An International Study on Magnetic Resonance Imaging (MRI)-Guided Brachytherapy in Locally Advanced Cervical Cancer (EMBRACE)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by Medical University of Vienna.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Aarhus University Hospital
UMC Utrecht
Leiden University Medical Center
Katholieke Universiteit Leuven
Mount Vernon Hospital
Institute of Oncology Ljubljana
Information provided by:
Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT00920920
First received: June 12, 2009
Last updated: June 15, 2009
Last verified: June 2009
  Purpose

Background:

The standard treatment of locally advanced cervical cancer is radio-chemotherapy including external beam radiotherapy (EBRT), brachytherapy (BT) and concomitant chemotherapy with weekly Cisplatin. While image based conformal EBRT is routinely used, prescription and reporting of BT is still based on specific dose points defined in 2D. Thus, for several decades the BT dose has most often been prescribed and reported to the Manchester point A defined according to different traditions.

Recently, a working group from GEC-ESTRO has published recommendations on contouring of tumour target and organs at risk (OAR) as well as on dose volume parameters to be reported for image guided BT in definitive radiotherapy for locally advanced cervical cancer. These recommendations are mainly derived from retrospective single institution experience with MRI based intracavitary BT. The major advantage of this technique is the possibility to conform the dose given by BT with regard to both volume (3D) and time (4D). Thus, by repetitive imaging performed before each BT implant it is possible adapt the dose given by BT to the anatomy of each individual patient taking into account not only the position of OAR but also the tumour regression which often is obtained by preceding EBRT and chemotherapy. Based on the experience collected so far, the image based BT approach is expected to have a major impact on the clinical outcome with a concomitant decrease in the rates of both local failure and morbidity.

Aims:

  • To introduce MRI based 3D-4D BT in locally advanced cervical cancer in a multicenter setting within the frame of a prospective observational study.
  • To establish a bench-mark for clinical outcome with image based BT in a large patient population with respect to local control, survival, morbidity and QoL
  • To establish a reference material with regard to image based DVH parameters according to the guidelines from the GEC ESTRO working group.
  • To correlate image based DVH parameters for CTV and for OAR with outcome
  • To develop prognostic and predictive statistical models for clinical outcome including volumetric, dosimetric, clinical and biological risk factors
  • To establish radiobiological parameter estimates that will allow a precise risk estimation in individual patients and aid in the development of new treatment protocols

Condition Intervention
Cervical Cancer
Radiation: 3D MRI-guided Brachytherapy

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A International Study on MRI-Guided Brachytherapy in Locally Advanced Cervical Cancer

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • local control/morbidity [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • regional control [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • disease free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • quality of life (QoL) [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 600
Study Start Date: July 2008
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Radiation: 3D MRI-guided Brachytherapy
    MRI-based 3D-4D brachytherapy in locally advanced cervical cancer
Detailed Description:

A prospective observational multicenter study will be performed in patients with locally advanced cervical cancer considered to be potentially curable by definitive radio-(chemo) therapy. The patients will be divided and analyzed in three strata according to risk of recurrence:

  1. Small tumours
  2. Large tumours favourable response
  3. Large tumours with unfavourable response to the initial radio-(chemo) therapy.

A clinical local failure has to be validated by MRI and topographically correlated to the MRI based BT targets (HR CTV and IR-CTV) and the dose volume parameters of the treatment plan. It has to be classified as "inside", "at the edge", "outside".

Major events with regard to morbidity have to be reported using 3D imaging information integrating e.g. clinical examination, endoscopy and MRI. The location of organ damage (i.e. fistula) has to be identified in 3D and a correlation to the dose volume parameters for the affected region should be investigated.

Specific Aims

  • To assess prospectively outcome for disease (local control, survival), for morbidity and for QoL life applying appropriate clinical, imaging and QoL protocols.
  • To test that there are three groups representing different risks of recurrence: small tumours; large tumours with favourable response; large tumours with unfavourable response to initial radio-(chemo)therapy.
  • To correlate local control (survival) and dose volume parameters for GTV and CTV for the overall cohort and for the 3 different risk groups and to establish hazard ratios and dose effect curves for the primary tumour.
  • To correlate outcome data and dose volume parameters for the different OAR (rectum, sigmoid, bladder) and to establish hazard ratios and dose effect curves for OAR.
  • To correlate QoL outcome to morbidity outcome.
  • To quantify the change in DVH parameters obtained by image guided dose optimization of BT in the individual patient.
  • To compare volumetric data on GTV and CTV at diagnosis and during treatment and relate them to dose volume parameters within the 3 different risk groups of the overall patient cohort.
  • To evaluate the indicators for quality assessment throughout the whole study period in order to define systematic and random variations for the different indicators (e.g. contouring, applicator reconstruction, dose volume assessment).
  • To validate from clinical outcome data the radiobiological equivalence calculations used for assessing dose and volume parameters in gynaecological radiotherapy.
  • To test if the GYN GEC ESTRO recommendations for BT in cervical cancer are feasible in a multi-centre setting.
  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients to be included:

Patients with newly biopsy proven squamous carcinoma, adenocarcinoma or adeno-squamous carcinoma of the uterine cervix, FIGO stage IB, IIA, IIB, IIIA, IIIB and IVA in whom definitive radiotherapy with curative intent is planned are qualified for the study. Patients with para-aortic metastatic nodes (stage IVB) to the level of L2 are also eligible but patients with further dissemination are not.

Staging should as a minimal include gynaecological examination, MRI of the pelvis, abdominal CT or MRI and chest radiography. Further investigations are applied if necessary (e.g. cystoscopy, rectoscopy) or normally done according to institutional practice (e.g. PET-CT).

Criteria

Inclusion Criteria:

  • Cancer of the uterine cervix considered suitable for curative treatment with definitive radio-(chemo)therapy including MRI guided BT
  • Positive biopsy showing squamous-cell carcinoma, adenocarcinoma or adeno-squamous cell carcinoma of the uterine cervix.
  • Staging according to FIGO and TNM guidelines
  • MRI of pelvis at diagnosis is performed
  • MRI, CT or PET-CT of the retroperitoneal space and abdomen at diagnosis is performed
  • MRI with the applicator in place at the time of (first) BT will be performed
  • Para-aortic metastatic nodes below L1-L2 are allowed
  • Patient informed consent

Exclusion Criteria:

  • Other primary malignancies except carcinoma in situ of the cervix and basal cell carcinoma of the skin
  • Metastatic disease beyond para-aortic region (L1-L2)
  • Previous pelvic or abdominal radiotherapy
  • Previous total or partial hysterectomy
  • Combination of preoperative radiotherapy with surgery
  • Patients receiving BT only
  • Patients receiving EBRT only
  • Patients receiving neoadjuvant chemotherapy
  • Contra indications to MRI
  • Contra indications to BT
  • Active infection or severe medical condition endangering treatment delivery
  • Pregnant, lactating or childbearing potential without adequate contraception
  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: NCT00920920

Contacts
Contact: Richard Pötter, MD +43 1 40 400 ext 2692 richard.poetter@akhwien.at
Contact: Jacob Lindegaard, MD, PhD +45 8949 2577 jlind@as.aaa.dk

Locations
Austria
MUV Recruiting
Vienna, Austria, 1090
Contact: Richard Pötter, MD    0043140400 ext 2692    richard.poetter@akhwien.at   
Contact: Elena Fidarova, MD    0043140400 ext 2664    elena.fidarova@akhwien.at   
Sponsors and Collaborators
Medical University of Vienna
Aarhus University Hospital
UMC Utrecht
Leiden University Medical Center
Katholieke Universiteit Leuven
Mount Vernon Hospital
Institute of Oncology Ljubljana
Investigators
Principal Investigator: Richard Pötter, Prof., M.D. Department of Radiotherapy, Medical University of Vienna
  More Information

Additional Information:
No publications provided

Responsible Party: Univ. Prof. Dr. Richard Pötter, Department of Radiotherapy, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT00920920     History of Changes
Other Study ID Numbers: EMBRACE 1
Study First Received: June 12, 2009
Last Updated: June 15, 2009
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Vienna:
3D-4D MRI-based Brachytherapy
Cervical Cancer
Multicenter Clinical Study
Locally advanced cervical cancer

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms

ClinicalTrials.gov processed this record on October 21, 2014