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: 19.0Level: LLTClassification code 10046714Term: Urothelial carcinoma bladderSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-003262-86-IT
- 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 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;
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 independent expedited central 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 (slides not acceptable) from the most recent primary or metastatic tumor biopsy or resection obtained prior to treatment with first line chemotherapy but within one year of randomization, with no intervening systemic anti-cancer therapy. If a suitable tissue sample is not otherwise available, then an FFPE tissue block from a de novo biopsy (core needle or excisional) must have been obtained for research purposes prior to randomization in this study;
5. Provision of an archival FFPE tumor tissue block from primary tumor resection specimen (if not provided per above). If an FFPE tissue block cannot be provided, 15 unstained slides (10 minimum) will be acceptable;
6. 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,
7. Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures;
8. Age above 18 years;
9. Estimated life expectancy of at least 3 months;
10. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1;
11. Adequate bone marrow, renal and liver function;
12. Negative serum pregnancy test at screening (for females of childbearing potential);
13. Male and female patients able to have children 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 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 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 ?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- or hyperthyroid 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).
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 =10 mg/day of prednisone or equivalent;
c.Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
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.Any test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating acute or chronic infection.
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,
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