Overview

Testing the Addition of an Anti-cancer Viral Gene Therapy, Toca 511/Toca FC, to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed Glioblastoma

Status:
Withdrawn
Trial end date:
2030-11-30
Target enrollment:
0
Participant gender:
All
Summary
This phase II/III trial studies how well vocimagene amiretrorepvec (Toca 511) and extended release flucytosine (Toca FC) work when added to the usual treatment (temozolomide and radiation therapy) in treating patients with newly diagnosed glioblastoma. Toca 511 is a live virus that has been built to carry a gene into tumor cells. This gene carries instructions that cause the tumor cells to turn Toca FC, typically used to treat fungal infections, into a drug that may kill the tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving Toca 511 and Toca FC in addition to the usual treatment (temozolomide and radiation therapy) may help shrink or stabilize cancer or extend the life of patients with newly diagnosed glioblastoma.
Phase:
Phase 2/Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
NRG Oncology
Collaborator:
National Cancer Institute (NCI)
Treatments:
Flucytosine
Temozolomide
Criteria
Inclusion Criteria:

- Presumptive diagnosis of glioblastoma based on magnetic resonance imaging (MRI)
imaging within 14 days prior to registration.

- NOTE: Patients who undergo treatment with Toca 511 whose final pathology shows
diagnosis other than glioblastoma (e.g. anaplastic astrocytoma or
oligodendroglioma or any other histology) will be treated with Toca FC and
chemoradiation; however they will not be analyzed in the primary endpoint. The
outcomes of these patients will be reported descriptively. Similarly the patients
with anaplastic astrocytoma or oligodendroglioma or any other histology treated
on the standard-of-care arm will be reported separately and they are allowed to
receive the treatment per choice of the treating physician/ investigator (for
e.g. radiation therapy [RT] plus temozolomide or RT plus
procarbazine-lomustine-vincristine [PCV])

- In addition, patients who have undergone biopsy with diagnosis of glioblastoma and who
have never received any chemotherapy and/or radiation and are candidates for >= 80%
resection of enhancing region are eligible

- The tumor must be unifocal, confined to the supratentorial compartment and based on
the pre-operative evaluation, the patient is a candidate for >= 80% resection of
enhancing region

- Measurable disease preoperatively, defined as at least 1 contrast enhancing lesion,
with 2 perpendicular measurements of at least 1 cm, as per Response Assessment in
Neuro-Oncology (RANO) criteria

- The hematoxylin and eosin (H&E) slide and formalin-fixed paraffin-embedded (FFPE)
tumor tissue block must be available to be sent for mandatory central pathology review
after registration

- Patients must be able to undergo an evaluation by MRI within 96 hours post surgery to
assess extent of resection

- Karnofsky performance status >= 70 within 14 days prior to registration

- History/physical examination within 14 days prior to registration

- Platelet count >= 100,000/mm^3 (within 14 days prior to registration)

- Hemoglobin (Hgb) >= 10 g/dL (within 14 days prior to registration)

- Absolute neutrophil count (ANC) >= 1,500/mm^3 (within 14 days prior to registration)

- Absolute lymphocyte count (ALC) >= 1000/mm^3 (within 14 days prior to registration)

- Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless has Gilbert?s syndrome)
(within 14 days prior to registration)

- Alanine aminotransferase (ALT) =< 2.5 x ULN (within 14 days prior to registration)

- Estimated glomerular filtration rate of at least 50 mL/min by the Cockcroft Gault
formula (within 14 days prior to registration)

- Women of childbearing potential (women who have not had >=12 months of non therapy
induced amenorrhea or are not surgically sterile) must have had a negative serum
pregnancy test within 14 days prior to registration and must agree to use a birth
control method in addition to barrier methods (condoms or diaphragm) during treatment
with temozolomide

- If the patient is randomized to arm 2, the patient or patient?s partner must be
willing to use barrier method of contraception for 12 months after receiving Toca 511
and 1 month after stopping Toca FC or until there is no evidence of the virus in the
patient?s blood, whichever is longer

- The patient or a legally authorized representative must provide study-specific
informed consent prior to registration

Exclusion Criteria:

- History of prior invasive malignancy (except non-melanomatous skin cancer) unless
disease free for a minimum of 3 years

- A contrast enhancing brain tumor on MRI that is any of the following:

- Multi focal (defined as 2 separate areas of contrast enhancement measuring at
least 10 mm in 2 planes that are not contiguous on either fluid attenuated
inversion recovery [FLAIR] or T2 hyperintensity);

- Associated with either diffuse subependymal or leptomeningeal dissemination; or

- > 50 mm in any dimension

- Active infection (excluding skin or toenail infections) requiring systemic antibiotic,
antifungal or antiviral therapy within 28 days prior to registration

- Bleeding diathesis, or must take anticoagulants, or antiplatelet agents, including
nonsteroidal anti inflammatory drugs (NSAIDs), at the time of the scheduled resection
that cannot be stopped for surgery

- Known human immunodeficiency virus (HIV) positive status

- History of allergy or intolerance to flucytosine

- Swallowing difficulty that would prevent patient from being able to swallow either
temozolomide or Toca FC or severe active mal-absorption

- Patients who are breast feeding or lactating

- Intent to undergo treatment with the Gliadel wafer at the time of this surgery or has
received the Gliadel

- Prior to registration, steroid treatment beyond a maximum of 8 mg/day of dexamethasone
(or equivalent) or a total of 8 weeks (56 days) is excluded

- Severe pulmonary, cardiac or other systemic disease, specifically:

- New York Heart Association > =Class II congestive heart failure within 6 months
(180 days) prior to registration, unless asymptomatic and well controlled with
medication

- 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 disease that as per investigator assessment may affect the patient?s
compliance or place the patient at higher risk of potential treatment
complications