentation, ASCO Annual Meeting 2016.

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, Hellström M, Johansson H, Anderson H, Malmström P, Gnant M, Greil R, Möbus — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	2 years
Secondary	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.	2 years
Secondary	Overall survival	Overall survival is defined as time from randomization to any death.	2 years
Secondary	Health-related quality of life and toxicity analyses according to CTC		2 years
Secondary	Outcome in relation to tumour biological factors and polymorphism patterns	Comparing arm A vs B regarding: RFS in relation to the Sorlie classes using immunohistochemical markers and/or gene expression profiling comparing A vs B arm; RFS with receptor positive disease in the comparison between the A- and B arms; RFS with high and low proliferation, respectively, in the comparison between the A- and B-arms.; 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; RFS analyzed in relation to other molecular markers in the primary cancers and SNPs signatures in normal DNA to outcome per arm; 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.	2 years
Secondary	BCRFS in arm A in relation to given dose levels	Breast cancer relapse free survival	2 years

External Links

•   Swedish website for the study