- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00920920
An International Study on Magnetic Resonance Imaging (MRI)-Guided Brachytherapy in Locally Advanced Cervical Cancer (EMBRACE)
A International Study on MRI-guided Brachytherapy in Locally Advanced Cervical Cancer
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
Study Overview
Status
Conditions
Intervention / Treatment
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:
- Small tumours
- Large tumours favourable response
- 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.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
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Vienna, Austria, 1090
- MUV
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
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).
Description
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
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
local control/morbidity
Time Frame: 5 years
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
disease free survival
Time Frame: 5 years
|
5 years
|
overall survival
Time Frame: 5 years
|
5 years
|
regional control
Time Frame: 5 years
|
5 years
|
quality of life (QoL)
Time Frame: 5 years
|
5 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Richard Pötter, Prof., M.D., Department of Radiotherapy, Medical University of Vienna
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- EMBRACE 1
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cervical Cancer
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University of California, San DiegoWithdrawnCervical Cancer | Cervical Cancer Stage | Cervical Cancer Stage IB2 | Cervical Cancer Stage IB1 | Cervical Cancer Stage I | Cervical Cancer Stage IB | Cervical Cancer Stage II | Cervical Cancer Stage IIa | Cervical Cancer, Stage IIB | Cervical Cancer, Stage III | Cervical Cancer Stage IIIB | Cervical Cancer... and other conditionsUnited States
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M.D. Anderson Cancer CenterWithdrawnStage IB3 Cervical Cancer FIGO 2018 | Stage II Cervical Cancer FIGO 2018 | Stage IIA Cervical Cancer FIGO 2018 | Stage IIA1 Cervical Cancer FIGO 2018 | Stage IIA2 Cervical Cancer FIGO 2018 | Stage IIB Cervical Cancer FIGO 2018 | Stage III Cervical Cancer FIGO 2018 | Stage IIIA Cervical Cancer FIGO... and other conditions
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Abramson Cancer Center of the University of PennsylvaniaWithdrawnCervical Cancer | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer
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National Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer | Stage IVB Cervical CancerUnited States
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Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical CancerUnited States
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Institut de Cancérologie de LorraineCompletedCervical Adenocarcinoma | Stage IB Cervical Cancer | Stage III Cervical Cancer | Stage II Cervical CancerFrance
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