Cervical CancerEMBRACENCT00920920
An International Study on Magnetic Resonance Imaging (MRI)-Guided Brachytherapy in Locally Advanced Cervical Cancer
An observational study of Cervical Cancer, run by Medical University of Vienna at 1 site in Austria.
Trial summary
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. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Cervical Cancer
- What is being tested?
- 3D MRI-guided Brachytherapy
- Type of treatment
- Surgery or procedure
- How many people
- 1,416 participants
- Where
- 1 siteAustria
- Study dates
- Jul 2008to Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
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).
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read more
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
Read the 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.
- Conditions
- Cervical Cancer
- Being tested
- 3D MRI-guided Brachytherapy
- Keywords
- 3D-4D MRI-based Brachytherapy, Cervical Cancer, Multicenter Clinical Study, Locally advanced cervical cancer
- Medical subject headings
- Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3D MRI-guided BrachytherapyRadiation
MRI-based 3D-4D brachytherapy in locally advanced cervical cancer
What is being measured
The primary outcome is the main question the study is designed to answer.
local control/morbidity
Measured: 5 years
Secondary outcomes (4)
regional control
Measured: 5 years
disease free survival
Measured: 5 years
overall survival
Measured: 5 years
quality of life (QoL)
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2009 (estimated)
- Study startJul 2008
- Primary completionDec 2021 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cervical CancerStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,416 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital, UMC Utrecht, Leiden University Medical Center, KU Leuven, Mount Vernon Hospital, Institute of Oncology Ljubljana, ARTI Institute for Radiation Oncology Arnhem, Maastricht University Medical Center, Gustave Roussy, Cancer Campus, Grand Paris, Tata Memorial Hospital, Kaposvár University, Medical College of Wisconsin, Leeds Cancer Centre at St. James's University Hospital, St. Olavs Hospital, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), British Columbia Cancer Agency, Cambridge University Hospitals NHS Foundation Trust, Post Graduate Institute of Medical Education and Research, Chandigarh, University of Alberta, University of Iowa, Kuopio University Hospital, Oslo University Hospital, Hospital of Navarra
- Responsible party
- Principal investigator, Richard Pötter, Medical University of Vienna
- Investigators
- Richard Pötter, Prof., M.D., Principal investigator, Department of Radiotherapy, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00920920
- Sponsor's protocol ID
- EMBRACE 1
- Acronym
- EMBRACE
- Status last verified
- Mar 2021
- First submitted
- 12 Jun 2009
- Last updated
- 25 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Schmid MP, Lindegaard JC, Mahantshetty U, Tanderup K, Jurgenliemk-Schulz I, Haie-Meder C, Fokdal LU, Sturdza A, Hoskin P, Segedin B, Bruheim K, Huang F, Rai B, Cooper R, van der Steen-Banasik E, Van Limbergen E, Pieters BR, Petric P, Ramazanova D, Ristl R, Kannan S, Hawaldar R, Ecker S, Kirchheiner K, Tan LT, Nout R, Nesvacil N, de Leeuw A, Potter R, Kirisits C; EMBRACE Collaborative Group. Risk Factors for Local Failure Following Chemoradiation and Magnetic Resonance Image-Guided Brachytherapy in Locally Advanced Cervical Cancer: Results From the EMBRACE-I Study. J Clin Oncol. 2023 Apr 1;41(10):1933-1942. doi: 10.1200/JCO.22.01096. Epub 2023 Jan 4.
PubMed 36599120Potter R, Tanderup K, Schmid MP, Jurgenliemk-Schulz I, Haie-Meder C, Fokdal LU, Sturdza AE, Hoskin P, Mahantshetty U, Segedin B, Bruheim K, Huang F, Rai B, Cooper R, van der Steen-Banasik E, Van Limbergen E, Pieters BR, Tan LT, Nout RA, De Leeuw AAC, Ristl R, Petric P, Nesvacil N, Kirchheiner K, Kirisits C, Lindegaard JC; EMBRACE Collaborative Group. MRI-guided adaptive brachytherapy in locally advanced cervical cancer (EMBRACE-I): a multicentre prospective cohort study. Lancet Oncol. 2021 Apr;22(4):538-547. doi: 10.1016/S1470-2045(20)30753-1.
PubMed 33794207
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A International Study on MRI-guided Brachytherapy in Locally Advanced Cervical Cancer
- ClinicalTrials.gov ID
- NCT00920920
- Acronym / sponsor ID
- EMBRACE / EMBRACE 1
- Conditions
- Cervical Cancer
- Keywords
- 3D-4D MRI-based Brachytherapy, Cervical Cancer, Multicenter Clinical Study, Locally advanced cervical cancer
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,416 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Collaborators
- Aarhus University Hospital, UMC Utrecht, Leiden University Medical Center, KU Leuven, Mount Vernon Hospital, Institute of Oncology Ljubljana, ARTI Institute for Radiation Oncology Arnhem, Maastricht University Medical Center, Gustave Roussy, Cancer Campus, Grand Paris, Tata Memorial Hospital, Kaposvár University, Medical College of Wisconsin, Leeds Cancer Centre at St. James's University Hospital, St. Olavs Hospital, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), British Columbia Cancer Agency, Cambridge University Hospitals NHS Foundation Trust, Post Graduate Institute of Medical Education and Research, Chandigarh, University of Alberta, University of Iowa, Kuopio University Hospital, Oslo University Hospital, Hospital of Navarra
- Study start
- Jul 2008
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 15 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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).
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 3D MRI-guided BrachytherapyMRI-based 3D-4D brachytherapy in locally advanced cervical cancer | Radiation | – |
Primary outcome
local control/morbidity
Time frame: 5 years
4 secondary outcomes
regional control
Time frame: 5 years
disease free survival
Time frame: 5 years
overall survival
Time frame: 5 years
quality of life (QoL)
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2021.
- Derived from this study: PubMed 36599120Schmid MP, Lindegaard JC, Mahantshetty U, Tanderup K, Jurgenliemk-Schulz I, Haie-Meder C, Fokdal LU, Sturdza A, Hoskin P, Segedin B, Bruheim K, Huang F, Rai B, Cooper R, van der Steen-Banasik E, Van Limbergen E, Pieters BR, Petric P, Ramazanova D, Ristl R, Kannan S, Hawaldar R, Ecker S, Kirchheiner K, Tan LT, Nout R, Nesvacil N, de Leeuw A, Potter R, Kirisits C; EMBRACE Collaborative Group. Risk Factors for Local Failure Following Chemoradiation and Magnetic Resonance Image-Guided Brachytherapy in Locally Advanced Cervical Cancer: Results From the EMBRACE-I Study. J Clin Oncol. 2023 Apr 1;41(10):1933-1942. doi: 10.1200/JCO.22.01096. Epub 2023 Jan 4.
- Derived from this study: PubMed 33794207Potter R, Tanderup K, Schmid MP, Jurgenliemk-Schulz I, Haie-Meder C, Fokdal LU, Sturdza AE, Hoskin P, Mahantshetty U, Segedin B, Bruheim K, Huang F, Rai B, Cooper R, van der Steen-Banasik E, Van Limbergen E, Pieters BR, Tan LT, Nout RA, De Leeuw AAC, Ristl R, Petric P, Nesvacil N, Kirchheiner K, Kirisits C, Lindegaard JC; EMBRACE Collaborative Group. MRI-guided adaptive brachytherapy in locally advanced cervical cancer (EMBRACE-I): a multicentre prospective cohort study. Lancet Oncol. 2021 Apr;22(4):538-547. doi: 10.1016/S1470-2045(20)30753-1.
- Official homepage of the EMBRACE studyLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Pötter, Prof., M.D. principal investigator
Department of Radiotherapy, Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cervical Cancer, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
local control/morbidity (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00920920, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2021.