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.
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 151
- 试验地点
- 6
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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-
- •Patients in child-bearing age with adequate contraception.
排除标准
- •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.
研究组 & 干预措施
Epirubicin Docetaxel Bevacizumab
Epirubicin and docetaxel i.v. infusion q 3 weeks for 2 cycles.
- If complete response this treatment continues for 4 cycles, totally 6 cycles.
- If partial response or stable disease, epirubicin and docetaxel and bevacizumab i.v. infusion q 3 weeks for 4 cycles.
- If progressive disease after the first 2 cycles individualized treatment.
干预措施: Epirubicin (Drug)
Epirubicin Docetaxel Bevacizumab
Epirubicin and docetaxel i.v. infusion q 3 weeks for 2 cycles.
- If complete response this treatment continues for 4 cycles, totally 6 cycles.
- If partial response or stable disease, epirubicin and docetaxel and bevacizumab i.v. infusion q 3 weeks for 4 cycles.
- If progressive disease after the first 2 cycles individualized treatment.
干预措施: Docetaxel (Drug)
Epirubicin Docetaxel Bevacizumab
Epirubicin and docetaxel i.v. infusion q 3 weeks for 2 cycles.
- If complete response this treatment continues for 4 cycles, totally 6 cycles.
- If partial response or stable disease, epirubicin and docetaxel and bevacizumab i.v. infusion q 3 weeks for 4 cycles.
- If progressive disease after the first 2 cycles individualized treatment.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
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.
时间窗: 6 weeks
次要结局
- Acute toxicity(6 weeks after last chemotherapy)
- Late toxicity(5 years after last chemotherapy)
- 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.(6 weeks)
- Identification of tumour characteristics and treatment-related changes of tumour characteristics predictive of long-term prognosis.(5 years)
- 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.(6 weeks)
研究者
Thomas Hatschek
MD, PhD
Karolinska University Hospital