A study in patients with bladder cancer using a combination of nivolumab and NKTR-214
- Conditions
- ocally advanced or metastatic urothelial bladder cancerTherapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864
- Registration Number
- EUCTR2018-003636-79-NL
- Lead Sponsor
- ektar Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 190
Each patient will be entered into this study only if he/she meets all of the following criteria:
• Male or female patients, age 18 years or older at the time of signing the informed consent form (ICF).
• Patients must have histologically or cytologically documented inoperable, locally advanced (T4b, any N; or any T, N2-3) or metastatic (M1, Stage IV) urothelial cell carcinoma (also termed transitional cell carcinoma) including renal pelvis, ureters, urinary bladder and urethra.
• Histologically or cytologically confirmed locally advanced and unresectable or metastatic urothelial cancer, including mixed urothelial cell and non-urothelial cell histologies. If the histology is mixed with non-urothelial carcinoma (e.g., squamous cell carcinoma), the urothelial cell component must be dominant (> 50% of the total histology).
• Tumor tissue is required to be analyzed by central laboratory to document PD-L1 status
TIssue can be provided in 1 or 2 ways:
-a new biopsy taken during screening
-Archival tissue from either a FFPE tissue block or unstained tumor tissue sections. Archival tissue must be obtained within 12 months prior to enrollment and with no intervening treatment
• A tracking number confirming shipment of the sample to the central laboratory must be supplied prior to Cycle 1 Day 1.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 2.
• Patients must have measurable disease per RECIST 1.1 criteria, and have adequate organ function.
• Patients must be able and willing to comply with the study visit schedule and study procedures.
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 65
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 125
exclusion criteria:
1. Female patients who are pregnant or lactating, who plan to get pregnant, or who have a positive serum or urine pregnancy test.
2. Active brain metastases or leptomeningeal metastases. Patients with brain metastases are eligible if these have been treated and there is no radiographic evidence of progression for at least 4 weeks after treatment is complete (confirmed by the head imaging obtained within 28 days prior to Cycle 1 day 1). There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to Cycle 1 day 1. Stable dose of anticonvulsants is allowed. Patients with CNS metastases treated by neurosurgeical resection or brain biopsy performed within 28 days prior to Cycle 1 Day 1 are not eligible.
3. Prior active malignancy within the previous 3 years except for locally curable cancers with negligible risk of metastases or death that have been treated with expected curative outcome, such as basal or squamous cell skin cancer, carcinoma in situ of the prostate, cervix or breast. An incidental finding of prostate cancer (identified upon resection of the prostate) is acceptable, provided that one of the following criteria is met: T2N0M0 or Gleason score = 3+4, or prostate - specific antigen (PSA) below upper limit of normal by local laboratory and not requiring active treatment.
4. Patients who have an active, known or suspected autoimmune disease. Patients requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents.
5. Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of Cycle 1 Day 1.
6. Patients must not have received prior IL-2 therapy.
7. Patients who have received any live / attenuated vaccine within 30 days before Cycle 1 Day 1.
8. Prior treatment with an anti PD-1, anti PD-L2, or anti CTLA-4 antibody, agents that target IL-2 pathway, or any other antibody or drug specifically targeting T- cell costimulation or immune checkpoint pathways.
9. History of allergy to study drug components.
10. History of severe hypersensitivity reaction to any monoclonal antibody.
11. History of organ hematopoetic, or tissue transplant that requires the systemic use of immune suppressive agents.
12. Active infection requiring systemic therapy within 14 days prior to Cycle 1 Day 1.
13. Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus.
14. Known history of positive test for human immunodeficiency virus or known acquired immunodeficiency syndrome.
15. Known cardiovascular history including unstable or deteriorating cardiac disease within the previous 12 months prior to screening including but not limited to the following:
a) Unstable angina or myocardial infarction
b) Transient ischemic attack (TIA)/Cerebrovascular accident (CVA)
c) Congestive heart failure (New York Heart Association [NYHA] Class III or IV)
d) Uncontrolled clinically significant arrhythmias
16)History of pulmonary embolism (PE), deep vein thrombosis (DVT), or prior clinically significant venous or non-CVA/TIA arterial thromboembolic event within 3 months prior to enrollment.
16. Patients with hypertension must be on a stable antihypertensive regimen for the 14 days
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