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出境医 / 临床实验 / Hypofractionated Radiotherapy With Hyperthermia in Unresectable or Marginally Resectable Soft Tissue Sarcomas (SINDIR)

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

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
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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
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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
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Poland
Maria Sklodowska-Curie Institute - Oncology Center
Warsaw, Mazovian, Poland, 02-781
Sponsors and Collaborators
Maria Sklodowska-Curie Institute - Oncology Center
Investigators
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Principal Investigator: Mateusz J Spałek, MD PhD Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw
Tracking Information
First Submitted Date  ICMJE June 14, 2019
First Posted Date  ICMJE June 18, 2019
Last Update Posted Date February 1, 2021
Actual Study Start Date  ICMJE June 1, 2018
Actual Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 27, 2021) 		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%).
Original Primary Outcome Measures  ICMJE
 (submitted: June 14, 2019) 		Rate of grade 3 or higher early toxicity of planned schedule of therapy according to RTOG/EORTC scale [ Time Frame: 12 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2021)
  • One-year local control rate [ Time Frame: 12 months after treatment completion ]
  • One-year progression-free survival [ Time Frame: 12 months after treatment completion ]
  • One-year sarcoma-specific survival [ Time Frame: 12 months after treatment completion ]
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2019)
  • One-year local control rate [ Time Frame: 24 months ]
  • One-year progression-free survival [ Time Frame: 24 months ]
  • One-year cancer-specific survival [ Time Frame: 24 months ]
  • Late treatment toxicity, at 6 and 12 months [ Time Frame: 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hypofractionated Radiotherapy With Hyperthermia in Unresectable or Marginally Resectable Soft Tissue Sarcomas
Official Title  ICMJE Hypofractionated Radiotherapy With Hyperthermia in Unresectable or Marginally Resectable Soft Tissue Sarcomas
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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.
Study Arms  ICMJE Experimental: Radiotherapy with hyperthermia
10x 3.25 Gy + hyperthermia + surgery or radiotherapy boost (4x 4 Gy + hyperthermia)
Interventions:
  • Radiation: Hypofractionated radiotherapy
  • Other: Hyperthermia
Publications *
  • Koseła-Paterczyk H, Szacht M, Morysiński T, Ługowska I, Dziewirski W, Falkowski S, Zdzienicki M, Pieńkowski 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. Review.
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 14, 2019) 		30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Actual Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Poland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03989596
Other Study ID Numbers  ICMJE SINDIR1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Responsible Party Maria Sklodowska-Curie Institute - Oncology Center
Study Sponsor  ICMJE Maria Sklodowska-Curie Institute - Oncology Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mateusz J Spałek, MD PhD Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw
PRS Account Maria Sklodowska-Curie Institute - Oncology Center
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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