Radiotherapy With Hyperthermia in Recurrent and Radiation-Induced Sarcomas (HOT)

• ClinicalTrials.gov Identifier: NCT04398095
• Recruitment Status: Unknown
• First Posted: May 21, 2020
• Last Update Posted: April 28, 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 with radiation-induced or in-field recurrent sarcoma will receive the hypofractionated radiotherapy with deep hyperthermia (twice a week) within three weeks. The response analysis in CT or DWI-MRI and toxicity assessment will be performed after 6 weeks. In resectable tumors, a patient will be referred to surgery. In the case of unresectability, the patient will followed-up.

Condition or disease	Intervention/treatment	Phase
Radiation Induced Neoplasms; Radiation-Induced Cancer; Recurrent Sarcoma; Recurrent Soft Tissue Sarcoma	Radiation: Hypofractionated radiotherapy; Other: Hyperthermia; Radiation: Hypofractionated radiotherapy with boost	Phase 2

Detailed Description:

Due to the rarity of radiation-induced (RIS) or previously irradiated recurrent (PIRS) sarcomas, no guidelines nor randomized prospective clinical trials on this topic exist. Thus the management of RIS and PIR is challenging. The only curable modality in non-metastatic RIS/PIRS is radical resection with wide negative margins. The role of secondary radiotherapy in locally advanced RIS/PIRS is unclear, mostly due to the concerns about possible severe side effects after re-irradiation.

The addition of deep hyperthermia to irradiation and in the prolonged gap between the end of moderately hypofractionated radiotherapy (with or without integrated boost) and surgery may allow obtaining the long-term local control with the maintenance of a good treatment tolerance 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. Treatment tolerance is usually very good.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hyperthermia and Radiotherapy in the Treatment for In-field Recurrent and Radiation-induced Soft Tissue and Bone Sarcomas
• Actual Study Start Date: October 23, 2019
• Estimated Primary Completion Date: April 2022
• Estimated Study Completion Date: April 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Radiotherapy with hyperthermia in resectable sarcomas; 12x 3 Gy (4 fractions per week) + hyperthermia (6x) + surgery	Radiation: Hypofractionated radiotherapy; Resectable or marginally resectable tumors: preoperative hypofractionated 12x 3 Gy radiotherapy (4 days in a week, three 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.; Other: Hyperthermia; Deep hyperthermia (Celsius TCS or BSD-2000) according to local protocol combined with radiotherapy, twice a week.
Experimental: Radiotherapy with hyperthermia in non-resectable sarcomas; 12x 3 Gy with simultaneous integrated boost 3.5 Gy (4 fractions per week) + hyperthermia (6x)	Other: Hyperthermia; Deep hyperthermia (Celsius TCS or BSD-2000) according to local protocol combined with radiotherapy, twice a week.; Radiation: Hypofractionated radiotherapy with boost; Non-resectable/inoperable tumors: definitive hypofractionated 12x 3 Gy radiotherapy prescribed on planned target volume (tumor volume + elective margins + setup/error margin) with simultaneous integrated boost 3.5 Gy per fraction prescribed on boost planned target volume (tumor volume + setup/error margin), 4 days in a week, three weeks. Radiotherapy with daily image guidance with cone beam-CT or kV-portal position verification.

Outcome Measures

Primary Outcome Measures :

1. Ratio of late adverse events [ Time Frame: 18 months ]
   Ratio of grade 3 or higher late adverse events related to reirradiation, according to CTCAE 5.0

Secondary Outcome Measures :

1. Local control rate [ Time Frame: 18 months ]
2. Progression-free survival [ Time Frame: 18 months ]
3. Cancer-specific survival [ Time Frame: 18 months ]

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
• Eastern Cooperative Oncology Group performance status 0 - 2
• Age ≥18 years old
• Histologically-proven diagnosis of radiation-induced or recurrent soft tissue sarcoma
• Previous radiotherapy within the planned target volume

Exclusion Criteria:

• Histologic diagnosis of rhabdomyosarcoma (except spindle cell and pleomorphic subtype), osteogenic sarcoma, Ewing's sarcoma/PNET, aggressive fibromatosis
• Contraindications to radiotherapy or hyperthermia
• Predicted unacceptable high risk of reirradiation-related toxicity, in the Investigator's judgment
• Unresectable metastases

Contacts and Locations

Contacts

Contact: Mateusz J Spałek, MD PhD; +48225462455; mateusz.spalek@pib-nio.pl

Contact: Aneta Borkowska, MD; +48225462455; aneta.borkowska@pib-nio.pl

Locations

Poland

The Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw; Recruiting

Warsaw, Mazovian, Poland, 02-781

Contact: Mateusz J Spałek, MD PhD +48225462455 mateusz.spalek@pib-nio.pl

Sub-Investigator: Aneta Borkowska, MD

Principal Investigator: Mateusz J Spałek, MD PhD

Sub-Investigator: Piotr Ł Rutkowski, MD PhD

Sponsors and Collaborators

Maria Sklodowska-Curie National Research Institute of Oncology

Investigators

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

More Information

Publications:

de Jong MA, Oldenborg S, Bing Oei S, Griesdoorn V, Kolff MW, Koning CC, van Tienhoven G. Reirradiation and hyperthermia for radiation-associated sarcoma. Cancer. 2012 Jan 1;118(1):180-7. doi: 10.1002/cncr.26252. Epub 2011 Jun 28.

Haas RL, Miah AB, LePechoux C, DeLaney TF, Baldini EH, Alektiar K, O'Sullivan B. Preoperative radiotherapy for extremity soft tissue sarcoma; past, present and future perspectives on dose fractionation regimens and combined modality strategies. Radiother Oncol. 2016 Apr;119(1):14-21. doi: 10.1016/j.radonc.2015.12.002. Epub 2015 Dec 21.

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.

Borghede G, Hedelin H. Radiotherapy of localised prostate cancer. Analysis of late treatment complications. A prospective study. Radiother Oncol. 1997 May;43(2):139-46. doi: 10.1016/s0167-8140(96)01871-3.

• Responsible Party: Maria Sklodowska-Curie National Research Institute of Oncology
• ClinicalTrials.gov Identifier: NCT04398095
• Other Study ID Numbers: HOT1
• First Posted: May 21, 2020
• Last Update Posted: April 28, 2021
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Clinical Study Report (CSR)

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

Additional relevant MeSH terms:

Hyperthermia; Sarcoma; Neoplasms, Radiation-Induced; Recurrence; Disease Attributes; Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Body Temperature Changes; Heat Stress Disorders; Wounds and Injuries; Radiation Injuries