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

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ClinicalTrials.gov Identifier: NCT02520128
Recruitment Status : Recruiting
First Posted : August 11, 2015
Last Update Posted : October 20, 2017
Sponsor:
Collaborators:
Cancer Research UK
NCRI Radiotherapy Trials QA (RTTQA) Group
Information provided by (Responsible Party):
University College, London

Tracking Information
First Submitted Date  ICMJE July 31, 2015
First Posted Date  ICMJE August 11, 2015
Last Update Posted Date October 20, 2017
Study Start Date  ICMJE March 2016
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 13, 2017)
  • 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. [ Time Frame: From date of registration until 2 years after date of registration. ]
    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. [ Time Frame: Upon completion of IMRT treatment ]
    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. [ Time Frame: Upon completion of IMRT treatment ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 6, 2015)
  • 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. [ Time Frame: From date of registration until 2 years after date of registration ]
    Late toxicity assessment measured using RTOG late radiation morbidity criteria..
  • Cohorts 2 and 3 (Pelvic and spinal bone sarcomas): The proportion of patients where ≥95% of the recommended optimal RT dose can be achieved with IMRT [ Time Frame: Up to 4 weeks after registration ]
    The proportion of patients where ≥95% of the recommended optimal RT dose can be achieved with IMRT
Change History Complete list of historical versions of study NCT02520128 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2017)
  • Acute RT toxicity - (For all cohorts) [ Time Frame: From date of registration up to 90 days after date of registration ]
    In all 3 cohorts, Acute RT toxicity measured using RTOG acute radiation morbidity criteria.
  • Late RT toxicity - (For all cohorts) [ Time Frame: From Day 91 after date of registration up to 3 years after date of registration ]
    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) [ Time Frame: Timepoints- Baseline, 1 year and 2 year post treatment ]
    All cohorts, patient reported Quality of life measured using EORTC QLQ-C30 quality of life questionnaire
  • Patient reported limb function (Cohort 1 only) [ Time Frame: At timepoints - Baseline, 1 year and 2 years post Treatment ]
    For patients in Cohort 1 only, patient reported limb function measured using TESS questionnaire
  • Disease free survival (All Cohorts) [ 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 ]
    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) [ 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) ]
    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 Frame: From date of registration to date of documented recurrence within the irradiated site (assessed up to 3 years from date of registration) ]
    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 Frame: From date of registration to date of documented progression (assessed up to 3 years from date of registration) ]
    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) [ Time Frame: From date of registration to date of documented progression (assessed up to 3 years from date of registration) ]
    Response measured according to RECIST v 1.1 (for definitive radical RT)
  • Wound complications within 120 days of surgery (Cohort 1 only) [ Time Frame: From date of definitive surgery until 120 days post surgery ]
    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) [ Time Frame: Upon completion of IMRT treatment. ]
    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) [ Time Frame: Upon completion of IMRT treatment. ]
    Dose delivered to 95%, 80%, 70%, 60% and 50% volume of planPTV.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 6, 2015)
  • Acute RT toxicity - (For all cohorts) [ Time Frame: From date of registration up to 90 days after date of registration ]
    In all 3 cohorts, Acute RT toxicity measured using RTOG acute radiation morbidity criteria.
  • Late RT toxicity - (For all cohorts) [ Time Frame: From Day 91 after date of registration up to 3 years after date of registration ]
    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) [ Time Frame: Timepoints- Baseline, 1 year and 2 year post treatment ]
    All cohorts, patient reported Quality of life measured using EORTC QLQ-C30 quality of life questionnaire
  • Patient reported limb function (Cohort 1 only) [ Time Frame: At timepoints - Baseline, 1 year and 2 years post Treatment ]
    For patients in Cohort 1 only, patient reported limb function measured using TESS questionnaire
  • Disease free survival (All Cohorts) [ 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 ]
    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) [ 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) ]
    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 Frame: From date of registration to date of documented recurrence within the irradiated site (assessed up to 3 years from date of registration) ]
    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 Frame: From date of registration to date of documented progression (assessed up to 3 years from date of registration) ]
    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) [ Time Frame: From date of registration to date of documented progression (assessed up to 3 years from date of registration) ]
    Response measured according to RECIST v 1.1 (for definitive radical RT)
  • Wound complications within 120 days of surgery (Cohort 1 only) [ Time Frame: From date of definitive surgery until 120 days post surgery ]
    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.
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of IMRT in Primary Bone and Soft Tissue Sarcoma
Official Title  ICMJE A Phase II Study of Intensity Modulated Radiotherapy (IMRT) for Patients With Primary Bone and Soft Tissue Sarcoma
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.

Study Type  ICMJE Interventional
Study Phase Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Soft Tissue Sarcoma, Adult
  • Ewing Sarcoma
  • Bone Sarcoma
  • Chordoma
Intervention  ICMJE 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.
Study Arms
  • 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.
    Intervention: Radiation: Intensity modulated radiotherapy (IMRT)
  • 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.
    Intervention: Radiation: Intensity modulated radiotherapy (IMRT)
  • 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.
    Intervention: Radiation: Intensity modulated radiotherapy (IMRT)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 13, 2017)
200
Original Estimated Enrollment  ICMJE
 (submitted: August 6, 2015)
143
Estimated Study Completion Date March 2021
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender
Sexes Eligible for Study: All
Ages 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: Ihtisham Malik 020 7679 9281 ctc.imris@ucl.ac.uk
Listed Location Countries  ICMJE Ireland,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02520128
Other Study ID Numbers  ICMJE UCL/13/0376
C2921/A17558 ( Other Grant/Funding Number: Cancer Research UK )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party University College, London
Study Sponsor  ICMJE University College, London
Collaborators  ICMJE
  • Cancer Research UK
  • NCRI Radiotherapy Trials QA (RTTQA) Group
Investigators  ICMJE
Principal Investigator: Beatrice Seddon, Ph.D., M.D University College London Hospitals NHS Foundation Trust
PRS Account University College, London
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP