Patients with metastatic urothelial carcinoma who have relapsed after =1 chemotherapy regimen MedDRA version: 20.0 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder System Organ Class: 100000004864
Conditions
Sponsors
FONDAZIONE IRCCS "ISTITUTO NAZIONALE DEI TUMORI"
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Written informed consent. • Age =18 years. • Body weight >30kg • Histologically-confirmed diagnosis of UC or variant histologies (e.g. squamous cell carcinoma, adenocarcinoma, micropapillary tumors, BUT excluding pure small cell carcinoma) of the bladder or the urothelium. • Either bladder, urethral, or upper tract primary tumor will be allowed. • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. • Life expectancy of at = 12 weeks. • Availability of tumor tissue for PD-L1 IHC assay. • Measurable and non-measurable disease will be included (e.g. patients with bone metastases only will be allowed for inclusion). • Failure of 1 or 2 cisplatin-based conventional chemotherapy regimens for metastatic disease (2nd-to-3rd line only). • Neoadjuvant/adjuvant regimens will be counted provided that a relapse occurred with 6 months of the last cycle of chemotherapy. • Adequate function of the organs: a. Absolute neutrophil count (ANC) = 1500/mm3 b. Platelets = 100,000/mm3 c. Hemoglobin = 9 g/dL (= 90 g/L). d. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: • Patients taking regular oral steroids, above the allowed limit of 10mg/day methylprednisolone or analogues, for any reason. Patients must not have had steroids for 28 days prior to study entry. • Malignancies other than bladder carcinoma within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (Gleason score = 3 + 4 and PSA < 10 ng/mL undergoing active surveillance and treatment naive). • Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results. • Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening and prior radiographic assessments. • Patients with treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria (see pg 29) • Pregnant female patients. All female patients of childbearing potential with a positive pregnancy test within 2 weeks prior to the first dose of study treatment will be excluded from the study. • Clinically significant cardiovascular disease, for example, myocardial infarction (within 3months prior to enrolment), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication (beta-blockers and digoxin are allowed) • Uncontrolled hypertension, stroke or other ischemic or thromboembolic event (DVT, PE) within 6 months before first dose of cabozantinib • Severe infections within 4 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia. • Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis. Complete wound healing from major surgery must have occurred 1 month before inclusion and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before inclusion. Subjects with clinically relevant ongoing complications from prior surgery are not eligible • Concomitant anticoagulation with oral anticoagulants or platelet inhibitors • Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption • Patients with a history of aneurysms
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective will be to evaluate whether the combination of durvalumab and cabozantinib will be active and will result in an increased efficacy compared to the available results with the use of both single-agents;Secondary Objective: -the evaluation of the safety and tolerability of durvalumab combined with cabozantinib in a population of chemotherapy pretreated patients with UC - the evaluation of translational correlates of response and outcome;Primary end point(s): The primary endpoint of the study will be overall survival (OS);Timepoint(s) of evaluation of this end point: Duration of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To assess OS in patients with bone metastases only; To assess OS in patients with pure non-urothelial histology; Assessment of RR (investigator-assessed) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. RR (%) = complete (CR) + partial responses (PR).; Assessment of RR according to the immune-related RECIST criteria; FDG-PET response in bone metastases (EORTC criteria); Response duration (including stable diseases ); Progression-Free Survival (investigator-assessed); Correlative biological/immunologic endpoints; incidence, nature and severity of all-cause and treatment-related adverse events (AE), graded with the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0;Timepoint(s) of evaluation of this end point: Duration of the study; Duaration of the study; Duration of the study; Duration of the study; Duration of the study; Duration of the study; Duration of the study; Duration of the study; Duration of the study | — |
Countries
Italy
Contacts
Public ContactClinical Trial Center
Fondazione IRCCS Istituto Nazionale dei Tumori
Outcome results
None listed