A study comparing three vs six cycles of platinum-based chemotherapy before avelumab in advanced bladder cancer
| ISRCTN | ISRCTN15750433 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15750433 |
| EudraCT/CTIS number | 2021-001975-17 |
| IRAS number | 1003775 |
| Secondary identifying numbers | CPMS 50666, IRAS 1003775 |
- Submission date
- 21/02/2022
- Registration date
- 10/03/2022
- Last edited
- 29/01/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English Summary
Background and study aims
Urothelial carcinoma is a type of bladder cancer where cancer cells develop from the cells of the bladder lining. Urothelial carcinoma can become invasive which means that it has grown into a deeper layer of the bladder. Urothelial carcinoma can also spread to other parts of the body distant from the bladder (metastatic). Currently, the best treatment for bladder cancer is to receive combination chemotherapy for up to six cycles, followed by maintenance immunotherapy (avelumab). This study aims to determine if receiving three cycles of combination chemotherapy followed by maintenance avelumab results in a better quality of life for patients whilst maintaining the same level of effectiveness.
Who can participate?
Patients aged 18 years and over with histologically confirmed, unresectable (can't be surgically removed) locally advanced or metastatic urothelial carcinoma. Various other inclusion criteria must be met to take part
What does the study involve?
If eligible, participants will receive one of two possible treatments: gemcitabine plus cisplatin/carboplatin for three cycles, followed by maintenance avelumab for up to 2 years from the end of chemotherapy OR gemcitabine plus cisplatin/carboplatin for six cycles, followed by maintenance avelumab for up to 2 years from the end of chemotherapy. The number of study procedures such as CT/MRI scans and the maximum amount of blood samples taken will vary depending on how many cycles of treatment are received. Patients will complete quality of life questionnaires at various time points throughout the study.
What are the possible benefits and risks of participating?
This study aims to find out information that may help people with bladder cancer. The researchers cannot guarantee that there will be a benefit to participants during treatment as this is unknown at this stage. This study is in line with the standard of care treatment, using drugs that are licensed for use in the UK. The full summary of the risks of taking part will be explained by the treating physician before participants consent to the study.
Where is the study run from?
The Barts ECMC, Centre for Experiment Cancer Medicine, Queen Mary University of London (UK)
When is the study starting and how long is it expected to run for?
January 2021 to October 2026
Who is funding the study?
Merck Healthcare KGaA (Germany)
Who is the main contact?
Prof. Thomas Powles
bci-discus@qmul.ac.uk
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-3-cycles-of-chemotherapy-for-urothelial-cancer-urinary-tract-cancer-discus
Contact information
Scientific
Barts ECMC
Centre for Experimental Cancer Medicine
Barts Cancer Institute
Old Anatomy Building
Charterhouse Square
London
EC1M 6BQ
United Kingdom
| Phone | +44 (0)20 7882 8490 |
|---|---|
| bci-discus@qmul.ac.uk |
Study information
| Study design | Interventional; Randomized; Design type: Treatment, Drug, Immunotherapy |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | A randomised Phase II study comparing three vs six cycles of platinum-based chemotherapy prior to maintenance avelumab in advanced urothelial cancer (DISCUS) |
| Study acronym | DISCUS |
| Study hypothesis | Three cycles of platinum-based chemotherapy will be at least as active as the current standard approach of six cycles, followed by maintenance avelumab. |
| Ethics approval(s) | Approved 28/10/2021, London – Riverside Research Ethics Committee (Ground Floor, Temple Quay House, 2 The Square, Bristol, BS1 6PN, UK; +44 (0)207 104 8193, +44 (0)207 104 8184; riverside.rec@hra.nhs.uk), REC ref: 21/LO/0694 |
| Condition | Bladder cancer |
| Intervention | Eligible patients will be randomised in a 1:1 ratio using the minimisation method to receive either: Arm A: three cycles of Q3W gemcitabine (1000 mg/m²) + carboplatin (AUC 4.5 or 5, as per local practice) / cisplatin (70 mg/m²) followed by maintenance avelumab (800 mg Q2W) Arm B: six cycles of Q3W gemcitabine (1000 mg/m²) + carboplatin (AUC 4.5 or 5) / cisplatin (70 mg/m²) followed by maintenance avelumab (800 mg Q2W). Maintenance avelumab treatment will be given up to a maximum of 2 years from the end of chemotherapy in both arms. Following the end of study treatment, patients will attend safety follow up visits at 30 and 90 days post the last dose. Patients will then enter a follow-up phase during which they will be contacted 12 weekly to collect survival and disease status data. The follow-up duration will be until the end of avelumab treatment or for 2 years from completion of chemotherapy, whichever is longer. Patients will have a variety of assessments as part of standard of care treatment, including: medical history, physical examination, ECG, haematology, biochemistry, urinalysis, and tumour assessments. Quality of life will be assessed using patient-reported outcomes from the EORTC-QLQ-C30 questionnaire collected at various timepoints throughout the study. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Avelumab, gemcitabine, carboplatin/cisplatin |
| Primary outcome measure | Quality of life measured using the European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30) from baseline to the completion of 6 cycles of treatment |
| Secondary outcome measures | There are no secondary outcome measures |
| Overall study start date | 12/01/2021 |
| Overall study end date | 31/10/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 320; UK Sample Size: 112 |
| Participant inclusion criteria | 1. Willing and able to provide written informed consent 2. Ability to comply with the protocol, including but not limited to, the repeated completion of the EORTC QLQ-C30 questionnaires 3. Age ≥18 years 4. Histologically confirmed, unresectable locally advanced or metastatic urothelial carcinoma (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Patients with squamous or sarcomatoid differentiation or mixed cell types are eligible but a component of urothelial cancer is required. 5. Measurable disease by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 6. Eligible for gemcitabine/cisplatin or gemcitabine/carboplatin 7. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2 8. Adequate haematologic and organ function 9. Negative serum or urine pregnancy test within 2 weeks of Day 1 Cycle 1 for female patients of childbearing potential only 10. Agreement to use adequate contraceptive measures |
| Participant exclusion criteria | 1. Prior treatment with a PD-(L)-1 inhibitor for any malignancy, including earlier stage UC 2. Prior systemic therapy for locally advanced or metastatic urothelial carcinoma with the following exceptions: a platinum-containing regimen (cisplatin or carboplatin) in the neoadjuvant or adjuvant setting if more than 6 months since the last cycle have occurred. 3. Pregnant and lactating female patients 4. Known history of active CNS metastases 5. Prior allogeneic stem cell or solid organ transplantation 6. Oral or IV steroids for 14 days prior to C1D1 7. Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study 8. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]−2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment 9. Concurrent treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to enrolment 10. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, 11. Malignancies other than urothelial carcinoma of the bladder within 3 years prior to Cycle 1, Day 1 12. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction or cerebral vascular accident/stroke within 6 months prior to enrolment, unstable arrhythmias, or unstable angina 13. Radiotherapy within 2 weeks prior to C1D1 14. Major surgery (defined as requiring general anaesthesia and >24-hour inpatient hospitalization) within 4 weeks prior to randomisation. Patients must have recovered adequately from complications from the intervention prior to starting study treatment. 15. History of idiopathic pulmonary fibrosis (including pneumonitis),drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan (History of radiation pneumonitis in the radiation field (fibrosis) is permitted) 16. Active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. 17. Positive HIV test 18. Active tuberculosis 19. History of autoimmune disease 21. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies 22. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of avelumab 23. Active infection requiring systemic therapy 24. Persisting toxicity related to prior therapy 25. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results 26. Participants with a previous or known history of allergic reaction to cisplatin, gemcitabine, carboplatin or other platinum-containing compounds, or any component of the chemotherapy formulations 27. Patients with bleeding tumours 28. Any other contraindication for gemcitabine/cisplatin or gemcitabine/carboplatin treatment as per the Summary of Product Characteristics (SmPC) |
| Recruitment start date | 12/12/2021 |
| Recruitment end date | 30/06/2025 |
Locations
Countries of recruitment
- United Kingdom
Study participating centre
London
EC1A 7BE
United Kingdom
Sponsor information
University/education
327 Mile End Road
London
E1 4NS
England
United Kingdom
| Phone | +44 (0)20 7882 7275/6574 |
|---|---|
| research.governance@qmul.ac.uk | |
| Website | http://www.qmul.ac.uk/ |
"ROR" |
https://ror.org/026zzn846 |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Merck, Merck Group
- Location
- Germany
Results and Publications
| Intention to publish date | 31/10/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | The full study report will be accessible via EudraCT or another suitable public website within 1 year of the End of the Trial Notification. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to current regulatory requirements not requiring this. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol file | version 4.1 | 25/05/2023 | 15/01/2024 | No | No |
Additional files
Editorial Notes
29/01/2025: The following changes were made:
1. The target number of participants was changed from "Planned Sample Size: 224; UK Sample Size: 112".
2. The recruitment end date was changed from 30/06/2024 to 30/06/2025.
15/01/2024: Protocol uploaded. The recruitment end date was changed from 12/12/2023 to 30/06/2024.
24/04/2023: Cancer Research UK plain English summary link added to plain English summary field.
21/02/2022: Trial's existence confirmed by the NIHR.
