Patients with advanced/metastatic urothelial cancer whose disease has not progressed after at least 4 cycles of first line platinum-based chemotherapy.
Conditions
Interventions
Trade Name: avelumab
Pharmaceutical Form: Solution for infusion
Sponsors
Erasmus MC Cancer Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis: a. Histologically confirmed, unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium. b. Documented Stage IV disease (T4b, N0, M0; any T, N1–N3, M0; any T, any N, M1) at the start of first-line chemotherapy. c. Measurable disease prior to the start of first-line chemotherapy by RECIST v1.1. 2. Prior first-line chemotherapy must have consisted of at least 4 cycles and no more than 6 cycles of gemcitabine + cisplatin and/or gemcitabine + carboplatin. No other chemotherapy regimens are allowed in this study. 3. Patients without progressive disease as per RECIST v1.1 guidelines (ie, with an ongoing CR, PR, or SD) following completion of 4 to 6 cycles of first-line chemotherapy. 4. Plasma samples: Provision of a baseline plasma sample is mandatory 5. Evidence of a signed and dated informed consent document indicating that the patient (or a legally acceptable representative, as allowed by local guideline/practice) has been informed of all pertinent aspects of the study. 6. Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. 7. Age; Minimum of 18 years 8. Estimated life expectancy of at least 3 months. 9. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. 10. Adequate bone marrow function, including: a. Absolute neutrophil count (ANC) 1,500/mm3 or 1.5 x 109/L; b. Platelets 100 x 109/L; c. Hemoglobin 5.6 mmol/L (may have been transfused). 11. Adequate renal function, defined as estimated creatinine clearance 50 mL/min as calculated using the Cockcroft-Gault equation 12. Adequate liver function, including: a. Total serum bilirubin 1.5 x upper limit of normal (ULN); b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)2.5 x ULN. 13. Serum pregnancy test (for females of childbearing potential) negative at screening. 14. Male patients able to father children and female patients of childbearing potential and at risk for pregnancy must agree to use 2 highly effective methods of contraception throughout the study and for at least 60 days after the last dose of assigned treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 51 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: Patients with any of the following characteristics/conditions will not be included in the study: 1. Patients whose disease progressed by RECIST v1.1 on or after first-line chemotherapy for urothelial cancer. 2. Prior adjuvant or neoadjuvant therapy within 12 months of randomization. 3. Prior immunotherapy with IL-2, IFN-?.-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways. 4. Major surgery 4 weeks or major radiation therapy 2 weeks prior to randomization. Prior palliative radiotherapy (10 fractions) to metastatic lesion(s) is permitted, provided it has been completed at least 48 hours prior to patient randomization. 5. Patients with known symptomatic central nervous system (CNS) metastases requiring steroids. Patients with previously diagnosed CNS metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to randomization, have discontinued corticosteroid treatment for these metastases for at least 4 weeks, and are neurologically stable. 6. Persisting toxicity related to prior therapy NCI CTCAE v4.0 Grade >1; however, sensory neuropathy Grade 2 is acceptable. 7. Diagnosis of any other malignancy within 5 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason 6) prostate cancer on surveillance without any plans for treatment intervention (eg, surgery, radiation, or castration). 8. Participation in other studies involving investigational drug(s) within 4 weeks prior to randomization. Observational studies are permitted. 9. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo orhyperthyroid disease not requiring immunosuppressive treatment are eligible. 10. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis, or symptomatic pulmonary embolism. 11. Active infection requiring systemic therapy. 12. Known severe hypersensitivity reactions to monoclonal antibodies (Grade 3), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of asthma symptom control per the Global Initiative for Asthma 2015). 62 13. Known prior or suspected hypersensitivity to study drugs or any component in their formulations. 14. Current or prior use of immunosuppressive medication within 7 days prior to randomization, EXCEPT the following: a. Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection); b. Systemic corticosteroids at physiologic doses equivalent; c. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication). 15. Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive therapy, or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. 16. Any test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating acute or chronic infection. 17. Vaccination within 4 weeks of the first dose of study treatment and while on trial is prohibited except for admin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the benefit of maintenance treatment with a maximum of six months avelumab plus best supportive care (BSC) in prolonging overall survival (OS) at 18 months in patients with unresectable locally advanced or metastatic UC whose disease did not progress on or following completion of first-line platinum-containing chemotherapy in all randomized patients.;Secondary Objective: OS in PD-L1 positive and PD-L1 negative tumours, and in re-treated patients. PFS in PD-L1 positive and PD-L1 negative tumours, and in re-treated patients. ORR per RECIST 1.1 in retreated patients. Duration of response. Disease control (defined as complete response, partial response, non–complete response or non–progressive disease, or stable disease at 24 weeks after initiation of avelumab and prior to disease progression or death due to any cause., according to RECIST 1.1).;Primary end point(s): 18 months overall survival (OS);Timepoint(s) of evaluation of this end point: 18 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): OS in PD-L1 positive and PD-L1 negative tumours, and in re-treated patients. PFS in PD-L1 positive and PD-L1 negative tumours, and in re-treated patients. ORR per RECIST 1.1 in retreated patients. Duration of response. Disease control (defined as complete response, partial response, non–complete response or non–progressive disease, or stable disease at 24 weeks after initiation of avelumab and prior to disease progression or death due to any cause., according to RECIST 1.1).;Timepoint(s) of evaluation of this end point: Amongst others at 24 weeks | — |
Countries
Netherlands
Contacts
Public ContactD. Robbrecht
Erasmus MC Cancer Institute
Outcome results
None listed