Anthracycline-free Taxane Based Chemotherapy in Patients With HER2/Neu Negative Early Breast Cancer

NCT01049425 | Completed Phase 3 DMC

• 1 other identifier: WSG AM04
• Study Type: interventional
• Target: 3,198
• Locations: 1 country
• Sites: 1

Brief Summary

The planned trial compares an anthracycline-free taxane based regimen versus a modern third generation (anthracycline/taxane-based) regimen in HER2/neu non-over expressing tumors. The aim is to define a further anthracycline-free standard and to spare anthracycline toxicity to a patient, who will only have a modest benefit from this compound. Prior to randomization for chemotherapy for all patients with HR positive disease OncotypeDX® will be performed to identify patients who should not receive chemotherapy. Secondary objectives of this trial will be to compare overall survival and toxicity between the two chemotherapy arms, to evaluate survival in the observation arm and to perform translational research regarding prognostic and predictive factors.

Conditions

Primary Breast Cancer; Her2 Non-overexpressing

Keywords

anthracycline-free; OncotypDX; taxane; Her2 negative breast cancer

Outcome Measures

Primary Outcomes (1)

• disease-free survival in patients treated with either 6 cycles of Docetaxel / Cyclophosphamide chemotherapy or 4 cycles of EC followed by 4 cycles of Docetaxel as adjuvant treatment

  5 years

Study Arms (2)

Epirubicin and Cyclophosphamid followed by Docetaxel

ACTIVE COMPARATOR

4 cycles of EC on day one every three weeks followed by 4 cycles of Docetaxel on day one every three weeks

Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Docetaxel

Combination of Docetaxel and Cyclophosphamid

EXPERIMENTAL

intravenous infusion on day one every three weeks

Drug: Cyclophosphamide; Drug: Docetaxel

Interventions

Epirubicin DRUG

4 cycles, intravenous use, day 1 every three weeks

Epirubicin and Cyclophosphamid followed by Docetaxel

Cyclophosphamide DRUG

4 cycles, intravenous infusion, day 1 every three weeks

Epirubicin and Cyclophosphamid followed by Docetaxel

Docetaxel DRUG

4 cycles, intravenous infusion, day 1 every three weeks after completion of EC-chemotherapy

Epirubicin and Cyclophosphamid followed by Docetaxel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients, age at diagnosis 18 - 75 years
• Histological confirmed unilateral primary invasive carcinoma of the breast
• Adequate surgical treatment with complete resection of the tumor (R0) and resection of \> or = 10 axillary nodes or SLN in clinically N0 patients
• T1 - T4 (if operable, inflammatory breast cancer is excluded)
• Her-2 non-over expressing tumor confirmed by IHC/FISH
• Estrogen and/or progesterone receptor analysis performed on the primary tumor prior to randomization. Results must be known at the time of randomization
• Node positive disease or node negative disease with at least one other risk factor (tumor size \> or = 2 cm, grade \> or = 2, ER and PR negative, high uPA//PAI-1 levels)
• No evidence for distant metastasis (M0) after conventional staging
• Performance Status ECOG \< or = 1 or KI \> or = 80 %
• The patient must be accessible for treatment and follow-up
• Written informed consent for central pathology review and evaluation of Recurrence Score (HR positive) and participation in the planB trial prior to beginning specific protocol procedures
• HR positive patients:
• Patient willingness to participate in adjuvant chemotherapy planB trial if RS \> 11
• Indication for chemotherapy given provided either \> 4 involved lymph nodes or RS \> 11 in 1-3 lymph nodes or N0 disease
• Laboratory requirements (within 21 days prior to randomization):

You may not qualify if:

• HER2 over expression confirmed by IHC/FISH/CISH
• Known hypersensitivity reaction to the compounds or incorporated substances
• Known polyneuropathy \> or = grade 2
• Severe and relevant comorbidity that would interact with the application of cytotoxic agents or the participation in the study including acute cystitis and ischuria and chronic kidney disease.
• Prior malignancy with a disease-free survival of \< 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri or ipsilateral ductal carcinoma in-situ (DCISpTis of the breast)
• Non-operable breast cancer including inflammatory breast cancer
• Previous or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor
• Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry
• Male breast cancer
• Concurrent pregnancy; patients of childbearing potential must implement a highly effective (less then 1% failure rate) non-hormonal contraceptive measures during the study treatment
• Breast feeding woman
• Sequential breast cancer
• Lack of patient compliance
• Inadequate organ function including:
• Leucocytes \< 3,5 G/l

Sponsors & Collaborators

• West German Study Group: lead
• Sanofi: collaborator
• Amgen: collaborator

Study Sites (1)

Bethesda Krankenhaus

Mönchengladbach, 41061, Germany

Location

Related Publications (5)

• Sechi A, Mijnes J, Villwock S, Rose M, Steib F, Bringezu S, Berger J, Schalla C, von Serenyi S, Dietrich J, Ortiz-Bruchle N, Heij L, Bednarsch J, Gluz O, Nitz U, Harbeck N, Graeser M, Zu Eulenburg C, Mohammadian MP, Jozwiak K, Kreipe HH, Christgen M, Radner M, Jonigk D, Dahl E. The Janus Face of SPAG6: Inducing EMT in Luminal Breast Cancer Cells Amidst Widespread Expression Loss in Breast Tumours. J Cell Mol Med. 2025 Oct;29(19):e70870. doi: 10.1111/jcmm.70870.

  PMID: 41066509 DERIVED

• Kolberg-Liedtke C, Gluz O, Heinisch F, Feuerhake F, Kreipe H, Clemens M, Nuding B, Malter W, Reimer T, Wuerstlein R, Graeser M, Shak S, Nitz U, Kates R, Christgen M, Harbeck N. Association of TILs with clinical parameters, Recurrence Score(R) results, and prognosis in patients with early HER2-negative breast cancer (BC)-a translational analysis of the prospective WSG PlanB trial. Breast Cancer Res. 2020 May 14;22(1):47. doi: 10.1186/s13058-020-01283-w.

  PMID: 32408905 DERIVED

• Nitz U, Gluz O, Clemens M, Malter W, Reimer T, Nuding B, Aktas B, Stefek A, Pollmanns A, Lorenz-Salehi F, Uleer C, Krabisch P, Kuemmel S, Liedtke C, Shak S, Wuerstlein R, Christgen M, Kates RE, Kreipe HH, Harbeck N; West German Study Group PlanB Investigators. West German Study PlanB Trial: Adjuvant Four Cycles of Epirubicin and Cyclophosphamide Plus Docetaxel Versus Six Cycles of Docetaxel and Cyclophosphamide in HER2-Negative Early Breast Cancer. J Clin Oncol. 2019 Apr 1;37(10):799-808. doi: 10.1200/JCO.18.00028. Epub 2019 Feb 20.

  PMID: 30785826 DERIVED

• Nitz U, Gluz O, Christgen M, Kates RE, Clemens M, Malter W, Nuding B, Aktas B, Kuemmel S, Reimer T, Stefek A, Lorenz-Salehi F, Krabisch P, Just M, Augustin D, Liedtke C, Chao C, Shak S, Wuerstlein R, Kreipe HH, Harbeck N. Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial. Breast Cancer Res Treat. 2017 Oct;165(3):573-583. doi: 10.1007/s10549-017-4358-6. Epub 2017 Jun 29.

  PMID: 28664507 DERIVED

• Gluz O, Nitz UA, Christgen M, Kates RE, Shak S, Clemens M, Kraemer S, Aktas B, Kuemmel S, Reimer T, Kusche M, Heyl V, Lorenz-Salehi F, Just M, Hofmann D, Degenhardt T, Liedtke C, Svedman C, Wuerstlein R, Kreipe HH, Harbeck N. West German Study Group Phase III PlanB Trial: First Prospective Outcome Data for the 21-Gene Recurrence Score Assay and Concordance of Prognostic Markers by Central and Local Pathology Assessment. J Clin Oncol. 2016 Jul 10;34(20):2341-9. doi: 10.1200/JCO.2015.63.5383. Epub 2016 Feb 29.

  PMID: 26926676 DERIVED

MeSH Terms

Interventions

Epirubicin; Cyclophosphamide; Docetaxel

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

Study Officials

• Ulrike A. Nitz, Prof. Dr. med.

  Ev. Krankenhaus Bethesda Moenchengladbach

  PRINCIPAL INVESTIGATOR

• Nadia Harbeck, Prof. Dr. med.

  University Hospital Cologne

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2010
• First Posted: January 14, 2010
• Study Start: February 5, 2009
• Primary Completion: March 1, 2017
• Study Completion: May 15, 2018
• Last Updated: August 14, 2019

Record last verified: 2019-08

Locations

DE (1)