A Study of IMRT in Primary Bone and Soft Tissue Sarcoma

NCT ID: NCT02520128

Last Updated: 2020-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

191 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-31

Study Completion Date

2020-06-30

Brief Summary

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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

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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.

Conditions

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Soft Tissue Sarcoma, Adult Ewing Sarcoma Bone Sarcoma Chordoma

Keywords

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Intensity Modulated Radiotherapy Radiotherapy

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1 (closed to recruitment)

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.

Group Type OTHER

Intensity modulated radiotherapy (IMRT)

Intervention Type RADIATION

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.

Cohort 2

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.

Group Type OTHER

Intensity modulated radiotherapy (IMRT)

Intervention Type RADIATION

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.

Cohort 3

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.

Group Type OTHER

Intensity modulated radiotherapy (IMRT)

Intervention Type RADIATION

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.

Interventions

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Intensity modulated radiotherapy (IMRT)

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.

Intervention Type RADIATION

Eligibility Criteria

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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.
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cancer Research UK

OTHER

Sponsor Role collaborator

NCRI Radiotherapy Trials QA (RTTQA) Group

UNKNOWN

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Beatrice Seddon, Ph.D., M.D

Role: PRINCIPAL_INVESTIGATOR

University College London Hospitals

Locations

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St Luke's Hospital

Dublin, , Ireland

Site Status

Clatterbridge Cancer Centre

Bebington, , United Kingdom

Site Status

Belfast City Hospital

Belfast, , United Kingdom

Site Status

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Site Status

Bristol Haematology and Oncology Centre

Bristol, , United Kingdom

Site Status

Adenbrookes' Hospital

Cambridge, , United Kingdom

Site Status

Velindre Hospital

Cardiff, , United Kingdom

Site Status

Cheltenham Hospital

Cheltenham, , United Kingdom

Site Status

University Hospital Coventry

Coventry, , United Kingdom

Site Status

Royal Derby Hospital

Derby, , United Kingdom

Site Status

Western General Hospital

Edinburgh, , United Kingdom

Site Status

Royal Devon & Exeter Foundation Trust

Exeter, , United Kingdom

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

St James' Institute of Oncology

Leeds, , United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, , United Kingdom

Site Status

University College London Hospitals

London, , United Kingdom

Site Status

The Christie Hospital

Manchester, , United Kingdom

Site Status

Northern Centre for Cancer Care

Newcastle, , United Kingdom

Site Status

Northampton General Hospital

Northampton, , United Kingdom

Site Status

Norfolk and Norwich University Hospital

Norwich, , United Kingdom

Site Status

Nottingham City Hospital

Nottingham, , United Kingdom

Site Status

Churchill Hospital

Oxford, , United Kingdom

Site Status

Derriford Hospital

Plymouth, , United Kingdom

Site Status

Royal Preston Hospital

Preston, , United Kingdom

Site Status

Weston Park Hospital

Sheffield, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust

Sutton, , United Kingdom

Site Status

Singleton Hospital

Swansea, , United Kingdom

Site Status

Countries

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Ireland United Kingdom

References

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Simoes R, Gulliford S, Seddon B, Dehbi HM, Robinson M, Forsyth S, Hughes A, Gaunt P, Nguyen TG, Elston S, Mohammed K, Zaidi S, Miles E, Hoskin P, Harrington K, Miah A. Predicting radiotherapy response, Toxicities and quality-of-life related functional outcomes in soft tissue sarcoma of the extremities (PredicT) using dose-volume constraints development: a study protocol. BMJ Open. 2024 Aug 9;14(8):e083617. doi: 10.1136/bmjopen-2023-083617.

Reference Type DERIVED
PMID: 39122389 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31902458 (View on PubMed)

Other Identifiers

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C2921/A17558

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

UCL/13/0376

Identifier Type: -

Identifier Source: org_study_id