A Translational Trial on Molecular Markers and Functional Imaging to Predict Response of Preoperative Treatment of Breast Cancer Early (PROMIX)
Patients with localized primary breast cancer including inflammatory breast cancer suitable for primary medical treatment and/or regional lymph node metastases receive six cycles of chemotherapy with epirubicin and docetaxel. Treatment evaluations are performed after the second, fourth and sixth cycle. In case of SD/PR after the second course, bevacizumab is added to the combination for the remaining four courses.
Besides standard response evaluation clinically and by mammography and ultrasound, several functional imaging techniques including MR, CT-PET and contrast-enhanced ultrasound are investigated. Fresh tumor tissue samples from the primary tumor are collected before start, after two courses and in connection with surgery. The aim of the trial is to detect biological factors and functional imaging techniques with the ability to predict response at an early stage of treatment.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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.|
- 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. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
- Identification of tumour characteristics and treatment-related changes of tumour characteristics predictive of long-term prognosis. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Comparison between the standard evaluation procedures mammography, conventional ultrasound and clinical examination and functional imaging techniques and biological procedures with emphasis on detection of response at an early point of treatment. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
- Studies on the addition of bevacizumab with regard to further improvement of response in tumours with stable (SD) or partial response (PR) and the impact of treatment on angiogenesis and local features of the tumour environment. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
- Acute toxicity [ Time Frame: 6 weeks after last chemotherapy ] [ Designated as safety issue: Yes ]
- Late toxicity [ Time Frame: 5 years after last chemotherapy ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2008|
|Estimated Study Completion Date:||November 2016|
|Primary Completion Date:||November 2011 (Final data collection date for primary outcome measure)|
Experimental: Epirubicin Docetaxel Bevacizumab
Epirubicin and docetaxel i.v. infusion q 3 weeks for 2 cycles.
75 mg/m2 i.v. infusion, 30 min, cycle day 1, cycles 1-6.
Other Name: EpirubicinDrug: Docetaxel
75 mg/m2 i.v. infusion, 60 min, cycles day 1, cycle 1-6.
Other Name: TaxotereDrug: Bevacizumab
15 mg/kg, i.v. infusion, 90 min, cycle day 1, cycles 3-6 if PR or SD after cycle 2.
Other Name: Avastin
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.
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 toxicity.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00957125
|Sahlgrenska University Hospital|
|Lund University Hospital|
|Malmö General University Hospital|
|Karolinska University Hospital, Dept of Oncology|
|Stockholm, Sweden, SE-17176|
|Principal Investigator:||Thomas Hatschek, MD, PhD||Karolinska University Hospital|