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-DK
- 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 received
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 investigator review of pre-chemotherapy and postchemotherapy
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 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 submitted;
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 firstline
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 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 Grade <=2 adverse eventsnot constituting a safety risk based on
the investigator's judgment 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 lowgrade
(Gleason 6 or below) prostate cancer on surveillance without any
plans for treatment intervention (eg, surgery, radiation, or castration),
or prostate cancer that has been adequately treated with prostatectomy
or radiotherapy and currently 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. Clinically significant (ie, active) cardiovascular disease: cerebral
vascular accident/stroke (< 6 months prior to enrollment), myocardial
infarction (< 6 months prior to enrollment), unstable angina, congestive
heart failure, or serious cardiac arrhythmia 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;
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) infection 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 vaccines);
19. Patients who are investigational site staff members directly involved
in the conduct
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