Clinical trial NCT03989596: Hypofractionated Radiotherapy With Hyperthermia in Unresectable or Marginally Resectable Soft Tissue Sarcomas
Official title: Hypofractionated Radiotherapy With Hyperthermia in Unresectable or Marginally Resectable Soft Tissue Sarcomas
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
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
Keywords: Dose Hypofractionation
Neoadjuvant Therapy
Sarcoma
Hyperthermia
Dose Fractionation
Lead sponsor: Maria Sklodowska-Curie National Research Institute of Oncology
Sponsor class: OTHER
First posted: 2019-06-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Feasibility of the treatment schedule
timeFrame: Up to 3 months
Secondary outcomes:
measure: One-year local control rate
timeFrame: 12 months after treatment completion
measure: One-year progression-free survival
timeFrame: 12 months after treatment completion
measure: One-year sarcoma-specific survival
timeFrame: 12 months after treatment completion
measure: Rate of late toxicities
timeFrame: Two years after treatment completion
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Institute - Oncology Center
state: Mazovian
Study officials:
affiliation: Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw
name: Mateusz J Spałek, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.