A Randomized Phase III Trial Comparing Nanoparticle-based Paclitaxel With Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Patients With Early Breast Cancer (GeparSepto)
To compare the pathological complete response (pCR=ypT0 ypN0) rates of neoadjuvant treatment
of nab-paclitaxel with solvent-based paclitaxel as part of neoadjuvant treatment of operable
or locally advanced primary breast cancer
- To assess the pCR rates per arm separately for the stratified subpopulations.
- To determine the rates of ypT0/is ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0; and
- To determine the response rates of the breast tumor and axillary nodes based on
physical examination and imaging tests (sonography, mammography, or MRI) after
treatment in both arms.
- To assess clinical response rate after taxane in both groups
- To determine the breast conservation rate after each treatment.
- To assess the toxicity and compliance.
- To assess the time of onset of grade 3 neuropathy
- To assess the time of resolution of grade 3/4 neuropathy to at least grade 1
- To determine loco-regional invasive recurrence free survival (LRRFS),
distant-disease-free survival (DDFS), invasive disease-free survival (IDFS), and
overall survival (OS) in both arms and according to stratified subpopulations.
- To assess regional recurrence free survival (RRFS) in patients with initial
node-positive axilla converted to negative at surgery and treated with sentinel node
- To determine the pCR rate and local recurrence free survival (LRFS) in patients with a
clinical complete response (cCR) and a negative core biopsy before surgery.
- To examine and compare pre-specified molecular markers such as SPARC, gp60, calveoline
1 and other markers potentially differentially predicting efficacy of nab-paclitaxel
and solvent-based paclitaxel on core biopsies before, during and after chemotherapy.
Objectives of Substudies:
- To assess, characterize, and correlate circulating tumor cells and proteins with the
effect of treatment (CTC Substudy).
- To correlate Single Nucleotide Polymorphisms (SNPs) of genes with the associated
toxicity and histologically assessed treatment effect (Pharmacogenetic substudy)
- To assess ovarian function measured by amenorrhea rate in correlation with changes in
E2, FSH, LH , Anti-Müller Hormone, ultrasound-follicle count in patients aged < 45
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Pathological complete response (pCR=ypT0 ypN0) rates of neoadjuvant treatment of nab-paclitaxel with solvent-based paclitaxel as part of neoadjuvant treatment of operable or locally advanced primary breast cancer.
No microscopic evidence of residual invasive or non-invasive viable tumor cells in all resected specimens of the breast and axilla. Pathological response will be assessed considering all removed breast and lymphatic tissues from all surgeries. The primary endpoint will be summarized as pathological complete remission rate for each treatment group.
24 weeks (time window + 3 weeks)
Michael Untch, Prof MD
AGO, ASCO, DKG
Germany: Federal Institute for Drugs and Medical Devices