Unresectable locally advanced or metastatic urothelial carcinoma MedDRA version: 20.0 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Avelumab (Bavencio)
Product Name: Avelumab (Bavencio)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Avelumab
CAS Number: 1537032-82-8
Other descriptive na
Sponsors
Queen Mary University of London
Eligibility
Sex/Gender
All
Inclusion criteria
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 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): a. GFR =65 years) yes F.1.3.1 Number of subjects for this age range 179
Exclusion criteria
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 last cycle have occurred. 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: a. CNS metastases have been clinically stable for at least 4 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis b. the subject is on a stable dose of =10 mg/day of prednisone or equivalent for at least 2 weeks prior to C1D1 (if requiring steroid treatment) c. subject does not have leptomeningeal disease 5. Prior allogeneic stem cell or solid organ transplantation 6. Oral or IV steroids for 14 days prior to C1D1. The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids (i.e., for adrenal insufficiency), and mineralocorticoids (e.g., fludrocortisone) is allowed. Patients receiving treatment for CNS metastases at a stable dose of =10 mg/day of prednisone or equivalent for at least 2 weeks prior to screening are eligible. 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, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome) 11. Malignancies other than urothelial carcinoma of the bladder 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: 1. To evaluate the effect of 3 vs 6 cycles platinum-based, front line chemotherapy followed by maintenance avelumab based on additional patient-reported outcomes (PROs) in the study population. 2. To evaluate the effect of 3 vs 6 cycles platinum-based, front line chemotherapy followed by maintenance avelumab based on clinician reported outcomes. 3. To evaluate the safety and tolerability of 3 vs 6 cycles of platinum-based, front line chemotherapy followed by maintenance avelumab therapy. 4. To assess the efficacy of 3 vs 6 cycles platinum based, front line chemotherapy followed by maintenance avelumab in patients with advanced UC.;Primary end point(s): Change in GHS/QoL scale scores from baseline to completion of 6 cycles of treatment. Patients who withdraw from treatment between Cycles 4 and 6 will be included, provided an EORTC QLQ-C30 questionnaire is completed within 14 days after the date of withdrawal.;Timepoint(s) of evaluation of this end point: Patient reported outcomes reported at completion of cycle 6. Patients who withdraw from treatment between Cycles 4 and 6 will be included, provided an EORTC QLQ-C30 questionnaire is completed within 14 days after the date of withdrawal.;Main Objective: To evaluate the effect of 3 vs 6 cycles platinum-based, front line chemotherapy followed by maintenance avelumab based on patient-reported outcomes (PROs) in the study population. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Quality of Life assessment from baseline to the completion of 10 Cycles of treatment using the GHS/QOL scale score, as per the primary endpoint methodology. 2.Quality of Life assessment from the beginning of cycle 5 to the completion of 10 Cycles of treatment using the GHS/QOL scale score, as per the primary endpoint methodology. 3.Change in GHS/QOL scale scores from baseline to the end of assessment (wk54), as per the primary endpoint methodology. 4.The above endpoints will be repeated using the EORTC QLQ-C30 scale score. 5.GHS/QoL scale score time to deterioration (TTD), where deterioration in the GHS/QoL scale score is defined as a decrease by =10 points at any time point after baseline with no subsequent observations with a <10 point decrease from baseline. 6.Change in the GHS/QOL scale score from baseline as per the primary endpoint, but adjusted for baseline imbalances in GHS/QOL scale scores. 7. Performance status as measured by the Karnofsky Scale on completion of 6 cycles of treatment. 8. Incidence, nature and severity of adverse events graded according to NCI-CTCAE v5.0 at the following timepoints: a. Throughout treatment b. On completion of Cycle 6 of treatment c. Between Cycle 4 and the completion of Cycle 10. 9. Treatment discontinuation rate due to AEs. 10. Overall response rate in each randomised treatment arm defined as the proportion of patients who achieved complete response (CR) or partial response (PR) according to RECIST v1.1 recorded from randomisation until week 20. (investigator assessed unconfirmed best response) 11. Progression free survival rate at 20 weeks post randomisation (PFS rate) in each treatment arm defined as the proportion of patients who did not experience disease progression or death from any cause according to RECIST v1.1 recorded from randomisation until week 20. 12. Duration of response defined as the time from first documentation of CR or PR to disease progression (RECIST v1.1) or d | — |
Countries
Spain
Contacts
Public ContactThomas Powles
Queen Mary University of London
Outcome results
None listed