Clinical Trial Finder

Inclusion Criteria:

• - Diagnosis of a high-grade glioma (WHO grade 3 or grade 4).

• - Patients must have presumed high grade glioma (WHO grade 3 or 4) based on clinical and radiologic evaluation for registration.

• - A pathologic confirmation of high grade glioma must be made at the time of stereotactic biopsy prior to NSC-CRAd-S-pk7 injection; if this is not possible, the injection will not be performed and the subject will no longer be eligible for the study).

• - Tumor must be accessible for injection and must not be located in the brainstem or contained within the ventricular system.

• - Planning to undergo standard radiation/chemotherapy.

• - 18 years of age or older.

• - Performance status (PS) must be WHO PS of < 2.

• - Stable or decreasing dose of corticosteroids equivalent to ≤ 6 mg/day for the 5 days prior to inclusion.

• - Serum glutamic-oxaloacetic transaminase (SGOT or AST) < 3x upper limit of normal.

• - Serum creatinine < 2mg/dl.

• - Platelets > 100,000/mm3 and white blood cells (WBCs) > 3000/mm3.

Exclusion Criteria:

• - Prior or ongoing liver disease including known cirrhosis.

• - Known hepatitis B or C infection, known HIV infection.

• - Chronic use of immunosuppressive drugs (with exception of corticosteroids required for mass effect).

• - Acute viral, bacterial or fungal infections requiring therapy.

• - Pregnant or breast-feeding patients.

• - Evidence of metastatic disease or other malignancy (except squamous or basal cell skin cancers).

• - Prior radiation therapy to the brain or prior treatment for brain tumor.

The treatment regimen contains 3 phases: Surgical phase: Patients undergo a biopsy and upon intraoperative confirmation of high grade glioma, NSC-CRAd-S-pk7 dose #1 will be injected into the biopsy site. Patients will undergo resection of the tumor 14 (+/- 3) days later, administration of second dose of the investigational product (NSC-CRAd-S-pk7 dose #2), and implantation of the catheter system. The investigational product will then be given monthly for a total of 6 doses (see below). Every other patient enrolled (beginning with the first patient) will also undergo oral administration of NACA (an over-the-counter drug that acts as a free radical scavenger and improves NSC viability) starting at registration until the day prior to surgical tumor resection and planned investigational product injection #2. Radiotherapy phase: After recovery from surgery (usually within 2 weeks), standard chemoradiotherapy will be initiated consisting of daily radiotherapy (2 Gy per fraction x 30 fractions) and concomitant temozolomide (TMZ) chemotherapy (75 mg/m2 daily from day 1 of RT until last day of RT). About 10-14 days into radiotherapy (= approx. 4 weeks after intraoperative dose #2), patients will be receiving NSC-CRAd-S-pk7 dose #3 through the previously implanted catheter system. This also marks the beginning of the formal dose-limiting toxicity (DLT) period, as this virus' survivin gene promoter is activated by the concomitant irradiation. Four weeks later, ie. at the end of radiotherapy dose #4 is administered as previously, provided no DLT toxicity has been observed and viral treatment related toxicities have returned to grade ≤ 2. Adjuvant (also called maintenance) phase: As per standard of care, approx. 4 weeks after end of radiotherapy, patients will start maintenance TMZ chemotherapy (150

• - 200 mg/m2, daily x 5 every 28 days) and loco-regional treatment with alternating Tumor Treating Fields (TTFields, Optune®).

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