A Study of Avelumab in Patients with Bladder Cancer that did Not Worsen Following Completion of First-Line Chemotherapy
- Conditions
- ocally advanced or metastatic urothelial cancerMedDRA version: 20.0Level: LLTClassification code 10046714Term: Urothelial carcinoma bladderSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-003262-86-NL
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 668
1. Histological diagnosis of confirmed, unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium. patients with documented Stage IV disease (per American Joint Committee on cancer/International Union for Cancer Control Tumor Node Metastasis (TNM) system 7th edition) at the start of first-line chemotherapy and 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. The last dose of first-line chemotherapy must have been recieved no less than 4 weeks, and no more than 10 weeks, prior to randomization;
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. Eligibility based on this criterion will be determined by an investigator review of pre-chemotherapy and post-chemotherapy radiological assessments (CT/MRI scans);
4. Provision of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block (subsection thereof) from the most recent primary or metastatic tumor biopsy or resection obtained prior to treatment with first line chemotherapy but within 24 months prior to randomization, with no intervening systemic anti-cancer therapy. If a suitable tissue sample is not otherwise available. If a FFPE tissue block cannot be provided 15 freshly cut unstained slides (10 minimum) will be acceptable. Tumor tissue from cytologic sampling (eg, fine needle aspiration, including FFPE cell pellet material) or bone metastases are not acceptable and should not be sumbitted;
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 above 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, renal and liver function;
11. Negative serum pregnancy test at screening (for females of childbearing potential);
12. Female patients able to have children must agree to use a highly effective method of contraception throughout the study and for at least 30 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 187
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 481
1. Patients whose disease progressed by RECIST v1.1 on or after first-line chemotherapy for urothelial cancer;
2. Prior adjuvant or neoadjuvant (systemic) therapy within 12 months of randomization;
3. Prior immunotherapy with IL-2, IFN-a, or an anti-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 within 4 weeks or major radiation therapy within 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, alopecia, sensory neuropathy Grade <= 2 is acceptable, or other Grad <= 2 adverse events not constituting a safety risk based on the investigator's judgement are 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 or below) prostate cancer on surveillance without any plans for treatment intervention (eg, surgery, radiation, or castration), or prostate cancer that had been adequatley treated with prostatectomy or radiotherapy and currentley with no evidence of disease or symptoms;
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- or hyperthyroid disease not requiring immunosuppressive treatment are eligible;
10. Clinicaly significant (ie, active) cardiovascualr disease; cerebral vascular accident/stroke (<6 monts prior to enrolment), myocardial infarction (<6months prior to enrolment), unstable angina, congestive heart failure, or serious cardiac arrytmia requiring medication;
11. Active infection requiring systemic therapy;
12. Known severe hypersensitivity reactions to monoclonal antibodies (Grade >= 3), any history of anaphylaxis, or uncontrolled asthma;
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;
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. Positive test for human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS)
17. Hepatitis B virus (HBV) or hepatitis C virus (HCV) at screening
18. Vaccination within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivate vaccines (for example, inactivated influenza
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method