Study of a Retroviral Replicating Vector Combined With a Prodrug to Treat Patients Undergoing Surgery for a Recurrent Malignant Brain Tumor
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ClinicalTrials.gov Identifier: NCT01470794 |
Recruitment Status :
Completed
First Posted : November 11, 2011
Last Update Posted : May 21, 2018
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Glioblastoma Multiforme Anaplastic Astrocytoma Anaplastic Oligodendroglioma Anaplastic Oligoastrocytoma | Biological: Toca 511 vector Drug: Toca FC | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 58 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1 Ascending Dose Trial of Safety and Tolerability of Toca 511, a Retroviral Replicating Vector, Administered to Subjects at the Time of Resection for Recurrent High Grade Glioma & Followed by Treatment With Toca FC, Extended-Release 5-FC |
Actual Study Start Date : | February 2012 |
Actual Primary Completion Date : | April 12, 2016 |
Actual Study Completion Date : | April 12, 2016 |

Arm | Intervention/treatment |
---|---|
Experimental: Single Arm
Toca 511 vector/Toca FC prodrug
|
Biological: Toca 511 vector
All patients will receive Toca 511, a retroviral replicating vector that expresses the cytosine deaminase (CD) gene. CD converts the antifungal 5-FC to the anti-cancer drug 5-FU in cells that have been infected by the Toca 511 vector. Beginning approximately 6 weeks after administration of Toca 511, patients will begin courses of oral Toca FC at pre-specified intervals, depending on cohort, during the approximately 30 week study.
Other Names:
Drug: Toca FC Other Name: flucytosine, 5-FC, 5-FC XR, Toca FC |
- Dose Limiting Toxicities [ Time Frame: 2 months ]Excluding nausea, vomiting and fatigue, any Grade 3 or higher non-hematologic toxicity or any Grade 4 or higher hematologic toxicity, felt to be related to Toca 511 or the Toca 511/Toca FC combination.
- Overall Survival of Subjects [ Time Frame: Overall survival, Overall survival at 6 months (OS6), 9 months (OS9), and 12 months (OS12) ]
- Progression Free Survival (PFS) of Subjects [ Time Frame: PFS of subjects at 6 months (PFS-6) ]

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Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria (must all be answered "Yes"):
- Has the patient given written informed consent?
- Is the patient between 18 years old and 80 years old inclusive?
- Has the patient had histologically proven HGG with recurrence or progression following initial definitive therapy(s) such as surgery with or without adjuvant radiation therapy and/or chemotherapy (confirmed by diagnostic biopsy or contrast-enhanced MRI and evaluable by Macdonald criteria)? Note if first recurrence of GBM is documented by MRI, an interval of at least 12 weeks after the end of prior radiation therapy is required unless there is either: i) histopathologic confirmation of recurrent tumor, or ii) new enhancement on MRI outside of the radiotherapy treatment field.
- Does the patient have a single, HGG tumor recurrence/progression that is ≤ 5 cm in its greatest dimension?
- Based on the pre-operative evaluation, is the tumor recurrence/progression a candidate for ≥ 80% resection?
- Has the patient elected not to undergo treatment with the Gliadel® wafer?
- Does the patient have a Karnofsky performance status ≥ 70?
- Does the patient have an absolute neutrophil count (ANC) ≥ 1500/mm3?
- Does the patient have an absolute lymphocyte count ≥ 500/mm3?
- Does the patient have a platelet count ≥ 100,000/mm3?
- Does the patient have a Hgb ≥ 10 g/dL?
- Does the patient have a normal PT/PTT? (subnormal PT/PTT acceptable)
- Does the patient have an estimated glomerular filtration rate of at least 50 mL/min (inclusive) by the Cockcroft-Gault formula?
- Does the patient have an ALT < 3 times the upper limit of the laboratory reference range and total bilirubin < 1.5 mg/dL?
- If the patient is a female of childbearing potential, has she had a negative serum pregnancy test within the past 21 days?
- Is the patient willing to use condoms for contraception for 6 months after receiving Toca 511 or until there is no evidence of the virus in his/her blood, whichever is longer. If the patient is a fertile female, is she willing to use contraception for at least 12 months?
- Is the patient willing and able to abide by the protocol?
Exclusion Criteria (must all be answered "No"):
- Has the patient received cytotoxic chemotherapy within the past 3 weeks (6 weeks for nitrosoureas) of the planned surgery date?
- Does the patient have, or has the subject had, within the past 4 weeks any infection requiring antibiotic, antifungal or antiviral therapy?
- Has the patient had a surgical procedure in the last 28 days or a surgical wound that is not healed?
- Does the patient have any bleeding diathesis, or must the subject take any anticoagulants, or antiplatelet agents, including NSAIDs that cannot be stopped for surgery?
- Does the patient have a history of allergy or intolerance to flucytosine?
- Is the patient HIV positive?
- Does the patient have any gastrointestinal disease that would prevent him or her from being able to ingest or absorb flucytosine?
- Has the patient received any investigational treatment within the past 30 days?
- Is the patient breast feeding?
- Has the patient received Avastin® (bevacizumab) for this recurrence/progression, or within the past 5 weeks?
- Does the patient have a history of prior malignancy, excluding basal or squamous cell carcinoma of the skin, with an expected survival of less than five years?

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01470794
United States, California | |
UCLA | |
Los Angeles, California, United States, 90095 | |
University of California at San Diego | |
San Diego, California, United States, 92093 | |
United States, Michigan | |
Henry Ford Hospital | |
Detroit, Michigan, United States, 48202 | |
United States, New Jersey | |
JFK Medical Center | |
Edison, New Jersey, United States, 08820 | |
Hackensack University Medical Center | |
Hackensack, New Jersey, United States, 07601 | |
United States, Ohio | |
Cleveland Clinic Foundation | |
Cleveland, Ohio, United States, 44195 | |
Ohio State University | |
Columbus, Ohio, United States, 43210 | |
United States, Washington | |
Swedish Neuroscience Institute | |
Seattle, Washington, United States, 98122 |
Study Director: | Asha Das, MD | Tocagen Inc. | |
Principal Investigator: | Timothy Cloughesy, MD, NO | University of California, Los Angeles |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Tocagen Inc. |
ClinicalTrials.gov Identifier: | NCT01470794 |
Other Study ID Numbers: |
Tg 511-11-01 |
First Posted: | November 11, 2011 Key Record Dates |
Last Update Posted: | May 21, 2018 |
Last Verified: | May 2018 |
GBM HGG High grade glioma Malignant glioma Grade III glioma Grad IV glioma glioma glioblastoma |
Grade IV astrocytoma brain cancer recurrent glioblastoma AA AOD anaplastic astrocytoma Anaplastic oligodendroglioma Anaplastic oligoastrocytoma |
Glioblastoma Astrocytoma Oligodendroglioma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type |
Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Flucytosine Antifungal Agents Anti-Infective Agents Antimetabolites Molecular Mechanisms of Pharmacological Action |