- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02598011
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 (Toca7)
The Toca 7 Study: A Phase 1b 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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Enrolled subjects with presumed newly diagnosed HGG will undergo planned resection of tumor.
Subjects with HGG will receive Toca 511, administered by intracranial parenchymal injection into the walls of the resection cavity.
This study will establish the recommended Phase 2 dose of Toca FC to be used in combination with standard of care chemoradiation and temozolomide in subjects with newly diagnosed HGG.
Subjects will begin chemoradiation treatment approximately 4 to 6 weeks after surgery. Oral Toca FC (7-day courses) will be administered concurrent with the start of the second and sixth weeks of chemoradiation during the concurrent treatment period, and concurrent with the start of temozolomide during the maintenance treatment period.
Study Type
Phase
- Phase 1
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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)
- Subjects who have any other disease, either metabolic or psychological, which as per Investigator assessment may affect the subject's compliance or place the subject at higher risk of potential treatment complications
- The subject is breast feeding
- The subject is HIV positive
- The subject has a history of allergy or intolerance to flucytosine
- The subject has a gastrointestinal disease that would prevent him or her from being able to swallow Toca FC tablets or absorb flucytosine
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Toca 511/Toca FC at 170 mg/kg/day
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 |
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
Other Names:
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
Other Names:
|
EXPERIMENTAL: Toca 511/Toca FC at 220 mg/kg/day
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 |
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
Other Names:
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
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose limiting toxicities
Time Frame: 12 weeks
|
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
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Glioma
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antimetabolites
- Antifungal Agents
- Flucytosine
Other Study ID Numbers
- Tg 511-15-03
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Newly Diagnosed High Grade Glioma (HGG)
-
James FelkerConnor's Cure; Ellie Kavalieros Fund; Translational Brain Tumor Research FundActive, not recruitingNewly Diagnosed Pediatric Pontine Glioma | Newly Diagnosed Pediatric High Grade Glioma | Recurrent Pediatric High Grade Glioma | Recurrent Pediatric Low Grade GliomaUnited States
-
Sidney Kimmel Comprehensive Cancer Center at Johns...Accelerate Brain Cancer CureCompletedNewly Diagnosed High-Grade GliomaUnited States
-
University of UtahCompletedNewly Diagnosed High Grade GliomaUnited States
-
University of Michigan Rogel Cancer CenterNational Cancer Institute (NCI)RecruitingRecurrent Glioblastoma | Newly Diagnosed Glioblastoma | Recurrent Gliosarcoma | Recurrent Astrocytoma, Grade IV | Newly Diagnosed Gliosarcoma | Newly Diagnosed Astrocytoma, Grade IVUnited States
-
Hospices Civils de LyonTerminatedLow Grade Glioma (LGG), High Grade Glioma (HGG)France
-
Saint John's Cancer InstituteCompletedNewly Diagnosed High Grade GliomaUnited States
-
Hospices Civils de LyonCompletedLow Grade Glioma (LGG) | High Grade Glioma (HGG)France
-
Aadi Bioscience, Inc.CompletedHigh Grade Recurrent Glioma and Newly Diagnosed GlioblastomaUnited States
-
Northern Sydney and Central Coast Area Health ServiceMerck KGaA, Darmstadt, GermanyUnknownNewly Diagnosed Non Methylated Glioblastoma Multiforme Grade 4Australia
-
Children's Hospital Medical Center, CincinnatiGenentech, Inc.CompletedDiffuse Intrinsic Pontine Glioma | Newly Diagnosed High-Grade GliomasUnited States
Clinical Trials on Toca 511
-
Tocagen Inc.CompletedGlioblastoma Multiforme | Anaplastic Oligoastrocytoma | Anaplastic Astrocytoma | Anaplastic OligodendrogliomaUnited States
-
Tocagen Inc.CompletedGlioblastoma | Anaplastic Oligoastrocytoma | Anaplastic Astrocytoma | Anaplastic OligodendrogliomaUnited States
-
Tocagen Inc.CompletedGlioblastoma Multiforme | Anaplastic Oligoastrocytoma | Anaplastic Astrocytoma | Anaplastic OligodendrogliomaUnited States
-
Tocagen Inc.TerminatedMelanoma | Sarcoma | Lymphoma | Head and Neck Cancer | Colorectal Cancer | Pancreatic Cancer | Ovarian Cancer | Non-Small Cell Lung Cancer | Bladder Cancer | Triple Negative Breast Cancer | IDH1 Mutated Solid Tumors | IDH1 Mutated or MGMT Methylated Recurrent HGG (Not Recruiting)United States
-
Tocagen Inc.Withdrawn
-
Tocagen Inc.TerminatedAstrocytoma | Glioblastoma Multiforme | Gliomas, MalignantUnited States
-
Tocagen Inc.TerminatedGlioblastoma Multiforme | Anaplastic AstrocytomaUnited States, Korea, Republic of, Canada, Israel
-
NRG OncologyNational Cancer Institute (NCI)WithdrawnGlioblastoma | Anaplastic Astrocytoma | Oligodendroglioma | Supratentorial Glioblastoma