Surgical Timing After Preoperative Hypofractionated Radiotherapy for Localized Extremity and Trunk Soft Tissue Sarcoma (STARS)

January 2, 2026 updated by: Italian Sarcoma Group

Surgical Timing After Preoperative Hypofractionated Radiotherapy for Patients With Primary Localized Soft Tissue Sarcoma of the Extremity and Trunk: a Randomized Phase 2 Clinical Trial

Phase II, national, multicentric, prospective, randomized (1:1) non-inferiority trial with two parallel groups, incorporating a concurrent observational cohort of eligible non-randomized patients, designed to address critical knowledge gaps by prospectively evaluating the safety, efficacy, and feasibility of preoperative ultra-hypofractionated radiotherapy (HFRT) in patients with soft tissue sarcomas (STS) of the extremities and trunk.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is designed to address critical knowledge gaps by prospectively evaluating the safety, efficacy, and feasibility of preoperative ultra-hypofractionated radiotherapy (HFRT) in patients with soft tissue sarcomas (STS) of the extremities and trunk. Eligible patients will be randomized to receive an ultra-hypofractionated RT regimen consisting of 30 Gy delivered in 5 fractions of 6 Gy, followed by surgical resection at one of two predefined intervals: either 1-2 weeks or 4-6 weeks after completion of radiotherapy. In parallel, a non-randomized observational cohort will be recorded, consisting of patients treated according to current standard practice - surgery alone or surgery preceded by nonventional RT (50 Gy in 25 fractions) - to provide a contemporaneous benchmark for comparison. The aim of this study is to gather high-quality clinical evidence on the impact of ultra-hypofractionated RT on oncologic outcomes, treatment-related toxicity, perioperative morbidity, and patient-reported quality of life. Evaluation of logistical and economic implications of treatment de-escalation, such as healthcare resource utilization and treatment burden are also an important point to be addressed.

By systematically assessing these endpoints, this study aims to inform future clinical guidelines and support the potential integration of ultra-hypofractionated RT into routine clinical practice for selected patients with localized STS.

Study Type

Interventional

Enrollment (Estimated)

142

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Voluntary written informed consent, with the ability to fully understand and effectively communicate, before performance of any study-related procedure not part of normal medical practice, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • Age > 18 years
  • Proven diagnosis of primary, resectable extremity/trunk wall STS with low-medium risk (Sarculator© predicted 10y-OS > 60%)
  • Measurable disease criteria (RECIST 1.1 and CHOI)
  • ECOG: 0, 1 or 2 (if influenced by orthopedic condition and not by general status)
  • No major contraindication to the planned radiotherapy or surgical treatment
  • Active participation with adherence to requested treatment schedule and follow-up
  • Female subject will undergo a negative pregnancy test
  • Adequate bone marrow function (hemoglobin > 9g/dL, Leukocytes > 3000/mm³, platelets > 100,000/mm³). Patients with plasma creatinine ≤ 1.6 mg/dL, transaminase (AST-SGOT, ALT-SGPT) ≤ 2.5 times the UNL; total bilirubin ≤ 1.5 time the UNL; alkaline phosphatase ≤ 2.5 times the UNL are acceptable. CRP, LDH, total protein and albumin must also be recorded.
  • HBV and HCV serologies must be performed prior to patient inclusion. If hepatitis B surface antigen (HBsAg) is positive, further evaluation is required to exclude active viral replication (i.e., testing for hepatitis B e antigen [HBeAg] and HBV DNA). If either of these markers is positive, study inclusion is not recommended. In such cases, prophylactic treatment with lamivudine may be considered at the investigator's discretion. If a potential participant tests positive for anti-HCV antibodies, active infection must be ruled out through a qualitative HCV PCR test. If PCR testing cannot be performed, or if it confirms active infection, the patient will not be eligible for the study. Patients must be HIV-seronegative, with a CD4+ T-cell count greater than 400/mm³. Individuals with clinically significant immunodeficiency-either congenital or acquired-are not eligible for enrollment

Exclusion Criteria:

  • Age < 18y
  • Soft tissue sarcomas (STS) originating at different sites (i.e., retroperitoneal, abdominal, pelvic, head and neck), gynecological sarcomas, as well as gastrointestinal stromal tumors (GISTs), desmoid-type fibromatosis and pediatric-type sarcomas (i.e., extraosseous Ewing sarcoma, embryonal/alveolar rhabdomyosarcoma, desmoplastic small round cell tumor) are excluded.
  • Recurrent or metastatic condition or previous whoop-surgery for sarcoma (incisional biopsies are allowed if performed 6 months before referral).
  • Unresectable tumors (with limb sparing surgery)
  • Diagnosed oncological condition in the 5 years before enrollment (exceptions: Gleason <6 prostatic adenocarcinoma; In-situ cervical cancer and melanoma; basal cell skin carcinoma radically treated)
  • Prior radiation treatment to the site designated for planned surgery or radiotherapy, regardless of indication
  • Any medical condition that can impair and reduce life expectancy to less than 2 years including but not limited to significant systemic diseases grade 3 or higher on the CI-CTCAE v5.0 scale, that limit patient availability, or according to investigator judgment may contribute significantly to treatment toxicity
  • Uncontrolled bacterial, fungal, or viral infections-either systemic or localized at the site of planned surgery or radiotherapy
  • Severe psychiatric disorder, psychological, familial, social or geographic circumstances that limit the patient's ability to comply with the protocol or informed consent.
  • Patients who had participated in another clinical trial and/or had received any other investigational product in the last 30 days prior to inclusion
  • Patients who had received any other treatment for the disease under study including chemotherapy, radiotherapy, surgery or any other treatment with curative intent. incisional biopsies are allowed if performed 6 months before referral.
  • Inability to comply with the requested follow-up
  • Women who are pregnant or breast-feeding
  • Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
  • BMI > 40 and BMI < 18

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A
hypofractionated radiotherapy (30Gy/5 fractions) and surgical resection at 1-2 weeks after treatment.
Procedure: hypofractionated radiotherapy (30Gy/5 fractions) and surgical resection at 1-2 weeks after treatment
hypofractionated radiotherapy (30Gy/5 fractions) and surgical resection at 1-2 weeks after treatment
Experimental: Group B
hypofractionated radiotherapy (30Gy/5 fractions) and surgical resection at 4-6 weeks after treatment.
Procedure: hypofractionated radiotherapy (30Gy/5 fractions) and surgical resection at 4-6 weeks after treatment
hypofractionated radiotherapy (30Gy/5 fractions) and surgical resection at 4-6 weeks after treatment
No Intervention: Observational cohort
Standard treatment with surgery ± standard radiotherapy (50Gy/25 fractions)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the incidence of postoperative complications
Time Frame: Day of surgery (DOS); 7-14-21-30-60-90 days post DOS; 4-8-12-16-20-24 months post DOS
The primary objective of this study is to determine the incidence of postoperative complications (according to Clavien-Dindo) within 90 days from surgery
Day of surgery (DOS); 7-14-21-30-60-90 days post DOS; 4-8-12-16-20-24 months post DOS

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of Life (QoL)
Time Frame: At last available QoL assessment date for patients without confirmed deterioration
Quality of Life (QoL)
At last available QoL assessment date for patients without confirmed deterioration
Overall Survival (OS)
Time Frame: At the last date that patient was known to be alive
Overall Survival (OS)
At the last date that patient was known to be alive
Disease-Free Survival (DFS)
Time Frame: Months 4-8-12-16-20-24 post surgery
Disease-Free Survival (DFS)
Months 4-8-12-16-20-24 post surgery
Cumulative Incidence of Local Recurrence (CCI-LR)
Time Frame: Months 4-8-12-16-20-24 post surgery
Cumulative Incidence of Local Recurrence (CCI-LR)
Months 4-8-12-16-20-24 post surgery
Cumulative Incidence of Distant Metastasis (CCI-DM)
Time Frame: Months 4-8-12-16-20-24 post surgery
Cumulative Incidence of Distant Metastasis (CCI-DM)
Months 4-8-12-16-20-24 post surgery
Pathological response
Time Frame: At any time during the study
Pathological response
At any time during the study
Radiological response (RECIST 1.1 and CHOI)
Time Frame: Months 4-8-12-16-20-24 post surgery
Radiological response (RECIST 1.1 and CHOI)
Months 4-8-12-16-20-24 post surgery
Treatment-related toxicity
Time Frame: 7-14-21-30-60-90 days DOS, 4-8-12-16-20-24 months post DOS
Treatment-related toxicity (based on Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0)
7-14-21-30-60-90 days DOS, 4-8-12-16-20-24 months post DOS
Postoperative complications
Time Frame: 7-14-21-30-60-90 days DOS, 4-8-12-16-20-24 months post DOS
Postoperative complications (classified according to Clavien-Dindo and CCI)
7-14-21-30-60-90 days DOS, 4-8-12-16-20-24 months post DOS

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Italian Sarcoma Group

Collaborators

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Investigators

  • Principal Investigator: Marco Baia, MD, Findazione IRCCS Istituto Nazionale Tumori Milano

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 30, 2026

Primary Completion (Estimated)

December 1, 2029

Study Completion (Estimated)

December 1, 2035

Study Registration Dates

First Submitted

November 17, 2025

First Submitted That Met QC Criteria

November 24, 2025

First Posted (Estimated)

December 5, 2025

Study Record Updates

Last Update Posted (Actual)

January 6, 2026

Last Update Submitted That Met QC Criteria

January 2, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STARS (STaRS)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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