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A Study of IMRT in Primary Bone and Soft Tissue Sarcoma (IMRiS)

Primary Purpose

Soft Tissue Sarcoma, Adult, Ewing Sarcoma, Bone Sarcoma

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Intensity modulated radiotherapy (IMRT)
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Soft Tissue Sarcoma, Adult focused on measuring Intensity Modulated Radiotherapy, Radiotherapy

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Histologically proven soft tissue sarcoma of the upper or lower limb or limb girdle (Cohort 1), OR,

    Ewing sarcoma of bone arising in the pelvis or spine (Cohort 2) , OR,

    High grade primary bone sarcoma (non-Ewing) or Chordoma arising in the pelvis/spine (Cohort 3)

  2. Patients requiring (neo)adjuvant or definitive radical radiotherapy
  3. WHO performance status 0-2
  4. Patients aged 16 years or more
  5. Patients fit enough to undergo radiotherapy treatment and willing to attend follow up visits as per protocol
  6. Women of child-bearing potential must have a negative pregnancy test prior to trial entry. Female patients of child-bearing potential and male patients with partners of child-bearing potential must agree to use adequate contraception methods, which must be continued for 3 months after completion of treatment.
  7. Capable of giving written informed consent

Exclusion Criteria:

  1. Previous radiotherapy to the same site
  2. Patients receiving concurrent chemotherapy with radiotherapy (neo-adjuvant chemotherapy prior to radiotherapy is permitted.
  3. Patient with bone sarcomas eligible for proton beam radiotherapy; N.B. if a patient is not to have PBRT for whatever reason, they may be considered for IMRiS.
  4. Paediatric type alveolar or embryonal rhabdomyosarcomas
  5. Pregnancy (Women of child-bearing potential must have a negative pregnancy test prior to trial entry. Female patients of child-bearing potential and male patients with partners of child-bearing potential must agree to use adequate contraception methods, which must be continued for 3 months after completion of treatment
  6. Patients with concurrent or previous malignancy that could compromise assessment of the primary and secondary endpoints of the trial; these cases must be discussed with UCL CTC prior to the patient being approached.

Sites / Locations

  • St Luke's Hospital
  • Clatterbridge Cancer Centre
  • Belfast City Hospital
  • Queen Elizabeth Hospital
  • Bristol Haematology and Oncology Centre
  • Adenbrookes' Hospital
  • Velindre Hospital
  • Cheltenham Hospital
  • University Hospital Coventry
  • Royal Derby Hospital
  • Western General Hospital
  • Royal Devon & Exeter Foundation Trust
  • Beatson West of Scotland Cancer Centre
  • St James' Institute of Oncology
  • Leicester Royal Infirmary
  • University College London Hospitals
  • The Christie Hospital
  • Northern Centre for Cancer Care
  • Northampton General Hospital
  • Norfolk and Norwich University Hospital
  • Nottingham City Hospital
  • Churchill Hospital
  • Derriford Hospital
  • Royal Preston Hospital
  • Weston Park Hospital
  • Southampton General Hospital
  • The Royal Marsden NHS Foundation Trust
  • Singleton Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

Cohort 1 (closed to recruitment)

Cohort 2

Cohort 3

Arm Description

Cohort 1: Patients with Limb/limb girdle soft tissue sarcoma (STS) receiving (neo)-adjuvant radiotherapy (Intensity Modulated Radiotherapy) Dose schedules for Cohort 1: Pre-operative RT - 50 Gy in 25 daily fractions over 5 weeks Post-operative RT - 60 Gy in 30 daily fractions to the high dose planning target volume (PTV) and 52.2 Gy in 30 daily fractions to the low dose PTV treated concurrently over 6 weeks Post-operative RT (positive resection margins) - 66 Gy in 33 daily fractions to the high dose PTV, and 53.46Gy in 33 fractions to the low dose PTV treated concurrently over 6 ½ weeks.

Cohort 2: Patients with Ewing sarcoma of the spine/pelvis receiving definitive radical or (neo)-adjuvant radiotherapy (Intensity Modulated Radiotherapy) Dose schedules for Cohort 2: Pre-operative RT - 50.4 Gy in 28 daily fractions over 5½ weeks Post-operative RT - 54 Gy in 30 daily fractions over 6 weeks Primary RT - 54 Gy in 30 daily fractions over 6 weeks.

Cohort 3: Patients with non-Ewing primary bone sarcomas of the spine/pelvis receiving definitive radical or adjuvant Radiotherapy (Intensity Modulated Radiotherapy) Dose schedule for Cohort 3: Primary RT - 70 Gy in 35 daily fractions over 7 week Post-operative RT (non-chordoma) - primary bone sarcoma 60 Gy in 30 daily fractions over 6 weeks Post-operative RT (chordoma) - 70 Gy in 35 daily fractions over 7 weeks.

Outcomes

Primary Outcome Measures

Cohort 1 (limb soft tissue sarcomas): The rate of grade 2 or more late soft tissue fibrosis at 2 years following radiotherapy as assessed by RTOG late radiation morbidity criteria.
Late toxicity assessment measured using RTOG late radiation morbidity criteria.
Cohorts 2 (Ewing's sarcoma of the spine/pelvis): The proportion of patients in whom 90% of the planPTV receives 95% of the optimal prescription dose.
Cohorts 2 (Ewing's sarcoma of the spine/pelvis): The proportion of patients in whom 90% of the planPTV receives 95% of the optimal prescription dose.
Cohort 3 (Non-Ewing's primary bone sarcomas of the spine/pelvis): The proportion of patients in whom 80% of the planPTV receives 95% of the optimal prescription dose.
Cohort 3 (Non-Ewing's primary bone sarcomas of the spine/pelvis): The proportion of patients in whom 80% of the planPTV receives 95% of the optimal prescription dose.

Secondary Outcome Measures

Acute RT toxicity - (For all cohorts)
In all 3 cohorts, Acute RT toxicity measured using RTOG acute radiation morbidity criteria.
Late RT toxicity - (For all cohorts)
In all 3 cohorts, late toxicities measured using the RTOG/EORTC Late Radiation Morbidity Scoring Criteria (skin, subcutaneous tissue fibrosis, bone, joint stiffness) and Stern's scale for oedema
Patient reported Quality of life (QOL) - (All cohorts)
All cohorts, patient reported Quality of life measured using EORTC QLQ-C30 quality of life questionnaire
Patient reported limb function (Cohort 1 only)
For patients in Cohort 1 only, patient reported limb function measured using TESS questionnaire
Disease free survival (All Cohorts)
Disease free survival will be calculated from the date of registration to date of documented disease progression, or death from any cause. Where progression is suspected and subsequently confirmed by scans, the date of documented suspected progression will be used. Patients alive and disease-free will be censored at the date last seen.
Overall survival (All Cohorts)
Overall survival time will be calculated from date of registration to the date of death from any cause or end of trial follow up
Time to local tumour recurrence (All Cohorts, for adjuvant RT)
Time to local tumour recurrence evaluation from date of registration to first diagnosis of recurrence (histological or radiological).
Time to local disease progression (Cohorts 2 and 3, for definitive radical RT)
Time to local disease progression evaluation from date of registration to first diagnosis of progression.
Response by RECIST 1.1 (Cohorts 2 and 3, for definitive radical RT)
Response measured according to RECIST v 1.1 (for definitive radical RT)
Wound complications within 120 days of surgery (Cohort 1 only)
Rate and severity of wound complications assessed up to 120 days post surgery. This is a composite outcome measure assessed by a clinical examination of the wound.
For individual plans (cohort 2 & 3)
Percentage volume of planPTV receiving 95% of the prescription dose (50.4Gy/54Gy for cohort 2 and 60Gy/70Gy for cohort 3)
For individual plans (cohort 2 & 3)
Dose delivered to 95%, 80%, 70%, 60% and 50% volume of planPTV.

Full Information

First Posted
July 31, 2015
Last Updated
December 1, 2020
Sponsor
University College, London
Collaborators
Cancer Research UK, NCRI Radiotherapy Trials QA (RTTQA) Group
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1. Study Identification

Unique Protocol Identification Number
NCT02520128
Brief Title
A Study of IMRT in Primary Bone and Soft Tissue Sarcoma
Acronym
IMRiS
Official Title
A Phase II Study of Intensity Modulated Radiotherapy (IMRT) for Patients With Primary Bone and Soft Tissue Sarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
March 2016 (Actual)
Primary Completion Date
June 30, 2020 (Actual)
Study Completion Date
June 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
Collaborators
Cancer Research UK, NCRI Radiotherapy Trials QA (RTTQA) Group

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
IMRiS is a phase II trial which aims to assess the feasibility, efficacy and toxicity of Intensity Modulated Radiotherapy (IMRT) in three different cohorts of patients with primary bone and soft tissue sarcoma and to demonstrate whether IMRT can improve on current clinical outcomes. Cohort 1 of the trial is now closed to recruitment.
Detailed Description
IMRiS is a prospective multicentre phase II trial of Intensity Modulated Radiotherapy (IMRT). The trial is aiming to evaluate the role of intensity modulated radiotherapy (IMRT) in soft tissue and bone sarcomas. Three separate sarcoma cohorts will be studied and will be analysed separately. Patients will be enrolled in one of three cohorts depending on the type of sarcoma they have: Cohort 1- Patients with Limb/limb girdle soft tissue sarcoma receiving (neo)-adjuvant radiotherapy. (closed to recruitment) Cohort 2- Patients with Ewing sarcoma of the spine/pelvis receiving definitive radical or (neo)-adjuvant radiotherapy. Cohort 3- Patients with non-Ewing primary bone sarcomas of the spine/pelvis receiving definitive radical or adjuvant radiotherapy. Dose schedules for each Cohort have been indicated in the Trial Arm description. Radiotherapy will be delivered with fixed beam IMRT, arc IMRT techniques, or tomotherapy. All trial patients will be followed up until death or a maximum of three years from the date of registration in the trial. The theoretical advantage to IMRT is the potential reduction in late toxicity and subsequent potential for functional improvement. There have been no prospective studies to date powered to address this, particularly where IMRT is used post-operatively. IMRiS cohort 1 will address this question and establish if the use of IMRT will reduce late normal tissue toxicity. In cohorts 2 & 3, the aim is to establish if the use of IMRT will enable the achievement of a radiotherapy treatment plan that delivers the optimal dose while keeping within normal tissue tolerances. There have been no clinical trials of IMRT in Ewing sarcoma and there is very little published on the use of IMRT in high grade bone sarcomas and chordomas. It is important to establish the feasibility of IMRT to achieve the required radiation doses to the tumour, and to prospectively document the side effects of treatment in this setting. IMRiS will address this in cohort 2 and cohort 3.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Soft Tissue Sarcoma, Adult, Ewing Sarcoma, Bone Sarcoma, Chordoma
Keywords
Intensity Modulated Radiotherapy, Radiotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
191 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1 (closed to recruitment)
Arm Type
Other
Arm Description
Cohort 1: Patients with Limb/limb girdle soft tissue sarcoma (STS) receiving (neo)-adjuvant radiotherapy (Intensity Modulated Radiotherapy) Dose schedules for Cohort 1: Pre-operative RT - 50 Gy in 25 daily fractions over 5 weeks Post-operative RT - 60 Gy in 30 daily fractions to the high dose planning target volume (PTV) and 52.2 Gy in 30 daily fractions to the low dose PTV treated concurrently over 6 weeks Post-operative RT (positive resection margins) - 66 Gy in 33 daily fractions to the high dose PTV, and 53.46Gy in 33 fractions to the low dose PTV treated concurrently over 6 ½ weeks.
Arm Title
Cohort 2
Arm Type
Other
Arm Description
Cohort 2: Patients with Ewing sarcoma of the spine/pelvis receiving definitive radical or (neo)-adjuvant radiotherapy (Intensity Modulated Radiotherapy) Dose schedules for Cohort 2: Pre-operative RT - 50.4 Gy in 28 daily fractions over 5½ weeks Post-operative RT - 54 Gy in 30 daily fractions over 6 weeks Primary RT - 54 Gy in 30 daily fractions over 6 weeks.
Arm Title
Cohort 3
Arm Type
Other
Arm Description
Cohort 3: Patients with non-Ewing primary bone sarcomas of the spine/pelvis receiving definitive radical or adjuvant Radiotherapy (Intensity Modulated Radiotherapy) Dose schedule for Cohort 3: Primary RT - 70 Gy in 35 daily fractions over 7 week Post-operative RT (non-chordoma) - primary bone sarcoma 60 Gy in 30 daily fractions over 6 weeks Post-operative RT (chordoma) - 70 Gy in 35 daily fractions over 7 weeks.
Intervention Type
Radiation
Intervention Name(s)
Intensity modulated radiotherapy (IMRT)
Intervention Description
Intensity modulated radiotherapy (IMRT) is an advanced radiotherapy technique that is able to deliver a highly conformal dose to a target with improved sparing of the surrounding normal tissues from moderate to high radiation doses. IMRT is likely to be of particular benefit for tumours that have complex shapes, or those in close proximity to sensitive normal tissues and critical organs. Reducing the dose to normal tissues may in turn reduce the acute and late side effects of treatment. IMRT can be delivered from multiple fixed beam angles or through rotational arc applications such as volumetric modulated arc therapy (VMAT) and tomotherapy. The radiotherapy is delivered using multiple small beams (beamlets) of non-uniform intensity.
Primary Outcome Measure Information:
Title
Cohort 1 (limb soft tissue sarcomas): The rate of grade 2 or more late soft tissue fibrosis at 2 years following radiotherapy as assessed by RTOG late radiation morbidity criteria.
Description
Late toxicity assessment measured using RTOG late radiation morbidity criteria.
Time Frame
From date of registration until 2 years after date of registration.
Title
Cohorts 2 (Ewing's sarcoma of the spine/pelvis): The proportion of patients in whom 90% of the planPTV receives 95% of the optimal prescription dose.
Description
Cohorts 2 (Ewing's sarcoma of the spine/pelvis): The proportion of patients in whom 90% of the planPTV receives 95% of the optimal prescription dose.
Time Frame
Upon completion of IMRT treatment
Title
Cohort 3 (Non-Ewing's primary bone sarcomas of the spine/pelvis): The proportion of patients in whom 80% of the planPTV receives 95% of the optimal prescription dose.
Description
Cohort 3 (Non-Ewing's primary bone sarcomas of the spine/pelvis): The proportion of patients in whom 80% of the planPTV receives 95% of the optimal prescription dose.
Time Frame
Upon completion of IMRT treatment
Secondary Outcome Measure Information:
Title
Acute RT toxicity - (For all cohorts)
Description
In all 3 cohorts, Acute RT toxicity measured using RTOG acute radiation morbidity criteria.
Time Frame
From date of registration up to 90 days after date of registration
Title
Late RT toxicity - (For all cohorts)
Description
In all 3 cohorts, late toxicities measured using the RTOG/EORTC Late Radiation Morbidity Scoring Criteria (skin, subcutaneous tissue fibrosis, bone, joint stiffness) and Stern's scale for oedema
Time Frame
From Day 91 after date of registration up to 3 years after date of registration
Title
Patient reported Quality of life (QOL) - (All cohorts)
Description
All cohorts, patient reported Quality of life measured using EORTC QLQ-C30 quality of life questionnaire
Time Frame
Timepoints- Baseline, 1 year and 2 year post treatment
Title
Patient reported limb function (Cohort 1 only)
Description
For patients in Cohort 1 only, patient reported limb function measured using TESS questionnaire
Time Frame
At timepoints - Baseline, 1 year and 2 years post Treatment
Title
Disease free survival (All Cohorts)
Description
Disease free survival will be calculated from the date of registration to date of documented disease progression, or death from any cause. Where progression is suspected and subsequently confirmed by scans, the date of documented suspected progression will be used. Patients alive and disease-free will be censored at the date last seen.
Time Frame
The start date for analysis will be the date of registration. From date of registration to date of documented disease progression assessed up to 3 years from date of registration
Title
Overall survival (All Cohorts)
Description
Overall survival time will be calculated from date of registration to the date of death from any cause or end of trial follow up
Time Frame
From date of registration to date of death or date of last follow-up assessment (assessed up to 3 years from date of registration)
Title
Time to local tumour recurrence (All Cohorts, for adjuvant RT)
Description
Time to local tumour recurrence evaluation from date of registration to first diagnosis of recurrence (histological or radiological).
Time Frame
From date of registration to date of documented recurrence within the irradiated site (assessed up to 3 years from date of registration)
Title
Time to local disease progression (Cohorts 2 and 3, for definitive radical RT)
Description
Time to local disease progression evaluation from date of registration to first diagnosis of progression.
Time Frame
From date of registration to date of documented progression (assessed up to 3 years from date of registration)
Title
Response by RECIST 1.1 (Cohorts 2 and 3, for definitive radical RT)
Description
Response measured according to RECIST v 1.1 (for definitive radical RT)
Time Frame
From date of registration to date of documented progression (assessed up to 3 years from date of registration)
Title
Wound complications within 120 days of surgery (Cohort 1 only)
Description
Rate and severity of wound complications assessed up to 120 days post surgery. This is a composite outcome measure assessed by a clinical examination of the wound.
Time Frame
From date of definitive surgery until 120 days post surgery
Title
For individual plans (cohort 2 & 3)
Description
Percentage volume of planPTV receiving 95% of the prescription dose (50.4Gy/54Gy for cohort 2 and 60Gy/70Gy for cohort 3)
Time Frame
Upon completion of IMRT treatment.
Title
For individual plans (cohort 2 & 3)
Description
Dose delivered to 95%, 80%, 70%, 60% and 50% volume of planPTV.
Time Frame
Upon completion of IMRT treatment.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically proven soft tissue sarcoma of the upper or lower limb or limb girdle (Cohort 1), OR, Ewing sarcoma of bone arising in the pelvis or spine (Cohort 2) , OR, High grade primary bone sarcoma (non-Ewing) or Chordoma arising in the pelvis/spine (Cohort 3) Patients requiring (neo)adjuvant or definitive radical radiotherapy WHO performance status 0-2 Patients aged 16 years or more Patients fit enough to undergo radiotherapy treatment and willing to attend follow up visits as per protocol Women of child-bearing potential must have a negative pregnancy test prior to trial entry. Female patients of child-bearing potential and male patients with partners of child-bearing potential must agree to use adequate contraception methods, which must be continued for 3 months after completion of treatment. Capable of giving written informed consent Exclusion Criteria: Previous radiotherapy to the same site Patients receiving concurrent chemotherapy with radiotherapy (neo-adjuvant chemotherapy prior to radiotherapy is permitted. Patient with bone sarcomas eligible for proton beam radiotherapy; N.B. if a patient is not to have PBRT for whatever reason, they may be considered for IMRiS. Paediatric type alveolar or embryonal rhabdomyosarcomas Pregnancy (Women of child-bearing potential must have a negative pregnancy test prior to trial entry. Female patients of child-bearing potential and male patients with partners of child-bearing potential must agree to use adequate contraception methods, which must be continued for 3 months after completion of treatment Patients with concurrent or previous malignancy that could compromise assessment of the primary and secondary endpoints of the trial; these cases must be discussed with UCL CTC prior to the patient being approached.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Beatrice Seddon, Ph.D., M.D
Organizational Affiliation
University College London Hospitals
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Luke's Hospital
City
Dublin
Country
Ireland
Facility Name
Clatterbridge Cancer Centre
City
Bebington
Country
United Kingdom
Facility Name
Belfast City Hospital
City
Belfast
Country
United Kingdom
Facility Name
Queen Elizabeth Hospital
City
Birmingham
Country
United Kingdom
Facility Name
Bristol Haematology and Oncology Centre
City
Bristol
Country
United Kingdom
Facility Name
Adenbrookes' Hospital
City
Cambridge
Country
United Kingdom
Facility Name
Velindre Hospital
City
Cardiff
ZIP/Postal Code
CF5 6SH
Country
United Kingdom
Facility Name
Cheltenham Hospital
City
Cheltenham
Country
United Kingdom
Facility Name
University Hospital Coventry
City
Coventry
Country
United Kingdom
Facility Name
Royal Derby Hospital
City
Derby
ZIP/Postal Code
DE22 3NE
Country
United Kingdom
Facility Name
Western General Hospital
City
Edinburgh
Country
United Kingdom
Facility Name
Royal Devon & Exeter Foundation Trust
City
Exeter
ZIP/Postal Code
EX2 5DW
Country
United Kingdom
Facility Name
Beatson West of Scotland Cancer Centre
City
Glasgow
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Facility Name
St James' Institute of Oncology
City
Leeds
Country
United Kingdom
Facility Name
Leicester Royal Infirmary
City
Leicester
Country
United Kingdom
Facility Name
University College London Hospitals
City
London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Facility Name
The Christie Hospital
City
Manchester
Country
United Kingdom
Facility Name
Northern Centre for Cancer Care
City
Newcastle
Country
United Kingdom
Facility Name
Northampton General Hospital
City
Northampton
Country
United Kingdom
Facility Name
Norfolk and Norwich University Hospital
City
Norwich
ZIP/Postal Code
NR4 7UY
Country
United Kingdom
Facility Name
Nottingham City Hospital
City
Nottingham
Country
United Kingdom
Facility Name
Churchill Hospital
City
Oxford
Country
United Kingdom
Facility Name
Derriford Hospital
City
Plymouth
Country
United Kingdom
Facility Name
Royal Preston Hospital
City
Preston
Country
United Kingdom
Facility Name
Weston Park Hospital
City
Sheffield
ZIP/Postal Code
S10 2SJ
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Facility Name
The Royal Marsden NHS Foundation Trust
City
Sutton
Country
United Kingdom
Facility Name
Singleton Hospital
City
Swansea
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
31902458
Citation
Simoes R, Miles E, Yang H, Le Grange F, Bhat R, Forsyth S, Seddon B. IMRiS phase II study of IMRT in limb sarcomas: Results of the pre-trial QA facility questionnaire and workshop. Radiography (Lond). 2020 Feb;26(1):71-75. doi: 10.1016/j.radi.2019.08.006. Epub 2019 Sep 14.
Results Reference
derived

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A Study of IMRT in Primary Bone and Soft Tissue Sarcoma

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