Uterine Cervical NeoplasmsEXITNCT03542942
Exclusion of Non-involved Uterus From the Target Volume in Locally Advanced Cervical Cancer
A study testing treatment with EXIT-target volume in people with Uterine Cervical Neoplasms, run by University Hospital, Ghent at 1 site in Belgium.
Trial summary
Both toxicity and local relapse are major concerns in the treatment of locally advanced cervical cancer. The purpose of this study is to ameliorate both by integrating modern imaging (diffusion weighted magnetic resonance imaging; DW-MRI) into the treatment planning of modern radiotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Uterine Cervical Neoplasms
- What is being tested?
- treatment with EXIT-target volume
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteBelgium
- Study dates
- 30 Mar 2016to 22 Sep 2020
- Phase
- Interventional
- 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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Biopsy proven carcinoma of the uterine cervix
- locally advanced disease (FIGO IB2 or >FIGO IIB or node positive) proven by clinical examination, 18-fluorodeoxyglucose positron emission tomography scan (18FDG PET-CT) and MRI
- no more than 2 distant metastases (other than para-aortic lymph nodes);
- WHO 0-2;
- adequate kidney function for CRT, if inadequate kidney function radiotherapy can be the sole therapeutic regimen;
- not pregnant or breastfeeding
- absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; - willing and able to sign a written informed consent.
Who cannot join
- Patients unable to undergo MRI for any reason.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Exclusion of Non-involved Uterus Form the Target Volume: an Individualized Treatment for Locally Advanced Cervical Cancer Using Modern Radiotherapy and Imaging Techniques
Both toxicity and local relapse are major concerns in the treatment of locally advanced cervical cancer. The purpose of this study is to ameliorate both by integrating modern imaging (diffusion weighted magnetic resonance imaging; DW-MRI) into the treatment planning of modern radiotherapy. We want to evaluate the safety and effect of excluding the unaffected uterus (as determined on magnetic resonance imaging) from the treatment field. Meanwhile we want to explore the possible use of apparent diffusion coefficient values (DW-MRI) as biomarker of treatment response.
Read the detailed description
In our previous research we successfully implemented Intensity Modulate Arc Therapy with concurrent administration of cisplatin 40mg/m2 weekly (IMAT-C) in the multimodality treatment of Locally Advanced Cervical Cancer (LACC) . By delivering a higher biological dose to the tumor and lowering the dose to the Organs at Risk (OARs), toxicity significantly dropped and local control improved. However, there remains room for improvement for both toxicity and response to the treatment. Macroscopic tumor rest on hysterectomy reflects the existence of chemoradiation (CRT) resistant foci and correlates with outcome. We hypothesize that both radiotherapy (RT)-related toxicity (a) as well as local response on CRT (b) can be improved by respectively:
- Reducing the dose on OARs by omitting iconographical non tumor-bearing parts of the uterus from the Clinical Target Volume (CTV).
- Performing a dose-escalation to those regions within the gross target volume (GTV) pointed out by Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) to be at risk for treatment failure.
To objectivize our hypotheses, we aim at:
- Demonstrating that omitting iconographical unaffected uterus from the treatment volume leaves no tumor behind in the non-targeted parts of the uterus, leads to lower doses to the OARs and decreases (acute) toxicity.
- Validating that a high baseline apparent diffusion coefficient (ADC) and an increase in ADC 2 weeks after start of CRT, for the whole tumor as well as for intra-tumoral regions, is prognostic for residual tumor on hysterectomy specimen and to consider the possibility for a further dose-escalation on tumors/intratumoral regions at risk for treatment failure.
Importance to the field: Both toxicity and local relapse are major concerns in the treatment of LACC. Grade ≥ 2 toxicity influences daily life of patients significantly and is present in the majority of patients treated and even with image guided BT local relapse remains the major cause of treatment failure.
- Conditions
- Uterine Cervical Neoplasms
- Being tested
- treatment with EXIT-target volume
- Keywords
- locally advanced, radiotherapy, DW-MRI, target volume
- 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.
treatment with EXIT-target volumeOther
exclusion of the unaffected part of the uterus out of the treatment field
| Study group | Role | What they receive |
|---|---|---|
| treatment with EXIT-target volume | Other | The radiotherapeutic treatment plan is based on an EXIT-target volume in which the non-involved uterus is excluded from the target volume. All other delineations are performed conform standard of care. Receives: Other: treatment with EXIT-target volume |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety: abscence of tumor in the non-involved and non-high doses irradiated part of the uterus
abscence of tumor in the non-involved (as determined on the pre-treatment MRI) and non-high doses irradiated part of the uterus in the hysterectomy specimen after CRT
Measured: within 3 months after last inclusion
Secondary outcomes (5)
dosimetry
dosimetric comparison of dose on the OARs when comparing study treatment plans compared to treatment of the whole uterus at high doses
Measured: within 3 months after last inclusion
number of participants with treatment-related adverse events as assessed by the radiotherapy oncology group toxicity criteria and CTCAEv4.0 for hematology
evaluation of acute toxicity, grade 0 (no toxicity) to grade 5 (treatment related death).
Measured: during treatment. 10 days, 1 months and 3 months after ending treatment
number of participants with treatment-related adverse events as assessed by the radiotherapy oncology group toxicity criteria and CTCAEv4.0
evaluation chronic toxicity, grade 0 (no toxicity) to grade 5 (treatment related death).
Measured: 6, 12, 18 and 24 months after treatment.
local, regional and distant control
defined as absence of disease at the primary tumor bed, the regional lymph nodes and distant sites
Measured: 1, 3, 6, 12,18 and 24 months after treatment
Correlation of high-Risk regions on IMaging (DW-MRI) with Pathology and regression pattern analysis (CRIMP).
The MRI at fixed time points will be supplemented with diffusion weighing (DW). The ultimate aim is the correlation of tumoral ADC-values of the different DW-MRI with the pathology in order to predict therapy resistance or response to CRT at an early stage or even before start.
Measured: Within 6 months after surgery of the last patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2018
- Study start30 Mar 2016
- Primary completion22 Sep 2020
- Study completion22 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Uterine Cervical NeoplasmsStudies of the same condition, open and under way.
- More trials run by University Hospital, GhentThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Ghent
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Katrien Vandecasteele, MD, PhD, Principal investigator, University Hospital, Ghent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03542942
- Sponsor's protocol ID
- B670201526181
- Acronym
- EXIT
- Status last verified
- Dec 2022
- First submitted
- 3 May 2018
- Last updated
- 19 Dec 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: IPD can be shared. Decision is made upon request.
Publications
Vandecasteele K, Tummers P, Van Bockstal M, De Visschere P, Vercauteren T, De Gersem W, Denys H, Naert E, Makar A, De Neve W. EXclusion of non-Involved uterus from the Target Volume (EXIT-trial): an individualized treatment for locally advanced cervical cancer using modern radiotherapy and imaging techniques. BMC Cancer. 2018 Sep 17;18(1):898. doi: 10.1186/s12885-018-4800-0.
PubMed 30223802
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exclusion of Non-involved Uterus Form the Target Volume: an Individualized Treatment for Locally Advanced Cervical Cancer Using Modern Radiotherapy and Imaging Techniques
- ClinicalTrials.gov ID
- NCT03542942
- Acronym / sponsor ID
- EXIT / B670201526181
- Conditions
- Uterine Cervical Neoplasms
- Keywords
- locally advanced, radiotherapy, DW-MRI, target volume
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University Hospital, GhentUniversity, hospital or other
- Study start
- 30 Mar 2016 (actual)
- Primary completion
- 22 Sep 2020 (actual)
- Study completion
- 22 Sep 2020 (actual)
- First posted
- 31 May 2018 (actual)
- 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.
Both toxicity and local relapse are major concerns in the treatment of locally advanced cervical cancer. The purpose of this study is to ameliorate both by integrating modern imaging (diffusion weighted magnetic resonance imaging; DW-MRI) into the treatment planning of modern radiotherapy. We want to evaluate the safety and effect of excluding the unaffected uterus (as determined on magnetic resonance imaging) from the treatment field. Meanwhile we want to explore the possible use of apparent diffusion coefficient values (DW-MRI) as biomarker of treatment response.
Detailed description
In our previous research we successfully implemented Intensity Modulate Arc Therapy with concurrent administration of cisplatin 40mg/m2 weekly (IMAT-C) in the multimodality treatment of Locally Advanced Cervical Cancer (LACC) . By delivering a higher biological dose to the tumor and lowering the dose to the Organs at Risk (OARs), toxicity significantly dropped and local control improved. However, there remains room for improvement for both toxicity and response to the treatment. Macroscopic tumor rest on hysterectomy reflects the existence of chemoradiation (CRT) resistant foci and correlates with outcome. We hypothesize that both radiotherapy (RT)-related toxicity (a) as well as local response on CRT (b) can be improved by respectively:
- Reducing the dose on OARs by omitting iconographical non tumor-bearing parts of the uterus from the Clinical Target Volume (CTV).
- Performing a dose-escalation to those regions within the gross target volume (GTV) pointed out by Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) to be at risk for treatment failure.
To objectivize our hypotheses, we aim at:
- Demonstrating that omitting iconographical unaffected uterus from the treatment volume leaves no tumor behind in the non-targeted parts of the uterus, leads to lower doses to the OARs and decreases (acute) toxicity.
- Validating that a high baseline apparent diffusion coefficient (ADC) and an increase in ADC 2 weeks after start of CRT, for the whole tumor as well as for intra-tumoral regions, is prognostic for residual tumor on hysterectomy specimen and to consider the possibility for a further dose-escalation on tumors/intratumoral regions at risk for treatment failure.
Importance to the field: Both toxicity and local relapse are major concerns in the treatment of LACC. Grade ≥ 2 toxicity influences daily life of patients significantly and is present in the majority of patients treated and even with image guided BT local relapse remains the major cause of treatment failure.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| treatment with EXIT-target volume | Other | Other: treatment with EXIT-target volumeThe radiotherapeutic treatment plan is based on an EXIT-target volume in which the non-involved uterus is excluded from the target volume. All other delineations are performed conform standard of care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Biopsy proven carcinoma of the uterine cervix
- locally advanced disease (FIGO IB2 or >FIGO IIB or node positive) proven by clinical examination, 18-fluorodeoxyglucose positron emission tomography scan (18FDG PET-CT) and MRI
- no more than 2 distant metastases (other than para-aortic lymph nodes);
- WHO 0-2;
- adequate kidney function for CRT, if inadequate kidney function radiotherapy can be the sole therapeutic regimen;
Key exclusion criteria (1 listed)
- Patients unable to undergo MRI for any reason.
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 |
|---|---|---|
| treatment with EXIT-target volumeexclusion of the unaffected part of the uterus out of the treatment field | Other | treatment with EXIT-target volume |
Primary outcome
safety: abscence of tumor in the non-involved and non-high doses irradiated part of the uterus
Time frame: within 3 months after last inclusion
abscence of tumor in the non-involved (as determined on the pre-treatment MRI) and non-high doses irradiated part of the uterus in the hysterectomy specimen after CRT
5 secondary outcomes
dosimetry
Time frame: within 3 months after last inclusion
number of participants with treatment-related adverse events as assessed by the radiotherapy oncology group toxicity criteria and CTCAEv4.0 for hematology
Time frame: during treatment. 10 days, 1 months and 3 months after ending treatment
number of participants with treatment-related adverse events as assessed by the radiotherapy oncology group toxicity criteria and CTCAEv4.0
Time frame: 6, 12, 18 and 24 months after treatment.
local, regional and distant control
Time frame: 1, 3, 6, 12,18 and 24 months after treatment
Correlation of high-Risk regions on IMaging (DW-MRI) with Pathology and regression pattern analysis (CRIMP).
Time frame: Within 6 months after surgery of the last patient
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2022.
- Derived from this study: PubMed 30223802Vandecasteele K, Tummers P, Van Bockstal M, De Visschere P, Vercauteren T, De Gersem W, Denys H, Naert E, Makar A, De Neve W. EXclusion of non-Involved uterus from the Target Volume (EXIT-trial): an individualized treatment for locally advanced cervical cancer using modern radiotherapy and imaging techniques. BMC Cancer. 2018 Sep 17;18(1):898. doi: 10.1186/s12885-018-4800-0.
- Individual participant dataSharing planned: Undecided. IPD can be shared. Decision is made upon request.
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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.
Katrien Vandecasteele, MD, PhD principal investigator
University Hospital, Ghent
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing treatment with EXIT-target volume in people with Uterine Cervical Neoplasms, run by University Hospital, Ghent at 1 site in Belgium.
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 7 inclusion and 1 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: finished, as of the sponsor's last update on 19 Dec 2022. 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 Belgium. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
safety: abscence of tumor in the non-involved and non-high doses irradiated part of the uterus (time frame: within 3 months after last inclusion). 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 NCT03542942, which also lists 1 linked publication.
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 19 Dec 2022.