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

Sarcoma Clinical Trial

— SINDIR  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03989596
• Other study ID #: SINDIR1
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 1, 2018
• Est. completion date: December 31, 2022

Study information

• Verified date: December 2020
• Source: Maria Sklodowska-Curie Institute - Oncology Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alveolar Soft Part Sarcoma
• Clear Cell Sarcoma
• Fever
• Fibrosarcoma
• Histiocytoma, Malignant Fibrous
• Leiomyosarcoma
• Liposarcoma
• Liposarcoma, Dedifferentiated
• Liposarcoma, Myxoid
• Malignant Peripheral Nerve Sheath Tumors
• Myxoid Liposarcoma
• Nerve Sheath Neoplasms
• Pleomorphic Rhabdomyosarcoma
• Rhabdomyosarcoma
• Sarcoma
• Sarcoma, Alveolar Soft Part
• Sarcoma, Clear Cell
• Sarcoma, Synovial
• Synovial Sarcoma
• Undifferentiated Pleomorphic Sarcoma

Intervention

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.

Locations

Country	Name	City	State
Poland	Maria Sklodowska-Curie Institute - Oncology Center	Warsaw	Mazovian

Sponsors (1)

Lead Sponsor	Collaborator
Maria Sklodowska-Curie Institute - Oncology Center

Country where clinical trial is conducted

Poland, 

References & Publications (3)

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility of the treatment schedule	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%).	Up to 3 months
Secondary	One-year local control rate		12 months after treatment completion
Secondary	One-year progression-free survival		12 months after treatment completion
Secondary	One-year sarcoma-specific survival		12 months after treatment completion
Secondary	Rate of late toxicities	Rate of late toxicities of a planned schedule of therapy according to CTCAE 5.0	Two years after treatment completion