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.
18 Years
N/A
Female
Breast Cancer
Trial Information
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.
Safety.
Evaluations:
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.
During 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
toxicity.
Inclusion Criteria:
- Written informed consent
- Female patients with breast cancer confirmed by histology.
- Tumour and blood samples according to APPENDIX I available.
- Age 18 years or older. Elderly patients in condition adequate for chemotherapy.
- Localized primary breast cancer including inflammatory breast cancer suitable for
primary medical treatment and/or regional lymph node metastases including ipsilateral
supraclavicular nodes with breast cancer diagnosis confirmed by histological
examination with or without breast tumour lesions.
- Adequate bone marrow, renal, hepatic and cardiac functions and no other uncontrolled
medical or psychiatric disorders.
- ECOG performance status 0-1.
- Patients in child-bearing age with adequate contraception.
Exclusion Criteria:
- Distant metastases, including node metastases in the contralateral breast region and
in the mediastina.
- Other malignancy for the last two years except for radically treated basal or
squamous cell carcinoma of the skin or CIS of the cervix.
- HER2-amplification verified by FISH analysis.
- Pregnancy or lactation.
- Uncontrolled hypertension, heart, liver, kidney related or other medical or
psychiatric disorders.
- Recent history of thromboembolism and ongoing medication with full-dose
anticoagulants.
- Major surgery (including open biopsy), significant traumatic injury within 28 days
prior to enrollment or anticipation of the need for major surgery during study
treatment.
- Minor surgery, including insertion of an indwelling catheter, within 24 hours prior
to the first bevacizumab infusion.
- History or evidence of inherited bleeding diathesis or coagulopathy with the risk of
bleeding.
- Non-healing wound, active peptic ulcer or bone fracture.
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
within 6 months of enrollment.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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.
Outcome Time Frame:
6 weeks
Safety Issue:
No
Principal Investigator
Thomas Hatschek, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Karolinska University Hospital
Authority:
Sweden: Medical Products Agency
Study ID:
PROMIX
NCT ID:
NCT00957125
Start Date:
September 2008
Completion Date:
November 2016
Related Keywords:
- Breast Cancer
- Localized primary breast cancer
- Inflammatory breast cancer
- Breast Neoplasms
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