Soft Tissue Sarcoma of the ExtremitiesPredicT-BNCT05978024
Predicting Radiotherapy Response and Toxicities in Soft Tissue Sarcoma of the Extremities - Cohort B
An observational study of Soft Tissue Sarcoma of the Extremities, run by Royal Marsden NHS Foundation Trust at 3 sites in United Kingdom.
Trial summary
This is a multicentre prospective cohort study, primarily aimed at reporting the frequency and intensity of radiotherapy side-effects of patients with soft tissues sarcoma of the extremities (STSE). Read more about this study
- Who is it for?
- Ages 16 years and olderHealthy volunteers can take part
- Conditions the study is for
- Soft Tissue Sarcoma of the Extremities
- How many people
- 150 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 16 Apr 2021to 30 Jul 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: The study population to be enrolled in this observational study will have had been diagnosed with STSE and referred to receive a course of radiotherapy either in the primary, palliative, pre-operative or post-operative settings.
Who may be able to join
- Histopathological diagnosis of soft tissue sarcoma of the upper or lower limb or limb girdle;
- Patients receiving pre-operative (neo-adjuvant), post-operative (adjuvant) or palliative radiotherapy;
- Patients receiving radiotherapy planned as per local protocols (neoadjuvant chemotherapy will be allowed). Neoadjuvant chemotherapy patients may be approached as they commence chemotherapy;
- WHO performance status 0-2;
- Aged ≥16 years;
- Patients fit enough to undergo radiotherapy treatment and willing to attend follow up visits, during two years;
- 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.
Who cannot join
- Previous radiotherapy to the same site;
- Pregnancy;
- Patients with concurrent or previous malignancy that could compromise assessment of primary and secondary endpoints of the trial.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites, 3 recruiting
- Recruiting
Addenbrooke's Hospital
Cambridge, CB2 0QQ
Katy Cooper
Sarah Prewett
- Recruiting
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
Thuy-Giang Nguyen, +442078118090, Thuy-Giang.Nguyen@rmh.nhs.uk
Aisha Miah
- Recruiting
University College London
London, WC1E 6BT
Carla Dalton
Mahbubl Ahmed
About this study
Official title: Predicting Radiotherapy Response, Toxicities and Quality of Life Related Functional Outcome in Soft Tissue Sarcoma of the Extremities: a Prospective Observational Cohort Study
This is a multicentre prospective cohort study, primarily aimed at reporting the frequency and intensity of radiotherapy side-effects of patients with soft tissues sarcoma of the extremities (STSE).
Two sub-studies are proposed within this study:
Read more
- MRI radiation response assessment Aimed at establishing whether changes in median apparent diffusion coefficients (ADC) are predictive of pre-operative STSE response measured using histopathology.
- Biomarker development and Immune mediators associated with radiotherapy Aimed at establishing prognostic markers which may refine selection of cases for pre-operative, palliative or no radiotherapy.
Also, aimed at determining if radiotherapy stimulates the tumour microenvironment, resulting in measurable change in anti-tumour immunity and if certain subtypes could potentially benefit from the addition of immunotherapy with radiation.
Patients participation in the sub-studies is optional.
Read the detailed description
This is a multicentre prospective cohort study, primarily aimed at validating the dose-volume parameters identified in the analyses of the VorteX and IMRiS trials datasets.
- Delineation of healthy tissues
Pre-defined outlining guidelines of normal tissues as bones, muscle compartments, joints, lymph drainage basins and subcutaneous tissue from Predict A will be delineated in radiotherapy planning computed tomography (CT) images. All cases will be delineated by a single observer (Rita Simoes). Verification of all outlines will be carried out by Dr Aisha Miah (clinical supervisor).
- Dose-volume constraints validity testing
Patients will be treated as per local protocol treatment technique.
Radiotherapy, clinical and toxicities data will be collected, with no new intervention on the treatment. Patients enrolled will receive standard radiation prescription doses as described below:
- Pre-operative radiotherapy- 50 Gy in 25 fractions equivalent (pre-operative radiotherapy). Where appropriate hypo-fractionated schedules as per institutional guidelines can considered: eg. 25 Gy/ 5 daily fractions. In myxoid liposarcomas, 36 Gy in 18 fractions can be considered where suitable;
- Post-operative radiotherapy- 60 Gy in 30 fractions or 66 Gy in 33 fractions (positive resection margins); alternative hypo-fractionated schedules as per institutional guidelines can be considered;
- Palliative radiotherapy- 30-36 Gy in 10-12 daily fractions, 40-45 Gy in 15 fractions, 30-36 Gy in 5-6 once weekly fractions or 25 Gy in 5 daily fractions.
Toxicity will be assessed with the TESS and RTOG scoring instruments and Stern score for lymphoedema. Patients enrolled in the study will fill in a specific quality-of-life questionnaire to assess quality of life related functional outcomes following treatment for STSE. This questionnaire is based on validated questions for assessing quality-of-life. Patients will be followed up at 3, 6, 12, 18, and 24 months post-radiotherapy.
- Conditions
- Soft Tissue Sarcoma of the Extremities
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of any RTOG grade ≥ 2 toxicities following treatment for STSE at 24 months
The primary objective is to report the frequency and intensity of radiotherapy side-effects in STSE.
Measured: 24 Months
Secondary outcomes (7)
The ability of the fitted model from dose-volume constraints from PredicT A (IMRiS and Vortex analysis) to correctly predict the incidence of grade 2+ among PredicT B patients.
To report the differences in experienced by patients with STSE for whom dose-volume constraints were below or exceeded. Binary logistic regression will be used to quantify the differences using odds ratios (OR) from the fitted models. Univariate logistic regression models will be fitted to predict for the parameters relevant to toxicity grades in the RTOG, Stern's and TESS scales. ORs for each of the parameters will be used to judge for significant differences between the groups. There is no plan to fit multivariate model.
Measured: 24 Months
To report frequencies and proportions of radiotherapy-induced late toxicities
Frequencies and proportions of radiotherapy-induced late toxicities at the specified at 3, 6, 12, 18 and 24 months will be reported descriptively at each time point for the overall events and by types of events:
- Subcutaneous tissue fibrosis
- Lymphoedema
- Bone fractures
- Joint stiffness
- Delayed wound healing following pre-operative RT
Measured: 24 Months
To determine the time to developing early and late side-effects.
Time elapsed between day 1 of radiotherapy and the day to develop early and late side-effects using Kaplan-Meier methods. Median time to early side-effects with 95% confidence interval will be reported. Patients without any side-effects (on day 90 from end of RT) will be censored. Similarly, median time to late side-effects with 95% confidence interval will be reported. Patients without an event will be censored at the 24 months assessment visit or at last follow-up date known to be on the study without any event.
Measured: 24 Months
To determine radiological response rates to radiotherapy and where applicable chemo-radiotherapy for STSE of different histological subtypes.
Differences in the tumour volumes (in cc and %) will be calculated from CT and CBCT images at fractions 8, 16 and 25 for patients receiving pre-operative RT. Changes in target volumes during radiotherapy will be assessed by computing dissimilarity indices (e.g., Simpson's dissimilarity index) in sequential CBCT images captured during treatment compared to radiotherapy planning CT. Radiological: % volume change (RECIST), % cystic sold component).
Measured: 24 Months
To determine histological response rates to radiotherapy and where applicable chemo-radiotherapy for STSE of different histological subtypes.
Differences in the response rates will be assessed according to: histopathological semi-quantitative scores (pathological: % viable cells). Tumour factors are tumour histotype, staging and tumour size.
Measured: 24 Months
To determine quality of life-related functional outcomes and explore correlations with dose-volume parameters for patients who have received pre, post-operative or palliative radiotherapy for STSE.
Correlations between functional outcomes (expressed in TESS and EORT-QLQ- C30 and QLQ-FA12 fatigue questionnaire scores) with dose-volume parameters (expressed in Gy/volume, where volume will be defined in % of total volume and cc) will be calculated using Spearman's correlation method. Patients will be categorised according to dose volume constraints and compare the groups using t-test or Mann-Whitney non-parametric test as appropriate.
Measured: 24 Months
To determine predictive and prognostic factors for local and distant recurrence and overall survival for patients receiving pre-operative and palliative RT.
Percentage of patients responding to treatment will be calculated, this will be reported in the overall patients and for dose-volume constraints groups. Local control rates, disease-free survival rates and overall survival at 2 years will be calculated using Kaplan-Meier methods. Disease free survival events are local or distance disease recurrence and death from disease related causes. Overall survival events are death from any causes.
Measured: 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2023
- Study start16 Apr 2021
- Primary completion30 Jul 2024 (estimated)
- Study completion30 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Soft Tissue Sarcoma of the ExtremitiesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Aisha Miah, Principal investigator, The Royal Marsden Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05978024
- Sponsor's protocol ID
- CCR5166
- Acronym
- PredicT-B
- Status last verified
- Jul 2023
- First submitted
- 14 Jul 2023
- Last updated
- 7 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Patient outcomes data will be utilised to publish study endpoints. However specific participant data will not be shared. We aim to publish protocol, and study results in the form of peer-reviewed publications and guidelines
Publications
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.
PubMed 39122389
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predicting Radiotherapy Response, Toxicities and Quality of Life Related Functional Outcome in Soft Tissue Sarcoma of the Extremities: a Prospective Observational Cohort Study
- ClinicalTrials.gov ID
- NCT05978024
- Acronym / sponsor ID
- PredicT-B / CCR5166
- Conditions
- Soft Tissue Sarcoma of the Extremities
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Study start
- 16 Apr 2021 (actual)
- Primary completion
- 30 Jul 2024 (estimated)
- Study completion
- 30 Jul 2026 (estimated)
- First posted
- 7 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicentre prospective cohort study, primarily aimed at reporting the frequency and intensity of radiotherapy side-effects of patients with soft tissues sarcoma of the extremities (STSE).
Two sub-studies are proposed within this study:
- MRI radiation response assessment Aimed at establishing whether changes in median apparent diffusion coefficients (ADC) are predictive of pre-operative STSE response measured using histopathology.
- Biomarker development and Immune mediators associated with radiotherapy Aimed at establishing prognostic markers which may refine selection of cases for pre-operative, palliative or no radiotherapy.
Also, aimed at determining if radiotherapy stimulates the tumour microenvironment, resulting in measurable change in anti-tumour immunity and if certain subtypes could potentially benefit from the addition of immunotherapy with radiation.
Patients participation in the sub-studies is optional.
Detailed description
This is a multicentre prospective cohort study, primarily aimed at validating the dose-volume parameters identified in the analyses of the VorteX and IMRiS trials datasets.
- Delineation of healthy tissues
Pre-defined outlining guidelines of normal tissues as bones, muscle compartments, joints, lymph drainage basins and subcutaneous tissue from Predict A will be delineated in radiotherapy planning computed tomography (CT) images. All cases will be delineated by a single observer (Rita Simoes). Verification of all outlines will be carried out by Dr Aisha Miah (clinical supervisor).
- Dose-volume constraints validity testing
Patients will be treated as per local protocol treatment technique.
Radiotherapy, clinical and toxicities data will be collected, with no new intervention on the treatment. Patients enrolled will receive standard radiation prescription doses as described below:
- Pre-operative radiotherapy- 50 Gy in 25 fractions equivalent (pre-operative radiotherapy). Where appropriate hypo-fractionated schedules as per institutional guidelines can considered: eg. 25 Gy/ 5 daily fractions. In myxoid liposarcomas, 36 Gy in 18 fractions can be considered where suitable;
- Post-operative radiotherapy- 60 Gy in 30 fractions or 66 Gy in 33 fractions (positive resection margins); alternative hypo-fractionated schedules as per institutional guidelines can be considered;
- Palliative radiotherapy- 30-36 Gy in 10-12 daily fractions, 40-45 Gy in 15 fractions, 30-36 Gy in 5-6 once weekly fractions or 25 Gy in 5 daily fractions.
Toxicity will be assessed with the TESS and RTOG scoring instruments and Stern score for lymphoedema. Patients enrolled in the study will fill in a specific quality-of-life questionnaire to assess quality of life related functional outcomes following treatment for STSE. This questionnaire is based on validated questions for assessing quality-of-life. Patients will be followed up at 3, 6, 12, 18, and 24 months post-radiotherapy.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study population to be enrolled in this observational study will have had been diagnosed with STSE and referred to receive a course of radiotherapy either in the primary, palliative, pre-operative or post-operative settings.
Key inclusion criteria (8 listed)
- Histopathological diagnosis of soft tissue sarcoma of the upper or lower limb or limb girdle;
- Patients receiving pre-operative (neo-adjuvant), post-operative (adjuvant) or palliative radiotherapy;
- Patients receiving radiotherapy planned as per local protocols (neoadjuvant chemotherapy will be allowed). Neoadjuvant chemotherapy patients may be approached as they commence chemotherapy;
- WHO performance status 0-2;
- Aged ≥16 years;
Key exclusion criteria (3 listed)
- Previous radiotherapy to the same site;
- Pregnancy;
- Patients with concurrent or previous malignancy that could compromise assessment of primary and secondary endpoints of the trial.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The incidence of any RTOG grade ≥ 2 toxicities following treatment for STSE at 24 months
Time frame: 24 Months
The primary objective is to report the frequency and intensity of radiotherapy side-effects in STSE.
7 secondary outcomes
The ability of the fitted model from dose-volume constraints from PredicT A (IMRiS and Vortex analysis) to correctly predict the incidence of grade 2+ among PredicT B patients.
Time frame: 24 Months
To report frequencies and proportions of radiotherapy-induced late toxicities
Time frame: 24 Months
To determine the time to developing early and late side-effects.
Time frame: 24 Months
To determine radiological response rates to radiotherapy and where applicable chemo-radiotherapy for STSE of different histological subtypes.
Time frame: 24 Months
To determine histological response rates to radiotherapy and where applicable chemo-radiotherapy for STSE of different histological subtypes.
Time frame: 24 Months
To determine quality of life-related functional outcomes and explore correlations with dose-volume parameters for patients who have received pre, post-operative or palliative radiotherapy for STSE.
Time frame: 24 Months
To determine predictive and prognostic factors for local and distant recurrence and overall survival for patients receiving pre-operative and palliative RT.
Time frame: 24 Months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2023.
- Derived from this study: PubMed 39122389Simoes 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.
- Individual participant dataSharing planned: No. Patient outcomes data will be utilised to publish study endpoints. However specific participant data will not be shared. We aim to publish protocol, and study results in the form of peer-reviewed publications and guidelines
Related trials for Soft Tissue Sarcoma of the Extremities
RecruitingPhase 3
Measuring if Immunotherapy Plus Chemotherapy is Better Than Chemotherapy Alone for Patients With Aggressive Poorly Differentiated Sarcomas
Metastatic Dedifferentiated Liposarcoma, Metastatic Undifferentiated Pleomorphic Sarcoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Abemaciclib, to the Usual Chemotherapy Treatment (Gemcitabine) for Soft Tissue Sarcoma
Advanced Dedifferentiated Liposarcoma, Advanced Leiomyosarcoma
Active, not recruitingPhase 2
Testing the Addition of Cemiplimab to Palbociclib for the Treatment of Advanced Dedifferentiated Liposarcoma
Advanced Dedifferentiated Liposarcoma, Locally Advanced Dedifferentiated Liposarcoma
RecruitingPhase 3
Testing Short-Course Radiation Versus Standard-Course Radiation for Soft Tissue Sarcomas That Need Surgery and Radiation
Recurrent Soft Tissue Sarcoma of the Trunk and Extremities, Resectable Soft Tissue Sarcoma of the Trunk and Extremities
Active, not recruitingPhase 2
Talimogene Laherparepvec and Radiation Therapy in Treating Patients With Newly Diagnosed Soft Tissue Sarcoma That Can Be Removed by Surgery
Leiomyosarcoma, Liposarcoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aisha Miah principal investigator
The Royal Marsden Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Soft Tissue Sarcoma of the Extremities, run by Royal Marsden NHS Foundation Trust at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Thuy-Giang Nguyen (02078118090, Thuy-Giang.Nguyen@rmh.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence of any RTOG grade ≥ 2 toxicities following treatment for STSE at 24 months (time frame: 24 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05978024, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2023.