A Study of the Safety of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Subjects With Newly Diagnosed High Grade Glioma Receiving Standard of Care

NCT02598011 | Withdrawn Phase 1

• 1 other identifier: Tg 511-15-03
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multi-center, open label trial of combination therapy with Toca 511 and ascending doses of Toca FC added to the SOC for newly diagnosed HGG.

Conditions

Newly Diagnosed High Grade Glioma (HGG)

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicities

  Number of participants with treatment-related adverse events as assessed by CTCAE v4.felt to be related to Toca 511 or the Toca 511/5-FC combination

  12 weeks

Study Arms (2)

Toca 511/Toca FC at 170 mg/kg/day

EXPERIMENTAL

Toca 511: 4 mL administered by intracranial parenchymal injection into the walls of the resection cavity following tumor resection or, for those subjects who are not candidates for resection, via stereotactic injection into their tumor using a standard Nashold-type side cutting biopsy needle. Toca FC: Approximately 4 to 6 weeks after tumor resection, subjects will begin temozolomide concurrent with radiation therapy. During concurrent chemoradiation at the start of the second and sixth week of concurrent chemoradiation and every 28 days thereafter, a 7-day course of oral Toca FC will be dosed at 170 mg/kg/day

Biological: Toca 511; Drug: Toca FC

Toca 511/Toca FC at 220 mg/kg/day

EXPERIMENTAL

Toca 511: 4 mL administered by intracranial parenchymal injection into the walls of the resection cavity following tumor resection or, for those subjects who are not candidates for resection, via stereotactic injection into their tumor using a standard Nashold-type side cutting biopsy needle. Toca FC: Approximately 4 to 6 weeks after tumor resection, subjects will begin temozolomide concurrent with radiation therapy. During concurrent chemoradiation at the start of the second and sixth week of concurrent chemoradiation and every 28 days thereafter, a 7-day course of oral Toca FC will be dosed at 220 mg/kg/day

Biological: Toca 511; Drug: Toca FC

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 5-flurocytosine (5FC) to the anticancer drug 5-FU in cells that have been infected by the Toca 511 vector

Also known as: vocimagene amiretrorepvec, RRV, retroviral replicating viral

Toca 511/Toca FC at 170 mg/kg/day; Toca 511/Toca FC at 220 mg/kg/day

Toca FC DRUG

Toca FC is an extended-release formulation of flucytosine. Toca FC is supplied as 500 mg white, oblong tablets with "TOCA FC" embossed on one side and "500" embossed on the other side

Also known as: Flucytosine, 5-FC, 5-Fluorocytosine

Toca 511/Toca FC at 170 mg/kg/day; Toca 511/Toca FC at 220 mg/kg/day

Eligibility Criteria

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

You may qualify if:

• Subject has given written informed consent
• Subject is at least 18 years old
• Subjects must have presumed newly diagnosed high grade glioma prior to tissue diagnosis or definitive initial surgical resection
• Based on the pre-operative evaluation by neurosurgeon, the subject is a candidate for planned resection of enhancing region of tumor OR for those subjects who are not candidates for resection, based on the pre-operative evaluation by neurosurgeon, the subject has a presumed newly diagnosed high grade glioma accessible by a technically feasible stereotactic trajectory
• Laboratory values adequate for subject to undergo surgery, including:
• Platelet count ≥ 100,000/mm3
• Hgb ≥ 10 g/dL
• Absolute neutrophil count (ANC) ≥ 1,500/mm3
• Normal PT/PTT (subnormal PT/PTT acceptable)
• Adequate liver function, including total bilirubin ≤ 1.5 x ULN (unless known Gilbert's syndrome); ALT ≤ 2.5 x ULN
• The subject has a KPS ≥ 70
• Women of childbearing potential (≥12 months of non-therapy-induced amenorrhea or surgically sterile) must have had a negative serum pregnancy test within the past 21 days and must use a birth control method in addition to barrier methods (condoms)
• Subject or subject's partner is willing to use condoms for 12 months after receiving Toca 511 or until there is no evidence of the virus in his/her blood, whichever is longer
• Subject has an absolute lymphocyte count (ALC) ≥ 500/mm3
• Estimated glomerular filtration rate of at least 50 mL/min by the Cockcroft Gault formula

You may not qualify if:

• History of other malignancy, unless the subject 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 localized prostate carcinoma or cervical carcinoma in situ after curative treatment
• A contrast enhancing brain tumor that is any of the following:
• Multi focal (defined as 2 separate areas of contrast enhancement measuring at least 1 cm in 2 planes that are not contiguous on either fluid attenuated inversion recovery (FLAIR) or T2 sequences);
• Associated with either diffuse subependymal or leptomeningeal dissemination; or \> 5 cm in any dimension
• Location in the brainstem, cerebellum or spinal cord
• Expansion Cohort:
• OR For those subjects who are not candidates for resection, injection of the tumor requires violation of the ventricular system
• The subject has or had any active infection requiring antibiotic, antifungal or antiviral therapy within the past 4 weeks
• The subject has any bleeding diathesis, or must take anticoagulants, or antiplatelet agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), at the time of the scheduled surgery that cannot be stopped for surgery
• The subject received any investigational treatment for any reason within the past 30 days. Investigational agents used to improve surgical resection or craniotomy wound healing or recovery are allowed.
• The subject intends to undergo treatment with the Gliadel® wafer at the time of this surgery
• Prior intracranial gamma knife, stereotactic radiosurgery, or other focal high-dose radiotherapy is not allowed
• Severe pulmonary, cardiac or other systemic disease, specifically:
• New York Heart Association \> Grade 2 congestive heart failure within 6 months prior to study entry, unless asymptomatic and well controlled with medication (see Appendix G)
• Uncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades des pointes), clinically significant pulmonary disease (such as ≥ Grade 2 dyspnea, according to CTCAE 4.03)

Sponsors & Collaborators

• Tocagen Inc.: lead

MeSH Terms

Interventions

vocimagene amiretrorepvec; Flucytosine

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2015
• First Posted: November 5, 2015
• Study Start: January 1, 2017
• Primary Completion: November 1, 2022
• Last Updated: March 30, 2020

Record last verified: 2015-12