A Translational Trial on Molecular Markers and Functional Imaging to Predict Response of Preoperative Treatment of Breast Cancer Early (PROMIX)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Thomas Hatschek, Karolinska University Hospital
ClinicalTrials.gov Identifier:
NCT00957125
First received: August 10, 2009
Last updated: February 27, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Epirubicin
Drug: Docetaxel
Drug: Bevacizumab
Phase 2

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Karolinska University Hospital:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 150
Study Start Date: September 2008
Estimated Study Completion Date: November 2016
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Epirubicin
75 mg/m2 i.v. infusion, 30 min, cycle day 1, cycles 1-6.
Other Name: Epirubicin
Drug: Docetaxel
75 mg/m2 i.v. infusion, 60 min, cycles day 1, cycle 1-6.
Other Name: Taxotere
Drug: 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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00957125

Locations
Sweden
Sahlgrenska University Hospital
Göteborg, Sweden
Lund University Hospital
Lund, Sweden
Malmö General University Hospital
Malmö, Sweden
Karolinska University Hospital, Dept of Oncology
Stockholm, Sweden, SE-17176
County Hospital
Sundsvall, Sweden
Akademic Hospital
Uppsala, Sweden
Sponsors and Collaborators
Thomas Hatschek
Investigators
Principal Investigator: Thomas Hatschek, MD, PhD Karolinska University Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Thomas Hatschek, MD, PhD, Karolinska University Hospital
ClinicalTrials.gov Identifier: NCT00957125     History of Changes
Other Study ID Numbers: PROMIX, 2007-005858-23
Study First Received: August 10, 2009
Last Updated: February 27, 2012
Health Authority: Sweden: Medical Products Agency

Keywords provided by Karolinska University Hospital:
Localized primary breast cancer
Inflammatory breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Bevacizumab
Docetaxel
Epirubicin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Tubulin Modulators

ClinicalTrials.gov processed this record on October 20, 2014