Soft Tissue Sarcoma Adult, Soft Tissue Sarcoma (Excluding GIST), Soft Tissue Sarcoma of the Limb, Soft Tissue Sarcoma of the Trunk and Extremities
Conditions
Keywords
Sarcoma, Trunk, Limb, Radiotherapy, Neoadjuvant
Brief summary
This trial aims to assess the long-term efficacy of moderately hypofractionated neoadjuvant radiotherapy for soft tissue sarcoma in the limbs or trunk wall. The primary outcome is local disease control, assessed by the cumulative incidence of progression/recurrence. After informed consent has been obtained and eligibility criteria have been checked, a baseline assessment will be performed followed by the experimental treatment: intensity-modulated radiotherapy with a moderately hypofractionated regimen consisting in 15 fractions of 2.7 Gy administered over 3 weeks. a follow-up assessment will be performed 3 to 4 weeks after the last radiotherapy session. Tumor resection will be performed 4 to 8 weeks after the radiotherapy. Patients will then be followed up until the end of the study; planned 5 years after the last inclusion. Radiotherapy will be evaluated in terms of safety and efficacy.
Detailed description
The NEORASARC clinical trial aims to assess the long-term efficacy of moderately hypofractionated neoadjuvant radiotherapy for soft tissue sarcoma in the limbs or trunk wall. After informed consent has been obtained and eligibility criteria have been checked, a baseline assessment will be performed 8 weeks prior to the start of experimental treatment. This baseline assessment will consist in of a clinical examination, an MRI scan, and the completion of the MSTS and QLQ-C30 questionnaires. After a blood sample has been taken for translational research, the patient will receive the experimental treatment : intensity-modulated radiotherapy delivered in a moderately hypofractionated scheme consisting in 15 fractions of 2.7 Gy over 3 weeks. The total prescribed dose will be 40.5 Gy. 3 to 4 weeks after the last radiotherapy session, patients will undergo an MRI scan. Tumor resection will be performed 4 to 8 weeks after the radiotherapy. A blood sample will be taken prior to this surgery for translational research. Patients will then be followed up every 4 months for the first 2 years, every 6 months for 3 years and then annually until the end of the study. At each follow up, a clinical examination, an MRI scan and the completion of the MSTS and QLQ-C30/F17 questionnaires will be performed. The study is planned to end 5 years after the last inclusion. The security and efficacy of the experimental treatment will be assessed. The main analysis will focus on the cumulative incidence of local progressive disease or recurrence at the two-year follow-up. It is expected that 90% of patients are free of local progression or recurrence at two years in this population and with different radiotherapy regimen. A proportion of patients free from local progression or recurrence at two years of 90% or less will be considered insufficient (p0 = 90%). The alternative hypothesis under consideration is p1 = 95%.
Interventions
RADIATIONModerately hypofractionated neoadjuvant radiotherapy
Intensity-modulated radiotherapy with a moderately hypofractionated scheme consisting of 15 fractions of 2.7 Gy administered over 3 weeks.
Sponsors
Centre Oscar Lambret
Canther, Lille
Centre de traitement des données du Cancéropôle Nord-Ouest, Centre F. BACLESSE, Caen, France
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient aged ≥ 18 years ; * Localised sarcoma of a limb, the root of a limb, or the trunk wall ; * Histologically confirmed diagnosis of soft tissue sarcoma regardless of the grade ; * Diagnosis biopsy performed at Centre Oscar Lambret, with specimen available for translational research ; * Indication of neoadjuvant radiotherapy according to the multidisciplinary consultation meeting ; * Tumor considered operable with a curative intent and conservative intent according to the multidisciplinary consultation meeting ; * Affiliation to the French National Social Security System ; * Informed and signed consent
Exclusion criteria
* Metastatic disease (including local lymph node diffusion) ; * Visceral or retroperitoneal sarcoma ; * Tumor considered inoperable even after radiotherapy, according to the multidisciplinary consultation meeting ; * Indication of neoadjuvant or adjuvant chemotherapy ; * Ewing tumor of soft tissue, desmoid tumor, embryonal or alveolar rhabdomyosarcoma ; * Pregnant or breastfeeding women ; * Patients under protective measures ; * Patient refusal.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local control of the disease at the two-year follow-up | From enrollment to the two-year follow-up | Local control of the disease will be assessed by cumulative incidence of local progression / recurrence. The main primary outcome analysis will focus on this incidence at the two-year follow-up. The cumulative incidence of local progression / recurrence will be estimated by considering the time between the start of radiotherapy and the date of local progression / recurrence. For patients who are free of local progression / recurrence, this time will be censored at the last follow-up. Death without prior local progression / recurrence and metastatic progression / recurrence without prior local progression / recurrence will be considered competing events. Pre-operative tumor assessment will be performed according to the RECIST 1.1 criteria. For the main analysis, a progressive disease according to RECIST 1.1 criteria during or at the end of radiotherapy will not be considered as an event if the patient remains eligible for surgical resection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Control of the disease at the two-year follow-up | From enrollment to the end of study, planned 5 years after the last enrollment | Recurrence-free survival will be defined as the time between the start of radiotherapy and the date of progression / recurrence (local or metastatic) or death, whatever the cause. Observations of patients who were alive and free of progression / recurrence at the last follow up will be censored at that date. The three components of recurrence-free survival will be described: cumulative incidence of local progression / recurrence as described in the primary outcome, cumulative incidence of metastatic recurrence (time between the start of radiotherapy and the date of metastatic progression / recurrence), and cumulative incidence of death without prior progression / recurrence (time between the start of radiotherapy and the date of death without prior progression / recurrence). |
| Local control of the disease at the two-year follow-up - sensitivity analysis | From enrollment to the two-year follow-up | Local control of the disease will be assessed as described in the main primary outcome but: * For the first sensitivity analysis, metastatic progression / recurrence prior to local progression will not be considered a competing event. * For the second sensitivity analysis, a progressive disease according to RECIST 1.1 criteria during or at the end of radiotherapy will be considered as an event even if the patient remains eligible for surgical resection. |
| Overall survival | From enrollment to the end of study, planned 5 years after the last enrollment | Overall survival will be defined as the time between the start of radiotherapy and the date of death, regardless of the cause. Patients who are alive at the last study follow-up will be consored at that date. |
| Incidence of amputation | From enrollment to the end of study, planned 5 years after the last enrollment | The incidence of amputation will be defined as the time between the start of radiotherapy and the date of amputation regardless of the cause (progressive disease/recurrence, severe trophic complications, ...). Patients who were alive and free of amputation at the last follow-up will be censored at that date. Death without prior amputation will be considered as a competing event. Local or metastatic progression/recurrence will not be considered as a competing event. |
| Radiological response | From enrollment to the post radiotherapy MRI planned 3 to 4 weeks after the end of radiotherapy. | The radiological response to radiotherapy will assessed by comparing the post-radiotherapy MRI with the Baseline MRI according to the RECIST 1.1 criteria. The objective response will be defined as complete or partial response. |
| Tumor necrosis | From enrollment to the post radiotherapy MRI planned 3 to 4 weeks after the end of radiotherapy. | The percentage of tumor necrosis will be assessed on Baseline and post-radiotherapy MRI (using the larger slice plan). |
| Histological response | From enrollment to the surgery planned 6 +/- 2 weeks after the end of radiotherapy. | The histological response to radiotherapy will be assessed by determining the percentage of residual tumor in the resected specimen. Complete necrosis (\<5% residual tumor) will be distinguished. The percentage of hyalinisation, necrosis and fibrosis will also be assessed. |
| Quality of tumor resection | From enrollment to surgery planned 6 +/- 2 weekds after the end of the radiotherapy | The quality of tumor resection will be described regardless of the completeness of the resection. A complete tumor resection with histological confirmation of completeness and healthy margin will be described as "R0" ; A complete tumor resection with margin that may contain tumor will be described as "R1" ; Incomplete surgery will be described as "R2". |
| Morbidity | From enrollment to the end of study, planned 5 years after the last enrollment | The morbidity of treatments will be described using the NCI CTCAE v6.0 scale. This will include radiotherapy-related toxicity, from the first session of radiotherapy to the end of the study follow-up, surgical complication from the surgery to the end of the study follow-up, duration of hospitalisation, surgical reoperation, new hospitalisation for surgical complication and time to healing, during the entire study follow-up. |
| Limb function | From enrollment to the 5 years follow-up | Limb function will be assessed using the Musculoskeletal Tumor Society (MSTS). This questionnaire will be completed at registration, every 4 months for 2 years, then every 6 months for 3 years. |
| Quality of life with EORTC QLQ-C30 questionnaires | From enrollment to the 4 months follow-up | The quality of life will be assessed using the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30). The EORTC QLQ-C30 will be completed at registration, and at the first follow-up planned 4 months after the surgery. |
| Quality of life with EORTC QLQ-F17 questionnaires | From the first follow-up to the 5 years follow-up | The quality of life will be assessed using the EORTC QLQ-F17 questionnaires. During the follow-up, the QLQ-F17 will be completed every 4 months for 2 years, then every 6 months for 3 years. |
Countries
France
Contacts
CONTACTJulien THERY
PRINCIPAL_INVESTIGATORAbel CORDOBA, MD
Centre Oscar Lambret
Outcome results
None listed