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Bladder CancerPhase 1NCT04089163

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

A Phase 1 study testing Toca 511 and Toca FC (extended-release formulation of flucytosine) in people with Bladder Cancer, run by Tocagen Inc..

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bladder Cancer
What is being tested?
Toca 511 and Toca FC (extended-release formulation of flucytosine)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Dec 2019to Jan 2027
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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
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  • 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

About this study

Official title: Toca 8: A Multicenter, Open-Label, Phase 1 Study to Evaluate the Safety and Tolerability of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Patients With Recurrent High Grade Non-Muscle Invasive Bladder Cancer

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
Being tested
Toca 511, Toca FC (extended-release formulation of flucytosine)
Keywords
non-muscle invasive bladder cancer, bladder cancer, high grade non-muscle invasive bladder cancer, HG NMIBC, NMIBC, high grade NMIBC
Medical subject headings
Urinary Bladder Neoplasms, Non-Muscle Invasive Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Toca 511Biological

    Also called vocimagene amiretrorepvec, retroviral replicating vector (RRV)

    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.

  • Toca FC (extended-release formulation of flucytosine)Drug

    Also called flucytosine, 5-fluorocytosine (5-FC)

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

Study groups in NCT04089163
Study groupRoleWhat they receive
Sequential Dose CohortsExperimentalDoses 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.
Receives: Biological: Toca 511; Drug: Toca FC (extended-release formulation of flucytosine)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 5 weeks

Secondary outcomes (2)

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

    Measured: 3 weeks (+/- 1 week)

  2. 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)

    Measured: 1 week for plasma, 4 weeks for urine

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Sep 2019
  2. Study startDec 2019 (estimated)
  3. Primary completionJan 2022 (estimated)
  4. Study completionJan 2027 (estimated)

Why it stopped: Sponsor decision.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Intervention model
Sequential
Model description
3+3 dose escalation design with expansion at recommended Phase 2 dose.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04089163
Sponsor's protocol ID
Tg 511-19-01
Status last verified
Mar 2020
First submitted
30 Aug 2019
Last updated
30 Mar 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Toca 511 and Toca FC (extended-release formulation of flucytosine) in people with Bladder Cancer, run by Tocagen Inc..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 30 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicities (time frame: 5 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04089163.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2020.

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