PROMIX - Preoperative Treatment of Breast Cancer With a Combination of Epirubicin, Docetaxel and Bevacizumab. A Translational Trial on Molecular Markers and Functional Imaging to Predict Response Early. A Phase 2 Study.
Primary endpoints: Objective response (OR) characterized by conventional radiological and
functional imaging procedures and biological tumour markers at an early point of treatment
with epirubicin + docetaxel and effects of addition of bevacizumab as reflected by these
procedures. Early functional and biological changes signalling pathological complete
response (pCR). Secondary endpoints: Secondary endpoints: Morphological and biological
changes of tumours exposed for cytotoxic and targeted treatment. Disease-free survival.
Before start of treatment:
Tumour staging: Bone scan, chest X-ray and liver ultrasound or CT scan of chest and abdomen
within four weeks before start of treatment. Physical examination, conventional radiology
(ultrasound and mammography including pre-treatment localization with carbon suspension) and
functional imaging procedure (MRI or PET-CT or Contrast-Enhanced Ultrasound (CEUS) or
Scintigraphy with 99m-Tc-HMPAO (Ceretec)) within two weeks before start of treatment.
Blood samples (SNP, metabolomics, M-30 assay, TK/XPA-210 assay, angiogenesis markers,
TIMP-1, tissue factor) and tumour biopsies (transcriptomics, proteomics, IHC-stroma, AMOT)
are collected within two weeks before start of treatment.
Physical examination before start of each treatment. Imaging procedures: Mammography,
ultrasound (compulsory) one week (5-9 days) after cycles 2, 4 and 6. MRI, PET-CT,
Contrast-Enhanced Ultrasound (CEUS) applied according to availability at the participating
sites, one week (5-9 days) after cycles 2 and 4.
Tumour markers: Blood samples (proteomics, metabolomics, M-30 assay, TK/XPA-210 assay,
angiogenesis markers, TIMP-1, tissue factor) are collected 48 hours after cycles 1 thru 4.
Tumour tissue (transcriptomics, proteomics, IHC-stroma, AMOT) is taken charge of by biopsy
one week (5-9 days) after cycle 2 and from the tumour specimen in connection with surgery.
Totally, 150-200 patients with measurable/evaluable primary breast cancer are planned for
inclusion within a period of two years time. For each imaging method, approximately 40-50
patients will be included. The study is designed to find early predictors of response by
testing a set-up of several different molecular and imaging tools. In addition, for each
method changes of patterns occurring during treatment will be compared to baseline findings
and, in the case of functional imaging, standard imaging procedures.
All patients will be followed for five years after operation with regard to outcome and
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Evaluation of the sensitivity and of defined diagnostic and biological procedures to detect response/non-response to neoadjuvant treatment at an early point among patients with breast cancer.
Thomas Hatschek, MD, PhD
Karolinska University Hospital
Sweden: Medical Products Agency