Neural Stem Cell Virotherapy for Brain Cancer

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: City of Hope Medical Center

Must not be taking: Radiation, Chemotherapy, Investigational agents

Disqualifiers: Viral infections, Bleeding disorder, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This phase I trial studies the effect of multiple doses of NSC-CRAd-S-pk7 in treating patients with high-grade gliomas that have come back (recurrent). NSC-CRAd-S-pk7 consists of neural stem cells that carry a virus, which can kill cancer cells. Giving multiple doses of NSC-CRAd-S-pk7 may kill more tumor cells.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does require certain time intervals since your last chemotherapy or targeted therapy. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment NSC-CRAd-S-pk7 for brain cancer?

Research shows that using neural stem cells to deliver the oncolytic virus CRAd-S-pk7 can significantly improve survival rates in animal models of glioma, a type of brain cancer. The treatment enhances the virus's ability to target and destroy cancer cells, increasing survival by about 50% compared to the virus alone. ^{1 2 3 4 5}

Is Neural Stem Cell Virotherapy for Brain Cancer safe for humans?

Research shows that Neural Stem Cell Virotherapy, using NSC-CRAd-S-pk7, has been tested in humans with brain cancer and appears to have minimal systemic toxicity, meaning it doesn't cause widespread harm in the body. In animal studies, the treatment was well-tolerated, with the virus staying mostly in the targeted brain area and not spreading to other organs. ^{1 2 3 4 5}

How is the treatment NSC-CRAd-S-pk7 different from other brain cancer treatments?

NSC-CRAd-S-pk7 is unique because it uses neural stem cells to deliver an oncolytic virus directly to brain tumors, enhancing the virus's ability to target and destroy cancer cells while minimizing damage to healthy tissue. This approach leverages the natural tumor-seeking properties of neural stem cells, which helps improve the distribution and effectiveness of the virus compared to traditional methods. ^{1 2 3 4 5}

Research Team

Jana Portnow, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults with high-grade gliomas that have returned after treatment. Candidates must have adequate blood counts, organ function, and be at least 6 weeks past certain chemotherapies. They need surgery for tumor resection, not be pregnant or breastfeeding, use contraception if applicable, and cannot have specific HLA antibodies or active CNS infections.

Inclusion Criteria

At least 6 weeks must have elapsed since taking a nitrosourea-containing chemotherapy regimen

You must stop taking any targeted medication for at least 2 weeks before participating in the study.

All participants must have the ability to understand and the willingness to sign a written informed consent

Exclusion Criteria

You are currently pregnant or breastfeeding.

Patient has chronic or active viral infections of the central nervous system (CNS)

Patient has a coagulopathy or bleeding disorder

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Resection

Patients undergo standard of care surgical resection

1 week

1 visit (in-person)

Treatment

Patients receive NSC-CRAd-S-pk7 intracerebrally over 10 minutes once weekly for up to 4 doses

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

2 visits (in-person) at 3 and 6 months, then annually

Treatment Details

Interventions

• NSC-CRAd-S-pk7 (Virus Therapy)
• Resection (Surgery)

Trial Overview The trial tests multiple doses of NSC-CRAd-S-pk7 on patients with recurrent high-grade gliomas. This therapy uses neural stem cells carrying a virus to target and kill cancer cells during the patient's surgery for tumor resection.

Participant Groups

Group I: Treatment (NSC-CRAd-S-pk7) Experimental Treatment 2 Interventions

Patients undergo standard of care surgical resection. Patients then receive NSC-CRAd-S-pk7 intracerebrally over 10 minutes QW for up to 4 doses in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The trial involving 12 patients with newly diagnosed high-grade gliomas demonstrated that NSC-CRAd-S-pk7, an engineered oncolytic adenovirus delivered by neural stem cells, was safe with no formal dose-limiting toxicity, although one patient experienced viral meningitis due to an injection error.

The treatment showed promising efficacy with a median progression-free survival of 9.1 months and a median overall survival of 18.4 months, suggesting that NSC-CRAd-S-pk7 warrants further investigation in phase 2/3 clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural stem cell delivery of an oncolytic adenovirus in newly diagnosed malignant glioma: a first-in-human, phase 1, dose-escalation trial. Fares, J., Ahmed, AU., Ulasov, IV., et al.[2022]

Neural stem cells (NSCs) can effectively deliver a conditionally replicating adenovirus (CRAd) to glioma cells, enhancing the distribution of the oncolytic vector within tumors.

The study identified the CRAd-Survivin (S)-pk7 as the most effective vector for NSC-mediated delivery, demonstrating that NSCs improve the targeting of the virus to glioma cells compared to direct virus injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural stem cells target intracranial glioma to deliver an oncolytic adenovirus in vivo. Tyler, MA., Ulasov, IV., Sonabend, AM., et al.[2023]

The study demonstrates that neural stem cells (NSCs) can effectively deliver the oncolytic adenovirus CRAd-S-pk7 to glioma cells, replicating and releasing the virus to target tumors specifically, which enhances treatment efficacy.

Using NSCs as carriers minimizes the spread of the virus to non-target areas in the brain and shows minimal systemic toxicity, making this approach a promising strategy for optimizing oncolytic virotherapy for glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic study of neural stem cell-based cell carrier for oncolytic virotherapy: targeted delivery of the therapeutic payload in an orthotopic brain tumor model. Thaci, B., Ahmed, AU., Ulasov, IV., et al.[2021]

The study demonstrates that neural stem cells (NSCs) loaded with the oncolytic virus CRAd-Survivin-pk7 can effectively deliver the virus to glioblastoma tumors, enhancing median survival in mice by approximately 46% when combined with standard treatments like radiation and temozolomide.

Timing is crucial; administering the OV-loaded NSCs before radiation and chemotherapy significantly extends survival by 30%, highlighting the importance of treatment sequencing in improving outcomes for glioblastoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The timing of neural stem cell-based virotherapy is critical for optimal therapeutic efficacy when applied with radiation and chemotherapy for the treatment of glioblastoma. Tobias, AL., Thaci, B., Auffinger, B., et al.[2021]

Using neural stem cells (NSCs) to deliver the oncolytic adenovirus CRAd-S-pk7 directly into gliomas significantly improved median survival by approximately 50% compared to using the virus alone, based on an orthotopic xenograft model.

The study found that oncolytic virus infection enhances the migratory ability of NSCs and upregulates chemoattractant receptors, suggesting that NSCs can effectively target tumors while protecting the virus from the immune system, thereby improving treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural stem cell-based cell carriers enhance therapeutic efficacy of an oncolytic adenovirus in an orthotopic mouse model of human glioblastoma. Ahmed, AU., Thaci, B., Alexiades, NG., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Neural stem cell delivery of an oncolytic adenovirus in newly diagnosed malignant glioma: a first-in-human, phase 1, dose-escalation trial. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Neural stem cells target intracranial glioma to deliver an oncolytic adenovirus in vivo. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetic study of neural stem cell-based cell carrier for oncolytic virotherapy: targeted delivery of the therapeutic payload in an orthotopic brain tumor model. [2021]

4. England pubmed.ncbi.nlm.nih.gov

The timing of neural stem cell-based virotherapy is critical for optimal therapeutic efficacy when applied with radiation and chemotherapy for the treatment of glioblastoma. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Neural stem cell-based cell carriers enhance therapeutic efficacy of an oncolytic adenovirus in an orthotopic mouse model of human glioblastoma. [2023]