Localized muscle invasive bladder cancer MedDRA version: 20.0 Level: LLT Classification code 10022878 Term: Invasive bladder cancer stage II System Organ Class: 100000004864
Conditions
Sponsors
Spanish Oncology Genitourinary Group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients diagnosed with urothelial carcinoma of the bladder, in clinical stages T2-4a N0 M0, who are not candidates for radical cystectomy by medical reasons, refusal or patient’s choice. 1. Patients must have signed the informed consent prior to undergoing any study procedure. 2. Patients must be 18 years of age or older. 3. Patients must have ECOG performance status 0 or 1. 4. A paraffin-embedded tumor sample must be available for the associate molecular study. 5. Body weight >30 Kg. 6. Adequate normal organ and marrow function as defined in section 4.1 of this protocol. 7. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients, according to what is detailed in section 4.1 of this protocol. 8. Patient is willing and able to comply with the protocol for the duration of the study. 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 32 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 32
Exclusion criteria
Exclusion criteria: 1. Involvement in the planning and/or conduct of the study (applies to both Sponsor staff and/or staff at the study site) 2. Participation in another clinical study with an investigational product during the last 30 days. 3. 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. 4. Previous treatment with radiotherapy to the bladder, systemic chemotherapy or immune checkpoint inhibitors. Prior intravesical Bacillus Calmette-Guérin (BCG) treatment for non- muscle invasive bladder cancer is allowed, 28 days prior to study. 5. Presence of regional lymph node or metastatic extension of the disease. 6. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) =470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart) >. 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. Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician. 8. Any concurrent chemotherapy, investigational product (IP) other than studied in this protocol, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non–cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 9. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. 10. History of allogenic organ transplantation. 11. Active or prior documented autoimmune or inflammatory disorders, as it is detailed in section 4.2 of this protocol. 12. Uncontrolled intercurrent illness, please see section 4 of this protocol. 13. History of another primary malignancy as detailed in section 4 of this protocol. 14. History of active primary immunodeficiency 15. Active infection (see section 4 of this protocol) 16. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. Exceptions are listed in section 4 of this protocol. 17. Receipt of live attenuated vaccine within 30 days prior to the first dose of IMP 18. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control according what is detailed in this protocol (section 4). 19. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. 20. Prior randomisation or treatment in a previous durvalumab and/or tremelimumab clinical study. 21. Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements. 22. Known allergy or hypersensi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of durvalumab plus tremelimumab with concurrent radiotherapy in terms of pathological response rate in patients with localized muscle invasive bladder cancer treated with bladder preservation intent.;Secondary Objective: - To determine the rate of patients with bladder preserved, the rate of immediate and late salvage cystectomies and the survival with bladder preserved free of tumor, defined as the time from the start of immunotherapy to either the date of cystectomy or the date of recurrence of muscle-invasive bladder carcinoma or metastasis. - To determine the disease-free survival, defined as the time from the start of therapy to the date of recurrence of muscle invasive bladder carcinoma or metastases, and overall survival, defined as the time from the start of immunotherapy to the date of death due to any cause. - To assess the safety profile and tolerability of the combination of durvalumab plus tremelimumab with concurrent radiotherapy. - To evaluate the long-term functionalism and late sequelae of the treatment in the preserved bladders.;Primary end point(s): Efficacy based on the pathological response evaluated by biopsy (performed via cytoscopy) at the end of treatment.;Timepoint(s) of evaluation of this end point: Patients will be followed up every 3 months the first year, every 4 months the second year and every 6 months thereafter with abdomen and pelvis CT scan, Rx thorax, urine cytology. Additional cystoscopy and bladder biopsy will be performed anytime in case of detection abnormalities in the cytology or imaging studies. The study will be closed 2 years after the last patient inclusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Rate of patients with bladder preserved, rate of immediate and late salvage cystectomies. - Survival with bladder preserved free of tumor, defined as the time from the start of immunotherapy to either the date of cystectomy or the date of recurrence of muscle- invasive bladder carcinoma or metastasis. - Disease-free survival, defined as the time from the start of therapy to the date of recurrence of muscle invasive bladder carcinoma or metastases, and overall survival, defined as the time from the start of immunotherapy to the date of death due to any cause. - Safety profile and tolerability of the combined-modality treatment - Long-term functionalism and late sequelae of the treatment in the preserved bladders.;Timepoint(s) of evaluation of this end point: 2 years for secondary endpoints except for safety profile and tolerability of the combined-modality treatment (12 weeks of first 5 patients) | — |
Countries
Spain
Contacts
Public ContactFederico Nepote
MFAR Clinical Research
Outcome results
None listed