ABCSG 25/PANTHER Details

A randomized phase-III-study; Comparing biweekly and tailored epirubicin and cyclophosphamide followed by biweekly tailored docetaxel (dtEC, dtT) (A-arm) vs. three weekly epirubicin and cyclophosphamide, 5-fluorouracil followed by docetaxel (FEC, T) (B-arm) in lymph node positive or high risk lymph node negative breast cancer patients – a continuation of the feasibility part of the SBG 2004-1


Contact ABCSG-Trial office

E-mail: info@abcsg.at
Phone: +43 1 408 92 30
Fax: +43 1 409 09 90

Design

ABCSG-25-Design
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Primary objectives:

Compare breast cancer recurrence-free survival (BCRFS) (local-, regional-, distant breast cancer relapse or death due to breast cancer), in the tailored therapy arm (dtEC x 4®dtT x 4, A-arm) compared with the fixed dosed arm (FEC x 3®T x 3, B-arm).

Secondary objectives:

  1. Compare distant disease free survival (DDFS) (distant metastases or death due to breast cancer)
  2. Compare event-free survival (breast cancer relapse, contra-lateral breast cancer, other malignancies, or any cause of death
  3. Compare overall survival (OS)
  4. Health-related quality of life
  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 aanlyzed 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

Inclusion criteria:

  1. 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.
  2. 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
  3. 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)
  4. Macroscopically and microscopically free margins after radical surgery (no cancer cells at borders of resection)
  5. 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
  6. Female age 18-65
  7. Ambulant patients (ECOG 1 or less)
  8. No major cardiovascular morbidity NYHA I or II
  9. Written informed consent according to the local ethics committee requirements
  10. 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:

  1. Previous neo-adjuvant treatment
  2. Non-radical surgery (histopathological positive margins)
  3. Proven distant metastases
  4. Pregnancy or lactation
  5. Other serious medical condition
  6. 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
  7. Abnormal laboratory values precluding the possibility to safely deliver the used cytotoxic agents in the study
  8. Hypersensitivity to drugs formulated in polysorbate 80
  9. Peripheral neuropathy grade ≥2