assessment of safety, tolerability, radiation dosimetry, and imaging properties of 89zr-labeled girentuximab (89zr-girentuximab) in patients with non-muscle-invasive bladder cancer (nmibc)

Conditions: Bladder Cancer

Summary: the purpose of this study is to evaluate the use of 89zr-labeled girentuximab (89zr-tlx250) as a novel, carbonic anhydrase ix (caix) targeted pet/ct radiopharmaceutical for the imaging of non-muscle-invasive bladder cancer (nmibc) patients.

there is a real need for treatment of nmibc. currently, treatment options include bacillus calmette-guerin (bcg) intravesical immunotherapy and mitomycin c chemotherapy. these therapies are efficient for some time but relapses repeat them at more and more close intervals and finally patients are refractory to them and require a radical cystectomy. caix is expressed in 70% to 90% of bladder cancers but not in normal urothelial tissue. caix is expressed on the membrane of non-muscle-invasive bladder cancer cells. girentuximab, an anti-caix antibody could be a promising target in nmibc. pet/ct with girentuximab labelled with 89zirconium will be used for diagnosis purpose. 89zr-girentuximab will be administered by intravesical instillation. in this study, patients with non-muscle-invasive bladder cancer (nmibc) will be enrolled in this study after confirmation of their eligibility. a single intravesical administration of 89zr-girentuximab will be performed at day 0. multiple pet/ct imaging sessions will be performed on day 0, day 1 and day 2 in order to evaluate the bladder and the whole body 89zr girentuximab uptake.

Eligibility criteria:
inclusion criteria: * written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations. * willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. * female or male, age ≥ 18 years at time of study entry. * performance status: 0 or 1. * clinical evidence of nmibc based on cystoscopy and proven histologically of papillary tumors. * histologically-confirmed pta grade 3 or pt1 grade 3 bladder cancer patients relapsing without muscle invasion. * negative sterile urine cytobacteriological testing at baseline (t0). * consent to use a contraception method for at least 30 days after administration of 89zr-girentuximab. * patient has valid health insurance. exclusion criteria: * patient with urinary incontinence. * known hypersensitivity to girentuximab. * exposure to any experimental diagnostic or therapeutic drug within 30 days prior the date of planned administration of 89zr-girentuximab * exposure to any radiopharmaceutical within 30 days (corresponding to 10 half-lives of zr-89) prior to the administration of 89zr-girentuximab * patients suffering from a bladder cancer at stage pt2, pt3 or pt4 * serious non-malignant disease that may interfere with the objectives of the study or with the safety or compliance of the patient; as judged by the investigator * concomitant cancer in the past 5 years except cutaneous cancers (except melanoma) and in situ carcinoma * prior chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy), immunotherapy within 21 days of 89zr-girentuximab administration * patients with known human immunodeficiency viruses (hiv), hepatitis b virus (hbv) and hepatitis c virus (hcv) infections, * pregnant or likely to be pregnant or nursing patient. * mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study * persons deprived of their liberty, under a measure of safeguard of justice, under guardianship or placed under the authority of a guardian.

Keywords: non-muscle-invasive bladder cancer (nmibc) patients 89zr-girentuximab ((89zirconium-girentuximab) pet/ct safety assessment pilot study feasibility study 89zr-tlx250 (89zirconium-tlx250) pet/ct positron emission tomography/computerized tomography (pet/ct) scan carbonic anhydrase ix (caix)