Clinica study evaluating the efficacy and safety of the combination of cisplatin plus nab-paclitaxel and nivolumab with radiotherapy after maximal tumor resection in non-metastatic muscle invasive bladder cancer.
- Conditions
- Patients with non-metastatic muscle invasive bladder cancer.MedDRA version: 21.1Level: PTClassification code 10066753Term: Bladder transitional cell carcinoma stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-001443-27-IT
- Lead Sponsor
- FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS UNIVERSITA' CATTOLICA DEL SACRO CUORE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 32
1.18 years old or older
2.Histologic diagnosis of predominantly urothelial carcinoma of the bladder. Focal differentiation allowed other than small cell histology.
3.Stage T2-T3 N0M0 (AJCC-TNM version 6) based on trans-urethral resection of bladder tumor (TURBT), CT or MRI imaging, +/- bimanual examination under anaesthesia (EUA).
4.FDG-PET within 6 weeks from the start of treatments, showing no evidence of lymph nodes or metastatic disease.
5.Attempt of complete TURBT within 56 days (8 weeks) prior to the start of chemoradiation. If TURBT was performed > 8 weeks prior but a recent cystoscopy shows no residual disease, then a repeat TURBT is not necessary.
6.Life expectancy greater than 6 months
7.ECOG performance status of 1 or better
8.Another primary cancer is allowed only if treated with curative intent at least 3 years prior to enrolment without evidence of recurrence or if the untreated cancer is clinically indolent (e.g., lower risk prostate cancer).
9.Patients must be considered able to tolerate systemic chemosensitizer combined with pelvic IMRT by the joint agreement of the participating radiation oncologist and medical oncologist.
10.Able and willing to give written informed consent.
11.For women of childbearing potential (WOCBP), study participants must use a contraceptive method that is highly effective (with a failure rate of < 1% per year) for at least 5 months after the last dose of study intervention. Men receiving any study drurg and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of nivolumab.
The investigator or a designated associate is requested to advise the subject how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommend method (or combination of methods) as per standard of care. Acceptable methods are oral contraceptives, hormonal implants, hormonal patches, IDU, Diaphragm with spermicides, cervical cape with spermicide, and condom with spermicide.
12.Adequate bone-marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days of starting the study treatment:
13.Total bilirubin =1·5 × the upper limit of normal (ULN).
14.Alanine aminotransferase and aspartate aminotransferase =2 × ULN (=5 × ULN for patients with liver involvement of their cancer).
15.International normalized ratio (INR) and partial thromboplastin time (PTT) =1·5 × ULN. Subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate if no prior evidence of an underlying abnormality in coagulation parameters exists. Close monitoring with at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care.
16.Platelet count =100 000/mm3, haemoglobin >9 g/dl, absolute neutrophil count >1,500/mm3.
17.Alkaline phosphatase limit =2·5 × ULN (=5 × ULN for patients with liver involvement of their cancer).
18.Creatinine clearance greater than 40 ml/min as evaluated by Cockcroft-Gault formula.
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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12
1.Prior systemic therapy for other urothelial tumours.
2.Prior RT to the pelvis
3.Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug, whichever is longer, prior to enrolment.
4.Malignancies other than urothelial cancer within 3 years prior to Cycle 1, Day 1.
5.Pre-existing medical conditions precluding treatment (e.g., previous history of immune-related adverse reactions, pneumonitis, colitis, etc.)
6.History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
7.History of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
8.Active tuberculosis
9.For women of childbearing potential (WOCBP), study participants must use a contraceptive method that is highly effective (with a failure rate of < 1% per year) for at least 5 months after the last dose of study intervention. Men receiving any study drurg and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of nivolumab.
Acceptable methods are oral contraceptives, hormonal implants, hormonal patches, IDU, Diaphragm with spermicides, cervical cape with spermicide, and condom with spermicide.
10.Received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor [TNFR] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
11.Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial.
12.Active autoimmune disease that has required systemic treatment in past 2 years.
13.Received or will receive a live vaccine within 4 weeks prior to first dose of study drug except for vaccine against SARS-CoViD2. Influenza vaccination should be given during influenza season only (approximately October through May in the Northern Hemisphere and approximately April through September in the Southern Hemisphere). Patients must agree not to receive live, attenuated influenza vaccine (e.g., FluMist®) within 28 days prior to randomization, during treatment or within 5 months following the last dose of nivolumab.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To improve the one-year disease free survival rate. Progression will be evaluated using RECIST 1.1 criteria.;Secondary Objective: To investigate the safety and the activity of the combination of cisplatin plus nab-paclitaxel and nivolumab plus concomitant radiotherapy after maximal tumor resection as a multimodal strategy in patients with non-metastatic muscle invasive bladder cancer.;Primary end point(s): To improve the one-year disease free survival rate. Progression will be evaluated using RECIST 1.1 criteria.;Timepoint(s) of evaluation of this end point: one year
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Rate of patients requiring salvage cystectomy.; Locoregional complete response.; Locoregional disease-free survival.; Median disease-free survival.; Median overall survival; Safety of the combination of nivolumab plus cisplatin and nab-paclitaxel with concomitant RT.; Safety of nivolumab after RT; Quality of life;Timepoint(s) of evaluation of this end point: five years; five years; five years; five years; five years; nine weeks; up to 100 days after last dose of nivolumab; one year