Glioma, Malignant, New Diagnosis Tumor
Conditions
Keywords
Virotherapy, NSC-CRAd-S-pk7
Brief summary
The goal of this clinical trial is to learn about the safety and feasibility of administering repeated doses of neural stem cell (NSC)-conditionally replicative adenovirus (CRAd)-survivin (S)-protomer (p)k7, in persons with newly diagnosed high grade glioma. The main questions it aims to answer are: * whether multiple doses of NSC-CRAd-S-pk7 are safe and feasible * how multiple doses of NSC-CRAd-S-pk7 influence tumor response, overall survival, time to tumor progression, and quality of life. Participants will: * undergo a biopsy to confirm high grade glioma, then receive the first dose of NSC-CRAd-S-pk7 into the brain * about 2 weeks later, undergo surgery to remove the tumor and receive the second dose of NSC-CRAd-S-pk7 into the brain * start chemoradiation about 2 weeks after surgery, then about 2 weeks later, receive the 3rd dose of NSC-CRAd-S-pk7 into the brain * four weeks later, at the end of chemoradiation, receive a fourth dose of NSC-CRAd-S-pk7 into the brain. * after radiation is finished, receive standard of care chemotherapy and tumor-treating fields. Two additional doses of NSC-CRAd-S-pk7 will be given every 4 weeks.
Detailed description
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). 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®). NSC-CRAd-S-pk7 doses #5 and #6 will be administered concurrently (± 3 days) with adjuvant cycle 1 and 2 of TMZ.
Interventions
BIOLOGICALNSC-CRAd-S-pk7
NSC-CRAd-S-pk7 1·50 x 10⁸ NSCs loaded with1·875 x viral particles administered intra-tumorally on Day 0 and Day 15, then every 4 weeks for up to 6 total doses.
Sponsors
Northwestern University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Study participants will receive up to 6 doses of NSC-CRAd-S-pk7 in addition to standard of care radiation and temozolomide.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity of repeat NSC-CRAd-S-pk7 dosing | 8 weeks | Determination of the dose limiting toxicity of repeated dosing of NSC-CRAd-S-pk7 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response to therapy | 5 years | Objective response to therapy as determined by Immune Response Assessment in Neuro-Oncology (iRANO) criteria |
| Overall survival | 5 years | Overall survival time from the first study product injection to death |
| Progression-free survival | 18 months | Time from the first study product injection to first confirmed disease progression as determined by objective tumor response |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRoger Stupp, MD
Northwestern University
Outcome results
None listed