Validating predictive models and biomarkers of radiotherapy toxicity to reduce side effects and improve quality of life in cancer survivors
| ISRCTN | ISRCTN98496463 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN98496463 |
| Secondary identifying numbers | 601826 |
- Submission date
- 04/03/2014
- Registration date
- 19/03/2014
- Last edited
- 05/03/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Contact information
Prof Catharine West
Scientific
Scientific
Radiotherapy Related Research
University of Manchester
Christie Hospital
Wilmslow Road
Manchester
M20 4BX
United Kingdom
 ORCID ID |
0000-0002-0839-3449 |
|---|---|
| Phone | 0161 446 8275 |
| catharine.west@manchester.ac.uk |
Study information
| Study design | Prospective observational cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Quality of life |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Validating predictive models and biomarkers of radiotherapy toxicity to reduce side effects and improve quality of life in cancer survivors: a prospective observational cohort study |
| Study acronym | REQUITE |
| Study hypothesis | Primary objective: To establish a prospective cohort of patients undergoing radiotherapy for breast, prostate or lung cancer following local regimens and collecting standardised radiotherapy toxicity data, non-genetic risk factor data and samples for biomarker assays for the study of determinants of radiotherapy side-effects. Secondary objective: To establish a comprehensive centralised database and sample collection as a resource for the prospective evaluation and validation of clinical models incorporating biomarker data to identify before treatment those cancer patients who are at risk of developing long-term side effects from radiotherapy. |
| Ethics approval(s) | UK ethics approval obtained from North West - GM East REC, ref: 14 NW 0035 |
| Condition | Breast cancer, prostate cancer, lung cancer |
| Intervention | A pre-treatment blood sample will be collected from every patient at a single time point for downstream analyses. This sample comprises: Sample A: a whole blood EDTA sample for DNA extraction and either Sample B: a whole blood PAXgene sample for RNA extraction or Sample C: a whole blood Lithium Heparin sample for the apoptosis assay. Toxicity will be assessed and documented using REQUITE toxicity questionnaires based on the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 and EORTC Quality of Life. At some sites additional questionnaires will also be used: Multiple Fatigue Inventory (MFI) and the General Practice Assessment Questionnaire (GPAQ). Questionnaires will be completed at the following time points: 1. Baseline assessed prior to radiotherapy (all) 2. End of radiotherapy (breast and prostate); or first follow-up visit following implantation for prostate brachytherapy patients 3. 3 months from start of radiotherapy (lung) 4. 6 months from start of radiotherapy (lung) 5. 12 months from start of radiotherapy (all) 6. 24 months from start of radiotherapy (all) The follow-up period can be extended beyond 24 months. Further follow-up will be permissible and encouraged where possible as part of routine clinical care. |
| Intervention type | Other |
| Primary outcome measure | 1. Change in breast appearance at 24 months following start of radiotherapy (breast) measured by digital photograph 2. Rectal bleeding at 24 months following start of radiotherapy (prostate) measured by patient-reported outcome toxicity questionnaires 3. Dyspnea/breathlessness at 12 months following start of radiotherapy (lung) measured by patient-reported outcome toxicity questionnaires |
| Secondary outcome measures | 1. Other toxicity endpoints including but not limited to: fibrosis, induration and vascular changes (breast); rectal incontinence, urinary toxicity and erectile dysfunction (prostate); dysphagia and oesophagitis (lung) 2. Quality of life 3. Maximum grade of toxicity during follow-up period Toxicity will be assessed and documented using REQUITE toxicity questionnaires based on the CTCAE v4.0 and EORTC Quality of Life at the following time points. 1. Baseline assessed prior to radiotherapy (all) 2. End of radiotherapy (breast and prostate); or first follow-up visit following implantation for prostate brachytherapy patients 3. 3 months from start of radiotherapy (lung) 4. 6 months from start of radiotherapy (lung) 5. 12 months from start of radiotherapy (all) 6. 24 months from start of radiotherapy (all) |
| Overall study start date | 01/04/2014 |
| Overall study end date | 31/03/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 4439 |
| Total final enrolment | 4439 |
| Participant inclusion criteria | 1. Patients suitable for adjuvant radiotherapy* for cancer of the breast (invasive or in situ) including breast patients receiving neo-adjuvant chemotherapy 2. Patients suitable for radical radiotherapy or brachytherapy for prostate cancer; including post-prostatectomy patients 3. Patients suitable for radical radiotherapy, sequential or concurrent chemoradiotherapy or stereotactic body radiation therapy for lung cancer 4. No other malignancy prior to treatment for the specified tumour types except basal cell or squamous cell carcinoma of the skin 5. No evidence of distant metastases 6. Patients able to provide a venous blood sample 7. Willingness and ability to comply with scheduled visits, treatment plans and available for follow-up within country of origin 8. Greater than 18 years of age; no upper age limit 9. The capacity to understand the patient information sheet and the ability to provide written informed consent *Breast patients receiving chemotherapy should have completed their course of chemotherapy (anthracyclines) at least one month prior to radiotherapy commencing. |
| Participant exclusion criteria | 1. Patients with metastatic disease 2. Prior irradiation at the same site 3. Planned use of protons 4. Breast patients receiving concomitant chemo-radiation 5. Male breast cancer patients 6. Mastectomy patients 7. Bilateral breast cancer 8. Small cell lung cancer 9. Mental disability or patient otherwise unable to give informed consent and/or complete patient questionnaires 10. Limited life expectancy due to co-morbidity 11. Pregnant patients 12. Partial breast irradiation 13. Patients with breast implants if not removed during surgery 14. Patients with known HIV infection/infectious hepatitis |
| Recruitment start date | 01/04/2014 |
| Recruitment end date | 31/03/2018 |
Locations
Countries of recruitment
- Belgium
- England
- France
- Germany
- Italy
- Netherlands
- Spain
- United Kingdom
- United States of America
Study participating centres
Radiotherapy Related Research
Manchester
M20 4BX
United Kingdom
M20 4BX
United Kingdom
Centre d'imagerie de l'ICM Val d'Aurelle - Groupe CRP
Institut du Cancer
31 rue Croix Verte
Montpellier
34000
France
31 rue Croix Verte
Montpellier
34000
France
MAASTRO clinic
Doctor Tanslaan 12
Maastricht
6229 ET
Netherlands
Maastricht
6229 ET
Netherlands
Icahn School of Medicine at Mount Sinai
1 Gustave L. Levy Place
New York
10029
United States of America
New York
10029
United States of America
The Christie NHS Foundation Trust
Wilmslow Road
Manchester
M20 4BX
United Kingdom
Manchester
M20 4BX
United Kingdom
Fundación Publica Galega Medicina Xenomica
CHUS Edif Consultas, floor -2
Choupana s/n
Santiago de Compostela
15706
Spain
Choupana s/n
Santiago de Compostela
15706
Spain
Fondazione IRCCS Istituto Nazionale dei Tumori
Via Giacomo Venezian, 1
Milan
20133
Italy
Milan
20133
Italy
University Hospital Leuven
Herestraat 49
Leuven
3000
Belgium
Leuven
3000
Belgium
Universitair Ziekenhuis Gent
Corneel Heymanslaan 10
Ghent
9000
Belgium
Ghent
9000
Belgium
Universitaet Mannheim
Mannheim
68131
Germany
68131
Germany
Fundació Privada Institut d'Investigació Oncológica Vall d'Hebron
Centro Cellex
Calle Natzaret
115-117
Barcelona
08035
Spain
Calle Natzaret
115-117
Barcelona
08035
Spain
University Hospitals of Leicester
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Leicester
LE1 5WW
United Kingdom
Städtisches Klinikum Karlsruhe
Moltkestraße 90
Karlsruhe
76133
Germany
Karlsruhe
76133
Germany
St. Vincentius-Kliniken gAG Karlsruhe
Steinhäuserstraße 18
Karlsruhe
76137
Germany
Karlsruhe
76137
Germany
Klinikum der Stadt Ludwigshafen GmbH
Bremserstraße 79
Ludwigshafen am Rhein
67063
Germany
Ludwigshafen am Rhein
67063
Germany
Praxis Strahlentherapie
Paul-Egell-Straße 31
Speyer
67346
Germany
Speyer
67346
Germany
Zentrum für Strahlentherapie
Wirthstraße 11c
Freiburg im Breisgau
79110
Germany
Freiburg im Breisgau
79110
Germany
Klinikum Darmstadt
Grafenstraße 9
Darmstadt
64283
Germany
Darmstadt
64283
Germany
Strahlentherapie An der Stadtklinik
Balger Str. 50
Baden-Baden
76532
Germany
Baden-Baden
76532
Germany
The Institute for Cancer Research and Treatment
Strada Provinciale
Candiolo
10060
Italy
Candiolo
10060
Italy
Derby Hospitals NHS Foundation Trust
Uttoxeter Road
Derby
DE22 3NE
United Kingdom
Derby
DE22 3NE
United Kingdom
Nottingham University Hospitals NHS Trust
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
Nottingham
NG5 1PB
United Kingdom
Salford Royal Foundation Trust
Stott Lane
Salford
M6 8HD
United Kingdom
Salford
M6 8HD
United Kingdom
Birmingham NHS Foundation Trust
Birmingham
B15 2TH
United Kingdom
B15 2TH
United Kingdom
Centre Hospitalier Régional Universitaire de Nîmes
4 Rue du Professeur Robert Debré
Nîmes
30029
France
Nîmes
30029
France
Memorial Sloan Kettering Cancer Centre
1275 York Ave
New York
10065
United States of America
New York
10065
United States of America
Queens Cancer Centre
82-68 164th Street New-Bldg
5th Floor
Jamaica
New York
11432
United States of America
5th Floor
Jamaica
New York
11432
United States of America
Sponsor information
University of Manchester (UK)
University/education
University/education
c/o Lynne MacRae
Faculty of Biology, Medicine and Health
The University of Manchester
Room 1.21a Simon Building
Brunswick Street
Manchester
M13 9PL
England
United Kingdom
| Phone | +44 161 275 5436 |
|---|---|
| research-governance@manchester.ac.uk | |
"ROR" |
https://ror.org/027m9bs27 |
Funders
Funder type
Government
European Union - Seventh Framework Programme for Research, Technological Development and Demonstration, Ref. 601826
No information available
Results and Publications
| Intention to publish date | 30/09/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | |
| IPD sharing plan | We have an extensive resource of treatment, toxicity & PRO data as well as DVH & DICOM, genotyping & breast photos. It is accessible to all (following submission and approval of a concept form). Researchers can find out top level data on numbers of patients with particular characteristics using our ‘Data Discovery’ link off the website. Our CRFs are available on the website for use by others to improve standardisation of data collection in the field. A baseline manuscript is in preparation describing the cohort in detail. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Plain English results | No | Yes | |||
| Results article | results | 01/09/2019 | 05/03/2020 | Yes | No |
Editorial Notes
05/03/2020: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
29/11/2018: Cancer Research UK lay results summary link added to Results (plain English).
13/08/2018: ICM-Val d'Aurelle, MAASTRO clinic, Icahn School of Medicine at Mount Sinai, The Christie NHS Foundation Trust, Fundación Publica Galega Medicina Xenomica, Fondazione IRCCS Instituto Nazionale dei Tumori, University Hospital Leuven, Universitair Ziekenhuis Gent, Universitaet Mannheim, Fundació Privada Institut d'Investigació Oncológica Vall d'Hebron, University Hospitals of Leicester NHS Foundation Trust, Städtisches Klinikum Karlsruhe, St. Vincentius-Kliniken gAG, Klinkikum der Stadt Ludwigshafen GmbH, Praxis Strahlentherapie, Zentrum für Strahlentherapie Freiburg,b Klinikum Darmstadt GmbH, Strahlentherapie An der Stadtklinik, The Institute for Cancer Research and Treatment, Derby Hospitals NHS Foundation Trust, Nottingham University Hospitals NHS Trust, Salford Royal Foundation Trust, Birmingham NHS Foundation Trust, Centre Hospitalier Régional Universitaire de Nîmes, Memorial Sloan Kettering Cancer Centre, and Queens Cancer Centre were added as trial participating centres.
09/08/2018: The following changes were made to the trial record:
1. ORCID ID and telephone number added to contact details
2. Telephone number and address updated for sponsor
3. The overall trial end date was changed from 31/03/2018 to 31/09/2019
4. The target number of participants was changed from 5300 to 4439
5. The total target enrolment was changed from 5300 to 4439
6. The Netherlands was added as a country of recruitment.
7. Participant level data was changed from "not provided at time of registration" to "available on request"
8. The publication and dissemination plan was updated
9. The intention to publish date was added.
