Exclusion of Non-involved Uterus From the Target Volume in Locally Advanced Cervical Cancer (EXIT)

• ClinicalTrials.gov Identifier: NCT03542942
• Recruitment Status: Unknown
• First Posted: May 31, 2018
• Last Update Posted: May 31, 2018
• Sponsor: University Hospital, Ghent
• Information provided by (Responsible Party): University Hospital, Ghent

Study Description

Brief 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. 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.

Condition or disease	Intervention/treatment	Phase
Uterine Cervical Neoplasms	Other: treatment with EXIT-target volume	Not Applicable

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:

1. Reducing the dose on OARs by omitting iconographical non tumor-bearing parts of the uterus from the Clinical Target Volume (CTV).
2. 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:

1. 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.
2. 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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 30, 2016
• Estimated Primary Completion Date: December 30, 2018
• Estimated Study Completion Date: December 30, 2020

Arms and Interventions

Arm	Intervention/treatment
treatment with EXIT-target volume; 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.	Other: treatment with EXIT-target volume; exclusion of the unaffected part of the uterus out of the treatment field

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. dosimetry [ Time Frame: within 3 months after last inclusion ]
   dosimetric comparison of dose on the OARs when comparing study treatment plans compared to treatment of the whole uterus at high doses
2. 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 ]
   evaluation of acute toxicity, grade 0 (no toxicity) to grade 5 (treatment related death).
3. 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. ]
   evaluation chronic toxicity, grade 0 (no toxicity) to grade 5 (treatment related death).
4. local, regional and distant control [ Time Frame: 1, 3, 6, 12,18 and 24 months after treatment ]
   defined as absence of disease at the primary tumor bed, the regional lymph nodes and distant sites
5. 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 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Patients unable to undergo MRI for any reason.

Contacts and Locations

Contacts

Contact: Katrien Vandecasteele, MD, PhD; 00329325974; katrien.vandecasteele@uzgent.be

Contact: Wilfried De Neve, MD, PhD; 003293323016; wilfried.deneve@uzgent.be

Locations

Belgium

Radiotherapy Department Ghent University Hospital; Recruiting

Gent, Belgium, 9000

Contact: Katrien Vandecasteele, MD, PhD 003293325974 katrien.vandecasteele@uzgent.be

Contact: Wilfried De Neve, MD, PhD 003293323016 wilfried.deneve@uzgent.be

Sponsors and Collaborators

University Hospital, Ghent

Investigators

• Principal Investigator: Katrien Vandecasteele, MD, PhD; University Hospital, Ghent

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University Hospital, Ghent
• ClinicalTrials.gov Identifier: NCT03542942
• Other Study ID Numbers: B670201526181
• First Posted: May 31, 2018
• Last Update Posted: May 31, 2018
• Last Verified: May 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: IPD can be shared. Decision is made upon request.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Ghent:

locally advanced; radiotherapy; DW-MRI; target volume

Additional relevant MeSH terms:

Uterine Cervical Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases