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

• ClinicalTrials.gov Identifier: NCT03989596
• Recruitment Status: Unknown
• First Posted: June 18, 2019
• Last Update Posted: February 1, 2021
• Sponsor: Maria Sklodowska-Curie National Research Institute of Oncology
• Information provided by (Responsible Party): Maria Sklodowska-Curie National Research Institute of Oncology

Study Description

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).

Condition or disease	Intervention/treatment	Phase
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	Radiation: Hypofractionated radiotherapy; Other: Hyperthermia	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hypofractionated Radiotherapy With Hyperthermia in Unresectable or Marginally Resectable Soft Tissue Sarcomas
• Actual Study Start Date: June 1, 2018
• Actual Primary Completion Date: December 31, 2020
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: Radiotherapy with hyperthermia; 10x 3.25 Gy + hyperthermia + surgery or radiotherapy boost (4x 4 Gy + hyperthermia)

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

Outcome Measures

Primary Outcome Measures :

1. Feasibility of the treatment schedule [ Time Frame: 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 :

1. One-year local control rate [ Time Frame: 12 months after treatment completion ]
2. One-year progression-free survival [ Time Frame: 12 months after treatment completion ]
3. One-year sarcoma-specific survival [ Time Frame: 12 months after treatment completion ]
4. Rate of late toxicities [ Time Frame: Two years after treatment completion ]
   Rate of late toxicities of a planned schedule of therapy according to CTCAE 5.0

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Poland

Maria Sklodowska-Curie Institute - Oncology Center

Warsaw, Mazovian, Poland, 02-781

Sponsors and Collaborators

Maria Sklodowska-Curie National Research Institute of Oncology

Investigators

• Principal Investigator: Mateusz J Spałek, MD PhD; Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw

More Information

Publications:

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.

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.

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.

• Responsible Party: Maria Sklodowska-Curie National Research Institute of Oncology
• ClinicalTrials.gov Identifier: NCT03989596
• Other Study ID Numbers: SINDIR1
• First Posted: June 18, 2019
• Last Update Posted: February 1, 2021
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All IPD that underlie results in a publication as supplementary materials
• Time Frame: Data will be available since a publication (as a study supplementary material)
• Access Criteria: Based on journal policy, open access is preferred

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Maria Sklodowska-Curie National Research Institute of Oncology:

Dose Hypofractionation; Neoadjuvant Therapy; Sarcoma; Hyperthermia; Dose Fractionation

Additional relevant MeSH terms:

Hyperthermia; Fever; Sarcoma; Rhabdomyosarcoma; Leiomyosarcoma; Liposarcoma; Sarcoma, Synovial; Nerve Sheath Neoplasms; Neurofibrosarcoma; Fibrosarcoma; Sarcoma, Alveolar Soft Part; Histiocytoma, Malignant Fibrous; Sarcoma, Clear Cell; Liposarcoma, Myxoid; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Myosarcoma; Neoplasms, Muscle Tissue; Body Temperature Changes; Heat Stress Disorders; Wounds and Injuries; Neoplasms, Adipose Tissue; Neoplasms, Connective Tissue; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases