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

NCT ID: NCT03989596

Last Updated: 2021-02-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-01
• Study Completion Date: 2022-12-31

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.

Conditions

Sarcoma; Alveolar Soft Part Sarcoma; Clear Cell Sarcoma; Malignant Peripheral Nerve Sheath Tumors; Myxoid Liposarcoma; Liposarcoma, Dedifferentiated; Synovial Sarcoma; Leiomyosarcoma; Undifferentiated Pleomorphic Sarcoma; Fibrosarcoma; Pleomorphic Rhabdomyosarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiotherapy with hyperthermia

10x 3.25 Gy + hyperthermia + surgery or radiotherapy boost (4x 4 Gy + hyperthermia)

Group Type: EXPERIMENTAL

Hypofractionated radiotherapy

Intervention Type: RADIATION

Preoperative hypofractionated 10x 3.25 Gy radiotherapy (5 consecutive days in a week, two weeks) prescribed on planned target volume (tumor volume + elective margins + setup/error margin) with daily image guidance with cone beam-CT or kV-portal position verification.

Radiotherapy boost 4x 4 Gy within one week in case of unresectability after 6 weeks.

Hyperthermia

Intervention Type: OTHER

Deep hyperthermia (Celsius TCS or BSD-2000) according to local protocol combined with radiotherapy, twice a week.

Interventions

Hypofractionated radiotherapy

Preoperative hypofractionated 10x 3.25 Gy radiotherapy (5 consecutive days in a week, two weeks) prescribed on planned target volume (tumor volume + elective margins + setup/error margin) with daily image guidance with cone beam-CT or kV-portal position verification.

Radiotherapy boost 4x 4 Gy within one week in case of unresectability after 6 weeks.

Intervention Type: RADIATION

Hyperthermia

Deep hyperthermia (Celsius TCS or BSD-2000) according to local protocol combined with radiotherapy, twice a week.

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Maria Sklodowska-Curie National Research Institute of Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mateusz J Spałek, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw

Locations

Maria Sklodowska-Curie Institute - Oncology Center

Warsaw, Mazovian, Poland

Countries

Poland

References

Kosela-Paterczyk H, Szacht M, Morysinski T, Lugowska I, Dziewirski W, Falkowski S, Zdzienicki M, Pienkowski A, Szamotulska K, Switaj T, Rutkowski P. Preoperative hypofractionated radiotherapy in the treatment of localized soft tissue sarcomas. Eur J Surg Oncol. 2014 Dec;40(12):1641-7. doi: 10.1016/j.ejso.2014.05.016. Epub 2014 Sep 20.

Reference Type: BACKGROUND

PMID: 25282099 (View on PubMed)

Lindner LH, Issels RD. Hyperthermia in soft tissue sarcoma. Curr Treat Options Oncol. 2011 Mar;12(1):12-20. doi: 10.1007/s11864-011-0144-6.

Reference Type: BACKGROUND

PMID: 21360087 (View on PubMed)

Pennacchioli E, Fiore M, Gronchi A. Hyperthermia as an adjunctive treatment for soft-tissue sarcoma. Expert Rev Anticancer Ther. 2009 Feb;9(2):199-210. doi: 10.1586/14737140.9.2.199.

Reference Type: BACKGROUND

PMID: 19192958 (View on PubMed)

Other Identifiers

SINDIR1

Identifier Type: -

Identifier Source: org_study_id