Newly Diagnosed High Grade Glioma (HGG)Phase 1Toca7NCT02598011

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

A Phase 1 study testing Toca 511 and Toca FC in people with Newly Diagnosed High Grade Glioma (HGG), run by Tocagen Inc..

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Newly Diagnosed High Grade Glioma (HGG)
What is being tested?: Toca 511 and Toca FC
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: No sites listed yet
Study dates: Jan 2017to Nov 2022
Phase: Phase 1

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

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

Show all 15Show fewer

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

Who cannot join

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:

Show all 20Show fewer

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

About this study

Official title: 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

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.

Read the 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.

Conditions: Newly Diagnosed High Grade Glioma (HGG)
Being tested: Toca 511, Toca FC

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, RRV, retroviral replicating viral
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
Toca FCDrug
Also called Flucytosine, 5-FC, 5-Fluorocytosine
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

Study groups in NCT02598011
Study group	Role	What they receive
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 Receives: 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 Receives: Biological: Toca 511; Drug: Toca FC

What is being measured

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

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
Measured: 12 weeks

Timeline

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

Jan 2017Nov 2022

First posted5 Nov 2015 (estimated)
Study startJan 2017
Primary completionNov 2022 (estimated)

Why it stopped: Sponsor decision

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Newly Diagnosed High Grade Glioma (HGG)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02598011
Sponsor's protocol ID: Tg 511-15-03
Acronym: Toca7
Status last verified: Dec 2015
First submitted: 3 Nov 2015
Last updated: 30 Mar 2020
Results posted: No