A Study of Toca 511 & Toca FC in Patients With Recurrent High Grade Non-Muscle Invasive Bladder Cancer (Toca 8)

NCT04089163 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: Tg 511-19-01
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Bladder Cancer

Keywords

non-muscle invasive bladder cancer; bladder cancer; high grade non-muscle invasive bladder cancer; HG NMIBC; NMIBC; high grade NMIBC

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicities

  * Any treatment-related Grade 3 or higher non-hematologic toxicity, excluding nausea, vomiting, or diarrhea that are controllable with appropriate medical measures (eg, antiemetics, antimotility drugs) * Any treatment-related Grade 4 or higher hematologic toxicity

  5 weeks

Secondary Outcomes (2)

• Differences in viral transduction of Toca 511 at each dose level, based on quantitation of viral RNA and DNA in tumor

  3 weeks (+/- 1 week)

• Clearance of viral RNA in plasma and urine, based on real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), and of viral DNA in whole blood and urine, based on quantitative PCR (qPCR)

  1 week for plasma, 4 weeks for urine

Other Outcomes (5)

• Changes from baseline in immune activity in tumor, peripheral blood, and urine

  21 weeks

• Complete response rate at 6 and 12 months in patients with carcinoma in situ (CIS)

  Proportion of patients with CIS with complete response at 6 and 12 months

• High-grade recurrence-free survival

  Event free survival overall and at 6 and 12 months

Study Arms (1)

Sequential Dose Cohorts

EXPERIMENTAL

Doses of Toca 511 will be evaluated in sequential cohorts. Toca 511 will be administered as a single intravesical instillation. Following Toca 511 administration, Toca FC will be administered orally at a dose of 220 mg/kg/day for 7 days every 6 weeks.

Biological: Toca 511; Drug: Toca FC (extended-release formulation of flucytosine)

Interventions

Toca 511 BIOLOGICAL

Toca 511 consists of a purified retroviral replicating vector encoding a modified yeast cytosine deaminase (CD) gene. The CD gene converts the antifungal drug, flucytosine (5-fluorocytosine; 5-FC) to the anticancer drug 5-fluorouracil (5-FU) in cancer cells that have been infected by the Toca 511 vector.

Also known as: vocimagene amiretrorepvec, retroviral replicating vector (RRV)

Sequential Dose Cohorts

Toca FC (extended-release formulation of flucytosine) DRUG

Toca FC is an extended-release formulation of flucytosine and is supplied as 500 mg tablets

Also known as: flucytosine, 5-fluorocytosine (5-FC)

Sequential Dose Cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Tocagen Inc.: lead

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Interventions

vocimagene amiretrorepvec; Flucytosine

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Cytosine; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3+3 dose escalation design with expansion at recommended Phase 2 dose.

Study Record Dates

• First Submitted: August 30, 2019
• First Posted: September 13, 2019
• Study Start: December 1, 2019
• Primary Completion: January 1, 2022
• Study Completion (Estimated): January 1, 2027
• Last Updated: March 30, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share