Patients aged 18 years or older with histologically or cytologically documented locally advanced (on the TNM staging system, T4b and any N
Conditions
Sponsors
CONSORZIO ONCOTECH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations; 2. Patients are eligible for enrolment if they have histologically or cytologically documented locally advanced (on the TNM staging system, T4b and any N; or any T and N2–3) or metastatic (M1, stage IV) urothelial carcinoma (including of the renal pelvis, ureter, urinary bladder, or urethra) who are eligibile to receive first-line systemic treatment and are judged to be ineligible for cisplatin treatment because of ECOG performance status= 2; 3. Age > 18 years at time of study entry; 4. All patients must have measurable disease defined by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1); 5. Eastern Cooperative Oncology Group (ECOG) performance status of 2; 6. Life expectancy of > 12 weeks; 7. Body weight >30kg; 8. Adequate normal organ and marrow function 9. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered postmenopausal if they have been amenorrheic for 12 months without an alternative medical cause 10. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 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 24 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: 1. Participation in another clinical study with an investigational product during the last 28 days, 2. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study, 3. Any prior systemic anticancer therapy received against urothelial carcinoma, with the exception of neoadjuvant or adjuvant chemotherapy if the last dose was administered > 12 months before study inclusion, 4. Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab, 5. History of another primary malignancy 6. Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s Correction, 7. Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria, 8. Any concurrent chemotherapy, Investigational Product (IP), biologic, or hormonal therapy for cancer treatment. 9. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug, 10. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Local surgery of isolated lesions for palliative intent is acceptable, 11. History of allogenic organ transplantation, 12. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). 13. Uncontrolled intercurrent illness, 14. History of leptomeningeal carcinomatosis, 15. Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry, 16. History of active primary immunodeficiency, 17. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 18. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. 19. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP, 20. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab, 21. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients, 22. Patients with ECOG performance status of 0-1 -3-4 must be excluded. 23. Judgment by the investigator that the patient is unsuitab
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to assess the overall response rate as evaluated according to RECIST 1.1 criteria;Secondary Objective: Secondary objectives are to assess the following: a) Overall response rate according to iRECIST criteria b) Progression free survival according to RECIST 1.1 criteria c) Progression free survival according to iRECIST criteria d) Safety e) Overall survival f) Duration of radiological response g) Overall survival rate % after 6 months h) Quality of life as determined according to the FACT-Bladder questionnaire v4;Primary end point(s): Radiological response rate according to RECIST 1.1 criteria among all evaluable patients.;Timepoint(s) of evaluation of this end point: Patients will have scans done every 8 weeks for the first 24 weeks, and then every 12 weeks thereafter (relative to the date of inclusion) until confirmed PD. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy end points include the following: a) Radiological response rate according to iRECIST criteria among all evaluable patients, b) Progression free survival, defined as time since radiological baseline evaluation to time of PD as defined in protocol section 9.1.2 , c) Overall survival, defined as time since inclusion in the study to time of death d) Duration of radiological response, as defined as time since achievement of a radiological response according to the RECIST 1.1 criteria to PD, e) Overall survival rate % after 6 months, defined as the % of patients alive after 6 months among all patients included, f) Quality of life as determined according to the FACT-Bladder questionnaire (FACT-Bl v 4).;Timepoint(s) of evaluation of this end point: I pazienti eseguiranno scansioni ogni 8 settimane per le prime 24 settimane e successivamente ogni 12 settimane (relativamente alla data dell'inclusione) fino alla conferma della PD. OS - Patient level: Assessments midway through Cycles 1, 2 and 3: days 14 of C1, 2 and 3 during treatment period and every 12w post IP discontinuation until the end of the study (24 months) or ICF withdrawn. | — |
Countries
Italy
Contacts
Public ContactProject Manager
Clinical Research Technology Srl
Outcome results
None listed