Hypofractionated Radiotherapy With Hyperthermia in Unresectable or Marginally Resectable Soft Tissue Sarcomas

Phase 2

• Conditions: Fibrosarcoma; Sarcoma; Liposarcoma, Dedifferentiated; Leiomyosarcoma; Malignant Peripheral Nerve Sheath Tumors; Synovial Sarcoma; Undifferentiated Pleomorphic Sarcoma; Alveolar Soft Part Sarcoma; Clear Cell Sarcoma; Myxoid Liposarcoma
• Interventions: Radiation: Hypofractionated radiotherapy; Other: Hyperthermia

• Registration Number: NCT03989596
• Lead Sponsor: Maria Sklodowska-Curie National Research Institute of Oncology

Brief Summary

After a screening, which consists of biopsy, physical examination, initial diffusion-weighted magnetic resonance imaging (DWI-MRI) or body computed tomography (CT) scan, blood tests and case analysis on Multidisciplinary Team (MDT) meeting, a patient will receive the hypofractionated radiotherapy 10x 3.25 Gy with regional hyperthermia (twice a week) within two weeks. The response analysis in CT or DWI-MRI and toxicity assessment will be performed after at least 6 weeks. At the second MDT meeting, a final decision about resectability of the tumor will be made. In case of resectability or consent for amputation, if required, a patient will be referred to surgery. In case of unresectability or amputation refusal, the patient will receive the second part of the treatment which consists of 4x 4 Gy with hyperthermia (twice a week).

Detailed Description

There is a lack of standard treatment of unresectable and marginally resectable sarcomas. Results of commonly used approaches are unsatisfactory, especially in patients who are not candidates for neoadjuvant chemotherapy due to poor performance status, comorbidities, radioresistant pathology or disease progression on the commonly used chemotherapy regimens. The addition of regional hyperthermia to irradiation and in the prolonged gap between the end of hypofractionated 10x 3.25 Gy radiotherapy and surgery may allow obtaining the long-term local control with the maintenance of a good treatment tolerance.

Hypofractionation represents a variation of radiotherapy fractionation in which the total dose is divided into fewer fractions with an increased fraction dose. Such treatment may lead to additional biological effects when compared to conventionally fractionated radiotherapy (eg. vascular damage, increased immunogenicity, and antigenicity). The main advantages of hypofractionation are those related to the decreased overall treatment time which is more convenient for both patients and physicians, increased compliance and makes the treatment more cost-effective. Intriguing, such an approach may provide an additional benefit when treating non-radiosensitive tumors with a low alpha/beta ratio (eg. sarcomas).

Hyperthermia is a method of increasing the temperature in the tumor to damage cancer cells with minimum injury to the normal cells. It should be combined with another treatment modality (radio- or chemotherapy) rather than used alone. Its efficacy was proven in clinical trials. The treatment tolerance is usually very good.

Study Timeline

• Study Start: 2018-06-01
• Study First Submitted: 2019-06-14
• Study First Submitted QC: 2019-06-14
• Study First Posted: 2019-06-18
• Status Verified: 2020-12
• Primary Completion: 2020-12-31
• Last Update Submitted: 2021-01-27
• Last Update Posted: 2021-02-01
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Able to provide informed consent; age ≥18 years old
• Eastern Cooperative Oncology Group performance status 0 - 2
• Histologic diagnosis of locally advanced soft tissue sarcoma
• Marginally resectable or unresectable tumor (assessed at Multidisciplinary Tumor Board)
• Radioresistant sarcoma subtype (low-grade tumor or radioresistant histology) or contradictions to chemotherapy (assessed at Multidisciplinary Tumor Board) or progression after neoadjuvant chemotherapy

Exclusion Criteria

• Radiation-induced sarcoma or previous radiation to the affected volume
• Histologic diagnosis of rhabdomyosarcoma (except pleomorphic subtype), osteogenic sarcoma, Ewing's sarcoma/PNET, aggressive fibromatosis
• Contraindications to radiotherapy or hyperthermia
• Distant metastases

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Radiotherapy with hyperthermia	Hypofractionated radiotherapy	10x 3.25 Gy + hyperthermia + surgery or radiotherapy boost (4x 4 Gy + hyperthermia)
Radiotherapy with hyperthermia	Hyperthermia	10x 3.25 Gy + hyperthermia + surgery or radiotherapy boost (4x 4 Gy + hyperthermia)

Primary Outcome Measures

Name	Time	Method
Feasibility of the treatment schedule	Up to 3 months	The exact 95% confidence interval for an estimated feasibility proportion of 80% (23 of 30 patients) does not include (60-80%) a value of 50%. Thus, for a sample size of 30 patients, the feasibility of 80% is above chance level performance (50%).

Secondary Outcome Measures

Name	Time	Method
One-year progression-free survival	12 months after treatment completion
One-year sarcoma-specific survival	12 months after treatment completion
One-year local control rate	12 months after treatment completion
Rate of late toxicities	Two years after treatment completion	Rate of late toxicities of a planned schedule of therapy according to CTCAE 5.0

Trial Locations

Locations (1)

Maria Sklodowska-Curie Institute - Oncology Center; 🇵🇱 Warsaw, Mazovian, Poland