Ignite Creation Date:
2025-12-25 @ 1:40 AM
Ignite Modification Date:
2025-12-31 @ 11:45 AM
Study NCT ID:
NCT06523894
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-12-10
First Post:
2024-07-12
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Ablative SBRT in Elderly BC Patients
Sponsor:
University Hospital, Geneva
Organization:
Study Overview
Official Title:
EASE (brEAst Stereo Elderly): A Phase Ia/Ib Study of Stereotactic Ablative Irradiation as an Alternative to Surgery in Elderly and Comorbid Breast Cancer Subjects
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EASE
Brief Summary:
Stereotactic body radiotherapy (SBRT) is a modern radiotherapy technique, through which extremely high doses of irradiation are delivered in a very precise manner, within a few fractions. SBRT is increasingly used into clinical practice because it can provide excellent local control, comparable to surgery, in many tumor locations, such as lung, liver or bone. Efforts to develop it for BC treatment are promising, as it is safe, convenient, and effective. To date, SBRT for BC has been developed as an alternative method of partial-breast irradiation (PBI) in the pre- or post-operative setting. Therefore, the doses tested are comparable to the conventional doses used with surgery although its potential as sole local treatment for BC remains unknown. Higher SBRT doses are expected to permit obtaining an ablative effect on tumor and be suitable as an alternative to surgery, but this hypothesis has yet to be tested.
The aim of the present study is to prove the feasibility of SBRT as an ablative treatment in early breast cancer (BC). The primary objective is to find the maximum tolerated dose of SBRT that can be safely administered in inoperable patients with BC, the majority of whom are elderly or oldest old.
The overall objective is to determine whether high precision, dose- and fractionation- adapted SBRT is feasible and safe in inoperable patients with BC. The dose and fractionation-adapted SBRT regimen permits to test feasibility in different tumor sizes.
The primary objective of this study is to establish the maximum tolerated dose (MTD) that can be delivered with a single or few (up to 5) fractions of SBRT in inoperable patients with BC.
The aim of the present study is to prove the feasibility of SBRT as an ablative treatment in early breast cancer (BC). The primary objective is to find the maximum tolerated dose of SBRT that can be safely administered in inoperable patients with BC, the majority of whom are elderly or oldest old.
The overall objective is to determine whether high precision, dose- and fractionation- adapted SBRT is feasible and safe in inoperable patients with BC. The dose and fractionation-adapted SBRT regimen permits to test feasibility in different tumor sizes.
The primary objective of this study is to establish the maximum tolerated dose (MTD) that can be delivered with a single or few (up to 5) fractions of SBRT in inoperable patients with BC.
Detailed Description:
SBRT will be performed using appropriate LINACs (Truebeam®, Varian, Palo Alto, US or Cyberknife®, Accuray, Morges, Switzerland) with a volumetric arc technique (VMAT), or non-coplanal technique, depending on the treating device. The medical devices have a CE certification and will be used in the trial as stated in the CE-marked instructions for use.
The gross tumor volume (GTV), as visualized on computed tomography (CT) within clips/fiducials, when present, with a 1mm (Cyberknife®)- 3mm (TrueBeam®) isotropic margin will be treated with an adaptive fractionation, depending on its total volume within 1,3 or 5 fractions. An elective volume of 2 cm around the GTV (clinical target volume (CTV)), plus a 1mm (Cyberknife®)- 3mm (TrueBeam®) isotropic margin will be treated at constant doses by fractionation cohort. These planning target volumes (PTVs) will be cropped at 5mm to skin and chest wall. The principle of irradiating an "elective volume" around the GTV will be used in this study, as done by Vasmel et al. \[3\]. This is decided because uncertainties do exist concerning true micro- and macrometastatic extension around the tumor, as visualized in the CT and delineation of the tumor on injected CT scans is not expected to be sufficient for coverage of macro and micrometastatic disease. Breast MRI is concordant to tumor size, as evaluated in pathology, within 0.5 cm for 53% of patients \[4\]. Organs at risk will be defined according to international guidelines \[5\].
Enrolment will be performed within 1-8 weeks after discussion in the HUG Breast Cancer Multidisciplinary Tumor Board (MTB).
All patients diagnosed with BC in our Institution, presenting the aforementioned characteristics, are candidates for screening for participation in the study, and will be offered clip placement, when feasible, during diagnostic biopsy by the specialized radiologist. Screening criteria will be assessed by the radiologist and radiation oncologist at the time of diagnostic biopsy.
Pre-screened patients will be discussed at the Institutional BC MTB. Eligible patients will be considered for the study.
Treatment procedures Treatment planning: Treatment planning will be performed using appropriate TPS (Eclipse®, (Varian, Palo Alto, US) or Accuray Precision®), with relevant techniques of SBRT in order to provide dose-delivery optimizations respecting predefined criteria for target coverage and normal-tissue constraints.
Accuracy issues: Accuracy of target volume delineation and dose delivery are of outmost importance for both tumor control and toxicity avoidance, given the limited number of fractions delivered. Accuracy issues are further detailed in the protocol section 3.4.1.
Quality assurance: A quality assurance (QA) program accompanies this trial, consisting of review of treatment plans by the trial medical physicist and the coordinating investigator.
SBRT fractionation will be adapted to PTV-GTV and PTV-CTV final volumes. With increasing volumes, more fractions will be used, according to the algorithm presented below, representing the dose-adapted fractionation regimens. SBRT will be delivered with isoeffective doses: a single fraction of 21, 23, or 25 Gy on day 1 or in three fractions of 11, 13 or 14 Gy/fraction on days 1, 3 and 5 or in five fractions of 8 or 9 or 10 Gy/fraction on days 1, 3, 5, 7 and 9. Dose per adaptive regimen will be escalated every three patients if no DLT appears.
In addition, patients will undergo physical exams at each study visit and (Serious) Adverse Events ((S)AE)s will be recorded. Questionnaires will be given to patients at selected study visits to assess Quality of Life (QoL). Other study procedures include measure of vital signs, ECOG performance status and record of concomitant treatments and procedures at each study visit.
The gross tumor volume (GTV), as visualized on computed tomography (CT) within clips/fiducials, when present, with a 1mm (Cyberknife®)- 3mm (TrueBeam®) isotropic margin will be treated with an adaptive fractionation, depending on its total volume within 1,3 or 5 fractions. An elective volume of 2 cm around the GTV (clinical target volume (CTV)), plus a 1mm (Cyberknife®)- 3mm (TrueBeam®) isotropic margin will be treated at constant doses by fractionation cohort. These planning target volumes (PTVs) will be cropped at 5mm to skin and chest wall. The principle of irradiating an "elective volume" around the GTV will be used in this study, as done by Vasmel et al. \[3\]. This is decided because uncertainties do exist concerning true micro- and macrometastatic extension around the tumor, as visualized in the CT and delineation of the tumor on injected CT scans is not expected to be sufficient for coverage of macro and micrometastatic disease. Breast MRI is concordant to tumor size, as evaluated in pathology, within 0.5 cm for 53% of patients \[4\]. Organs at risk will be defined according to international guidelines \[5\].
Enrolment will be performed within 1-8 weeks after discussion in the HUG Breast Cancer Multidisciplinary Tumor Board (MTB).
All patients diagnosed with BC in our Institution, presenting the aforementioned characteristics, are candidates for screening for participation in the study, and will be offered clip placement, when feasible, during diagnostic biopsy by the specialized radiologist. Screening criteria will be assessed by the radiologist and radiation oncologist at the time of diagnostic biopsy.
Pre-screened patients will be discussed at the Institutional BC MTB. Eligible patients will be considered for the study.
Treatment procedures Treatment planning: Treatment planning will be performed using appropriate TPS (Eclipse®, (Varian, Palo Alto, US) or Accuray Precision®), with relevant techniques of SBRT in order to provide dose-delivery optimizations respecting predefined criteria for target coverage and normal-tissue constraints.
Accuracy issues: Accuracy of target volume delineation and dose delivery are of outmost importance for both tumor control and toxicity avoidance, given the limited number of fractions delivered. Accuracy issues are further detailed in the protocol section 3.4.1.
Quality assurance: A quality assurance (QA) program accompanies this trial, consisting of review of treatment plans by the trial medical physicist and the coordinating investigator.
SBRT fractionation will be adapted to PTV-GTV and PTV-CTV final volumes. With increasing volumes, more fractions will be used, according to the algorithm presented below, representing the dose-adapted fractionation regimens. SBRT will be delivered with isoeffective doses: a single fraction of 21, 23, or 25 Gy on day 1 or in three fractions of 11, 13 or 14 Gy/fraction on days 1, 3 and 5 or in five fractions of 8 or 9 or 10 Gy/fraction on days 1, 3, 5, 7 and 9. Dose per adaptive regimen will be escalated every three patients if no DLT appears.
In addition, patients will undergo physical exams at each study visit and (Serious) Adverse Events ((S)AE)s will be recorded. Questionnaires will be given to patients at selected study visits to assess Quality of Life (QoL). Other study procedures include measure of vital signs, ECOG performance status and record of concomitant treatments and procedures at each study visit.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: