Hypofractionated Radiotherapy With Sequential Chemotherapy in Marginally Resectable Soft Tissue Sarcomas of Extremities or Trunk Wall (UN-RESARC)

January 19, 2021 updated by: Maria Sklodowska-Curie National Research Institute of Oncology

Hypofractionated 5x5 Gy Radiotherapy With Sequential Doxorubicin and Ifosfamide-based Chemotherapy in Marginally Resectable Soft Tissue Sarcomas of Extremities or Trunk Wall

After a screening, which consists of biopsy, physical examination, initial diffusion-weighted magnetic resonance imaging (DWI-MRI), body computed tomography (CT) scan, blood tests and case analysis on Multidisciplinary Team (MDT) meeting, a patient will receive the first course of chemotherapy - doxorubicin 75 mg/sqm and ifosfamide 10 g/sqm (AI regimen) with prophylactic mesna. Then a patient will be irradiated 5x5 Gy and after radiotherapy he or she will receive two courses of AI within 4-6 weeks, depending on the tolerance. Then the response analysis in DWI-MRI and toxicity assessment and will be performed. On the second MDT meeting, a final decision about resectability of the tumor will be made. In case of resectability, a patient will be referred to surgery.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

There is lack of standard treatment of marginally resectable sarcomas. Results of commonly used approaches are unsatisfactory. The addition of neoadjuvant/induction chemotherapy before the irradiation and in the prolonged gap between the end of hypofractionated 5x5 Gy radiotherapy and surgery may allow to obtain the R0 resection rate, high pathological response rate and/or a higher rate of limb-sparing/conservative surgery as well as to increase patients' survival.

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 what 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).

The basis of the study was a trial conducted by Kosela et al. in our center, which showed that preoperative short 5x5 Gy radiotherapy with immediate surgery is an effective and well-tolerated treatment of resectable sarcomas of extremities or trunk wall.

The rationale of chemotherapy comes from the interim analysis of a multicenter, international EORTC study comparing neoadjuvant systemic approaches in high-risk sarcomas. It was proven that AI regimen, which consists of ifosfamide and anthracyclines allowed to obtain 20% benefit in relapse-free survival and overall survival as compared to pathologically-tailored chemotherapy.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Poland
    • Mazovian
      • Warsaw, Mazovian, Poland, 02-781
        • Maria Sklodowska-Curie Institute - Oncology Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 98 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Able to provide informed consent
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
  • Age ≥18 years old
  • Histologic diagnosis of soft tissue sarcoma
  • Primary or recurrent tumor localized on extremities or trunk
  • Grade 2 or grade 3 tumor
  • Marginally resectable tumor as assessed by a multidisciplinary team
  • Adequate renal function (serum creatinine ≤ 1.5 ULN)
  • Adequate liver function (total bilirubin, AST, ALT 3x < ULN)

Exclusion Criteria:

  • Radiation-induced sarcoma
  • Second active malignancy, not including localized basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast; patients with a history of other malignancies are eligible if they have been continuously disease-free for > 10 years prior to the time of registration.
  • History of radiation to the affected volume
  • Histologic diagnosis of rhabdomyosarcoma (except pleomorphic subtype), angiosarcoma, epithelioid sarcoma, clear cell sarcoma, extraskeletal chondrosarcoma, alveolar soft part sarcoma, osteogenic sarcoma, Ewing's sarcoma/PPNET, aggressive fibromatosis, dermatofibrosarcoma protuberans
  • Contraindications to radiotherapy, chemotherapy or surgery
  • Metastatic disease except primary resectable isolated lung metastases

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sequential chemoradiotherapy
1xAI (doxorubicin 75 mg/sqm and ifosfamide 10 g/sqm) + 5x5 Gy radiotherapy + 2xAI + surgery
Drug: Sequential chemotherapy - 3 courses of AI
Three courses of doxorubicin and ifosfamide (AI, doxorubicin 75 mg/sqm and ifosfamide 10 g/sqm with prophylactic mesna), one before radiotherapy and two within the gap between radiotherapy and surgery.
Radiation: Hypofractionated radiotherapy
Preoperative hypofractionated 5x5 Gy radiotherapy (5 consecutive days) prescribed on planned target volume (tumor volume + elective margins + setup/error margin) with a daily image guidance with cone beam-CT-based position verification.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The ratio of en limb-sparing/conservative R0 resections.
Time Frame: 24 months
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiological response in diffusion-weighted MRI
Time Frame: 24 months
Radiological assessment of tumor change, especially diffusion parameters in DWI-MRI 6 weeks after the end of irradiation, according to the EORTC criteria.
24 months
Pathological response in resected tumors according to EORTC Soft Tissue and Bone Sarcoma Group criteria
Time Frame: 24 months
24 months
Toxicity of planned schedule of therapy according to CTCAE v.4.0.
Time Frame: 24 months after treatment completion
The study will be stopped prematurely if the rate of non-hematological toxicity grade 3 >30%
24 months after treatment completion
2-years overall survival
Time Frame: 24 months after treatment completion
24 months after treatment completion
2-years local control rate
Time Frame: 24 months after treatment completion
24 months after treatment completion

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of biomarkers in biopsy and post-operative material
Time Frame: 24 months
HIF-1 (hypoxia-inducible factor 1) - marker of hypoxia, predicting tumor response on radiotherapy; CD105/CD31/VEGF-A - tumor microvessel density; CD14, CD163, CD68KP i CD68 PG-M1 - tumor associated macrophages.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Maria Sklodowska-Curie National Research Institute of Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 11, 2017

Primary Completion (Actual)

December 31, 2019

Study Completion (Anticipated)

March 1, 2022

Study Registration Dates

First Submitted

August 27, 2018

First Submitted That Met QC Criteria

August 27, 2018

First Posted (Actual)

August 29, 2018

Study Record Updates

Last Update Posted (Actual)

January 22, 2021

Last Update Submitted That Met QC Criteria

January 19, 2021

Last Verified

December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • URESARC1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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