a study of toca 511 & toca fc in patients with recurrent high grade non-muscle invasive bladder cancer (toca 8)

Conditions: Bladder Cancer

Summary: this is a phase 1, multicenter, open-label study of intravesical toca 511 followed by oral toca fc in patients with high grade (hg) non-muscle invasive bladder cancer (nmibc), with cohort expansion at the recommended phase 2 dose. patients with recurrent hg nmibc who are undergoing planned transurethral resection of bladder tumor (turbt) will be enrolled into the study, subject to meeting all entry criteria.


Eligibility criteria:
inclusion criteria: * provide written informed consent to participate * at least 18 years of age * recurrent hg nmibc, with hg tumor on previous histopathology * undergoing planned turbt and biopsy of cis suspicious areas * no imaging findings consistent with t2 or greater disease, hydronephrosis, extravesical disease, nodal involvement, metastases, or other malignancies. * able and willing to wait at least 2 weeks following intravesical administration of toca 511 to undergo turbt * if patient is a candidate for standard of care (soc) intravesical therapy, able and willing to wait at least 2 weeks post-turbt for initiation of such treatment * patient is able to be catheterized and is anticipated to be able to retain toca 511 for approximately 2 hours * estimated life expectancy of at least 12 months * eastern cooperative oncology group (ecog) performance status score of 0 or 1 * patient has adequate organ function, as indicated by the following laboratory values * complete blood count: hemoglobin ≥ 10 g/dl, platelet count ≥ 100,000/mm\^3, absolute neutrophil count ≥ 1,500/ mm\^3, absolute lymphocyte count ≥ 500/ mm\^3 * liver: total bilirubin ≤ 1.5 × the upper limit of normal (uln; unless known gilbert's syndrome); alanine aminotransferase ≤ 2.5 × uln * kidney: estimated glomerular filtration rate (gfr: cockcroft-gault) ≥ 50 ml/min * women of childbearing potential (defined as not postmenopausal \[ie, ≥ 12 months of non-therapy-induced amenorrhea\] or not surgically sterile) must have a negative serum pregnancy test within 7 days prior to administration of toca 511, and be willing to use an effective means of contraception in addition to barrier methods (condoms) for the duration of the study. * patient and partner are willing to use condoms for 12 months after receiving toca 511 and/or 30 days after the last dose of toca fc, and/or until there is no evidence of the virus in his/her blood or urine, whichever is longer. exclusion criteria: * history of urothelial cancer in the upper tract or urethra; muscle invasive bladder cancer; or metastatic bladder cancer * history of bladder tumors other than urothelial carcinoma (ie, neuroendocrine, adenocarcinoma, or squamous cell carcinoma) * treatment with intravesical agents within 28 days prior to toca 511 administration * turbt within 12 weeks prior to planned toca 511 administration * history of pelvic radiation * bladder tumor located within a bladder diverticulum * genitourinary procedures (eg, prostate surgery; treatment of ureteral stones or moderate to extensive urethral stricture disease) prior to, during, or planned within the 4 weeks following turbt, other than procedures for treatment of bladder tumors * severe lower urinary tract dysfunction clinically manifest as poor capacity, disabling incontinence, chronic catheter use, or chronic infections or stones * presence of suprapubic catheter * history of other malignancy, unless the patient has been disease-free for at least 5 years. adequately treated basal cell carcinoma or squamous cell skin cancer is acceptable regardless of time, as well as cervical carcinoma in situ or localized prostate carcinoma, after curative treatment. (note: men with very low or low risk prostate cancer on active surveillance are acceptable candidates for this study.) * active infection requiring antibiotic, antifungal, or antiviral therapy within 2 weeks prior to administration of toca 511 * investigational treatment within 2 weeks or immunotherapy or antibody therapy within 28 days prior to toca 511 administration, and/or has not recovered from toxicities associated with such treatment * chronic treatment with autoimmune medications * human immunodeficiency virus (hiv) seropositive * pregnant or breast feeding * bleeding diathesis, or required to take anticoagulants or antiplatelet agents, including nonsteroidal anti-inflammatory drugs, that cannot be stopped for surgery * severe pulmonary, cardiac, or other systemic disease, specifically: * new york heart association \> class ii congestive heart failure that is not controlled on standard therapy within 6 months prior to toca 511 administration * uncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes), clinically significant pulmonary disease (such as ≥ grade 2 dyspnea) * any other serious medical, social, or psychological condition that, based on investigator assessment, may affect the patient's compliance or place the patient at an increased risk of potential treatment complications * history of allergy or intolerance to flucytosine * presence of a condition that would prevent the patient from being able to swallow toca fc tablets

Keywords: non-muscle invasive bladder cancer bladder cancer high grade non-muscle invasive bladder cancer hg nmibc nmibc high grade nmibc