Informations générales (source: ClinicalTrials.gov)
A Randomised Phase II Study Comparing 3 vs 6 Cycles of Platinum-based Chemotherapy Prior to Maintenance Avelumab in Advanced Urothelial Cancer
Interventional
Phase 2
Queen Mary University of London (Voir sur ClinicalTrials)
décembre 2021
décembre 2027
07 mai 2026
This is an adaptive, open-label, randomised phase II trial that aims to evaluate the
impact of 3 vs 6 cycles of first-line platinum-based chemotherapy followed by maintenance
avelumab in the quality of life of patients with locally advanced or metastatic
urothelial cancer. Initially, 224 eligible and evaluable patients (112 in each arm) will
receive 3 cycles vs 6 cycles of 3-weekly gemcitabine plus cisplatin/carboplatin, followed
by 2-weekly maintenance avelumab until disease progression or intolerable toxicities.
Avelumab treatment will be given up to a maximum of 2 years from the end of chemotherapy.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| HOPITAL FOCH | Christine ABRAHAM | 11/05/2026 07:26:37 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Unicancer - Paris - France | Yohann Loriot | Contact (sur clinicalTrials) | |||
Critères
Tous
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 RECIST v1.1.
6. Eligible for gemcitabine/ cisplatin or gemcitabine/carboplatin. The following
criteria are established for the use of carboplatin (patients not fulfilling the
following carboplatin criteria should be considered for gemcitabine/ cisplatin):
1. GFR <60 mL/min but ≥30 mL/min (measured by the Cockcroft-Gault formula or by
local accepted standards). Subjects with a GFR ≥50 mL/min and no other
cisplatin ineligibility criteria may be considered cisplatin-eligible based on
the investigator's clinical judgement.
2. ECOG or WHO performance status of 2.
3. NCI CTCAE Grade ≥2 audiometric hearing loss.
4. NYHA Class III heart failure.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2.
8. Adequate haematologic and organ function as defined below:
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
Exclusion Criteria:
- 1. Prior treatment with a PD-(L)-1 inhibitor for any advanced malignancy. Treatment
with PD-(L)-1 inhibitors in the neoadjuvant or adjuvant setting for UC are
permitted.
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 last
cycle have occurred. Patients who received adjuvant or neoadjuvant immune therapy
for muscle invasive or non-muscle invasive disease are eligible.
3. Pregnant and lactating female patients. 4. Known history of active CNS
metastases. Patients with treated CNS metastases are permitted on the study if all
of the following are true: 5. Prior allogeneic stem cell or solid organ
transplantation. 6. 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.
7. 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 (see section 11.26).
8. Concurrent treatment with any other investigational agent or participation in
another clinical trial with therapeutic intent within 4 weeks prior to enrolment.
9. Evidence of significant uncontrolled concomitant disease that could affect
compliance with the protocol or interpretation of results, including significant
liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior
vena cava syndrome).
10. Malignancies other than urothelial carcinoma within 3 years prior to Cycle 1,
Day 1, with the exception of those with a negligible risk of metastasis or death and
treated with expected curative outcome (such as adequately treated carcinoma in situ
of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ
treated surgically with curative intent) or localized prostate cancer treated with
curative intent and absence of prostate-specific antigen (PSA) relapse or incidental
prostate cancer (Gleason score ≤ 3 + 4 and PSA < 10 ng/mL undergoing active
surveillance and treatment naive). .
11. 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.
12. Radiotherapy within 2 weeks prior to C1D1. Patients must have recovered
adequately from toxicities resulting from the intervention prior to starting study
treatment.
13. 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.
14. 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).
15. 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.
16. Positive HIV test. 17. Active tuberculosis. 18. Active autoimmune disease
including but not limited to myasthenia gravis, myositis, autoimmune hepatitis,
systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease,
vascular thrombosis associated with antiphospholipid syndrome, Wegener's
granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis,
vasculitis, or glomerulonephritis.
19. History of autoimmune-related hypothyroidism, unless on a stable dose of thyroid
replacement hormone.
20. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies.
21. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese
hamster ovary cells or any component of avelumab.
22. Active infection requiring systemic therapy. 23. Persisting toxicity related to
prior therapy (NCI CTCAE Grade > 1); however, alopecia, sensory neuropathy Grade ≤
2, or other Grade ≤ 2 not constituting a safety risk based on investigator's
judgment are acceptable.
24. Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results
25. Participants with previous or known history of allergic reaction to cisplatin,
gemcitabine, carboplatin or other platinum containing compounds, or any component of
the chemotherapy formulations.
26. Patients with bleeding tumours 27. Any other contraindication for gemcitabine/
cisplatin or gemcitabine/carboplatin treatment as per SmPC.