Trial of Neoadjuvant Intensity-Modulated Radiation Therapy Followed by Surgery and Intraoperative Radiation Therapy in Resectable Retroperitoneal Soft Tissue Sarcoma (RETRO-WTS)

Study Overview
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Brief Summary
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Local control rates in patients with retroperitoneal soft tissue sarcoma (RSTS) remain disappointing even after gross total resection, mainly because wide margins are not achievable in the majority of patients. In contrast to extremity sarcoma, postoperative radiation therapy (RT) has shown limited efficacy due to its limitations in achievable dose and coverage. Although Intraoperative Radiation Therapy (IORT) has been introduced in some centers to overcome these dose limitations and resulted in improved outcome, local failure rates are still high even if considerable treatment related toxicity is accepted. As postoperative administration of RT has some general disadvantages, neoadjuvant approaches could offer benefits in terms of dose escalation, target coverage and reduction of toxicity, especially if highly conformal techniques like intensity-modulated radiation therapy (IMRT) are considered. Therefore the RETROWTS trials has been designed as a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant dose-escalated IMRT (50-56 Gy) followed by surgery and IORT (10-12 Gy) in patients with at least marginally resectable RSTS. The primary objective is the local control rate after five years. Secondary endpoints are progression-free and overall survival, acute and late toxicity, surgical resectability and patterns of failure. The aim of accrual is 37 patients in the per-protocol population.

Official Title
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Clinical Phase I/II Trial to Investigate Preoperative Dose-Escalated Intensity-Modulated Radiation Therapy (IMRT) and Intraoperative Radiation Therapy (IORT) in Patients With Retroperitoneal Soft Tissue Sarcoma

Conditions
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Retroperitoneal Soft Tissue Sarcoma

Intervention / Treatment
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* Radiation: Neoadjuvant intensity-modulated radiation therapy (IMRT)
* Radiation: intraoperative radiation therapy (IORT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written informed consent histologically confirmed, primary or locally recurrent soft tissue sarcoma of the retroperitoneal space judged as at least marginally resectable absence of distant metastases tumor size ≥ 5 cm Exclusion Criteria: missing written informed consent missing histological confirmation of soft tissue sarcoma Desmoid tumor (syn. aggressive fibromatosis) judged as gross incomplete or not resectable incomplete staging presence of distant metastases prior radiation therapy to the abdominal region participation in another clinical interventional study inflammatory bowel disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Neoadjuvant Intensity-Modulated Radiation Therapy Followed by Surgery and Intraoperative Radiation Therapy in Resectable Retroperitoneal Soft Tissue Sarcoma | Radiation: Neoadjuvant intensity-modulated radiation therapy (IMRT)<br>* neoadjuvant intensity-modulated radiation therapy, single dose 2.0-2.4 Gy, total dose 50-56 Gy<br>Radiation: intraoperative radiation therapy (IORT)<br>* during surgery, 10-12 Gy (90% isodose) to the tumor bed or residual disease<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Control Rate |  | 5 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | up to 5 years from first day of treatment | 
| Overall Survival |  | up to five years from first day of treatment | 
| Acute toxicity | scored according to CTCAE 3.0 | up to 3 months from first day of treatment | 
| Late Toxicity | scored according to CTCAE 3.0 and RTOG criteria | up to 5 years after first day of treatment | 
| Severe acute gastrointestinal toxicity | severe defined as grade >= III, scored according to CTC AE 3.0 | up to 3 months from first day of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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retroperitoneal soft tissue sarcoma, IMRT, IORT