A Study of IMRT in Primary Bone and Soft Tissue Sarcoma

Ewing Sarcoma Clinical Trial

— IMRiS  

Official title:

A Phase II Study of Intensity Modulated Radiotherapy (IMRT) for Patients With Primary Bone and Soft Tissue Sarcoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02520128
• Other study ID #: UCL/13/0376
• Secondary ID: C2921/A17558
• Status: Completed
• Phase: N/A
• Start date: March 2016
• Est. completion date: June 30, 2020

Study information

• Verified date: December 2020
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 191
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bone Sarcoma
• Chordoma
• Ewing Sarcoma
• Osteosarcoma
• Sarcoma
• Sarcoma, Ewing
• Soft Tissue Sarcoma, Adult

Intervention

Radiation:
• 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.

Locations

Country	Name	City	State
Ireland	St Luke's Hospital	Dublin
United Kingdom	Clatterbridge Cancer Centre	Bebington
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Adenbrookes' Hospital	Cambridge
United Kingdom	Velindre Hospital	Cardiff
United Kingdom	Cheltenham Hospital	Cheltenham
United Kingdom	University Hospital Coventry	Coventry
United Kingdom	Royal Derby Hospital	Derby
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Royal Devon & Exeter Foundation Trust	Exeter
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	St James' Institute of Oncology	Leeds
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	University College London Hospitals	London
United Kingdom	The Christie Hospital	Manchester
United Kingdom	Northern Centre for Cancer Care	Newcastle
United Kingdom	Northampton General Hospital	Northampton
United Kingdom	Norfolk and Norwich University Hospital	Norwich
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Royal Preston Hospital	Preston
United Kingdom	Weston Park Hospital	Sheffield
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton
United Kingdom	Singleton Hospital	Swansea

Sponsors (3)

Lead Sponsor	Collaborator
University College, London	Cancer Research UK, NCRI Radiotherapy Trials QA (RTTQA) Group

Countries where clinical trial is conducted

Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From date of registration until 2 years after date of registration.
Primary	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.	Upon completion of IMRT treatment
Primary	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.	Upon completion of IMRT treatment
Secondary	Acute RT toxicity - (For all cohorts)	In all 3 cohorts, Acute RT toxicity measured using RTOG acute radiation morbidity criteria.	From date of registration up to 90 days after date of registration
Secondary	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	From Day 91 after date of registration up to 3 years after date of registration
Secondary	Patient reported Quality of life (QOL) - (All cohorts)	All cohorts, patient reported Quality of life measured using EORTC QLQ-C30 quality of life questionnaire	Timepoints- Baseline, 1 year and 2 year post treatment
Secondary	Patient reported limb function (Cohort 1 only)	For patients in Cohort 1 only, patient reported limb function measured using TESS questionnaire	At timepoints - Baseline, 1 year and 2 years post Treatment
Secondary	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.	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
Secondary	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	From date of registration to date of death or date of last follow-up assessment (assessed up to 3 years from date of registration)
Secondary	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).	From date of registration to date of documented recurrence within the irradiated site (assessed up to 3 years from date of registration)
Secondary	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.	From date of registration to date of documented progression (assessed up to 3 years from date of registration)
Secondary	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)	From date of registration to date of documented progression (assessed up to 3 years from date of registration)
Secondary	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.	From date of definitive surgery until 120 days post surgery
Secondary	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)	Upon completion of IMRT treatment.
Secondary	For individual plans (cohort 2 & 3)	Dose delivered to 95%, 80%, 70%, 60% and 50% volume of planPTV.	Upon completion of IMRT treatment.