Clinical trial NCT02520128: A Study of IMRT in Primary Bone and Soft Tissue Sarcoma
Official title: A Phase II Study of Intensity Modulated Radiotherapy (IMRT) for Patients With Primary Bone and Soft Tissue Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Soft Tissue Sarcoma, Adult
Ewing Sarcoma
Bone Sarcoma
Chordoma
Keywords: Intensity Modulated Radiotherapy
Radiotherapy
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
name: NCRI Radiotherapy Trials QA (RTTQA) Group
First posted: 2015-08-11
Enrollment: 191
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: From date of registration until 2 years after date of registration.
measure: 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.
timeFrame: Upon completion of IMRT treatment
measure: 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.
timeFrame: Upon completion of IMRT treatment
Secondary outcomes:
measure: Acute RT toxicity - (For all cohorts)
timeFrame: From date of registration up to 90 days after date of registration
measure: Late RT toxicity - (For all cohorts)
timeFrame: From Day 91 after date of registration up to 3 years after date of registration
measure: Patient reported Quality of life (QOL) - (All cohorts)
timeFrame: Timepoints- Baseline, 1 year and 2 year post treatment
measure: Patient reported limb function (Cohort 1 only)
timeFrame: At timepoints - Baseline, 1 year and 2 years post Treatment
measure: Disease free survival (All Cohorts)
timeFrame: 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
measure: Overall survival (All Cohorts)
timeFrame: From date of registration to date of death or date of last follow-up assessment (assessed up to 3 years from date of registration)
measure: Time to local tumour recurrence (All Cohorts, for adjuvant RT)
timeFrame: From date of registration to date of documented recurrence within the irradiated site (assessed up to 3 years from date of registration)
measure: Time to local disease progression (Cohorts 2 and 3, for definitive radical RT)
timeFrame: From date of registration to date of documented progression (assessed up to 3 years from date of registration)
measure: Response by RECIST 1.1 (Cohorts 2 and 3, for definitive radical RT)
timeFrame: From date of registration to date of documented progression (assessed up to 3 years from date of registration)
measure: Wound complications within 120 days of surgery (Cohort 1 only)
timeFrame: From date of definitive surgery until 120 days post surgery
measure: For individual plans (cohort 2 & 3)
timeFrame: Upon completion of IMRT treatment.
measure: For individual plans (cohort 2 & 3)
timeFrame: Upon completion of IMRT treatment.
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: St Luke's Hospital
city: Bebington
country: United Kingdom
facility: Clatterbridge Cancer Centre
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: Cambridge
country: United Kingdom
facility: Adenbrookes' Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Hospital
city: Cheltenham
country: United Kingdom
facility: Cheltenham Hospital
city: Coventry
country: United Kingdom
facility: University Hospital Coventry
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon & Exeter Foundation Trust
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Leeds
country: United Kingdom
facility: St James' Institute of Oncology
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: University College London Hospitals
city: Manchester
country: United Kingdom
facility: The Christie Hospital
city: Newcastle
country: United Kingdom
facility: Northern Centre for Cancer Care
city: Northampton
country: United Kingdom
facility: Northampton General Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Swansea
country: United Kingdom
facility: Singleton Hospital
Study officials:
affiliation: University College London Hospitals
name: Beatrice Seddon, Ph.D., M.D
role: PRINCIPAL_INVESTIGATOR
References:
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.