Neural Stem Cell Virotherapy for Brain Cancer

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Radiation, Chemotherapy, Investigational agents

Disqualifiers: Viral infections, Bleeding disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 4 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for people with glioblastoma, a type of brain cancer that has returned after treatment. The treatment, called NSC-CRAd-S-pk7 (a neural stem cell virotherapy), uses special stem cells carrying a virus to target and kill cancer cells. Researchers aim to determine if administering multiple doses of this treatment directly into the brain is safe and effective. People whose glioblastoma has returned after treatments like radiation and chemotherapy, and who require surgery, may be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that NSC-CRAd-S-pk7 is a promising and safe treatment for glioblastoma, a type of brain cancer. In earlier studies, patients who received this treatment tolerated it well. The research demonstrated that using special stem cells to deliver a virus directly to cancer cells is both feasible and safe. These stem cells target and destroy tumor cells without significantly harming healthy cells.

While more research is needed to understand all possible side effects, the initial results are encouraging. The treatment involves injecting doses directly into the brain, which has been done safely in previous trials. This suggests that NSC-CRAd-S-pk7 could be a promising option for people with recurring glioblastoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain cancer, which often include surgery, radiation, and chemotherapy, NSC-CRAd-S-pk7 offers a novel approach by using neural stem cells to deliver a cancer-killing virus directly to the tumor site. This treatment is unique because it injects the virus-laden stem cells into the brain during surgery, allowing for targeted therapy that potentially minimizes damage to healthy tissue. Researchers are excited about this treatment as it promises a new mechanism of action by combining stem cell therapy with virotherapy, which could offer a more effective and less invasive option for patients compared to conventional methods.

What evidence suggests that NSC-CRAd-S-pk7 might be an effective treatment for glioblastoma?

Research has shown that NSC-CRAd-S-pk7, which participants in this trial will receive, may help treat glioblastoma, a type of brain cancer. In studies with mice, this treatment increased survival time by up to 50% compared to those treated with only the virus. NSC-CRAd-S-pk7 uses special brain cells to deliver a virus directly to the tumor, allowing the virus to attack and possibly kill cancer cells. The treatment also alters genes that help control inflammation, potentially enhancing its ability to fight cancer. These findings suggest that NSC-CRAd-S-pk7 could be effective for patients with glioblastoma. ^{1 2 3 5 6}

Who Is on the Research Team?

Jana L Portnow, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• NSC-CRAd-S-pk7
• Resection

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.

How Is the Trial Designed?

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

Patients undergo standard surgical resection, and during surgery the first dose of study agent is injected into the wall of the resection cavity. Patients then receive three additional doses every week or every two weeks (depending on when they enroll in the study) via a catheter that was placed during surgery

NSC-CRAd-S-pk7 is already approved in United States for the following indications:

Approved in United States as NSC-CRAd-S-pk7 for:

• Recurrent High-Grade Gliomas

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05139056

NCT05139056 | Multiple Intracerebral Doses of Neural ... This phase I trial studies the safety of giving multiple intracerebral doses of NSC-CRAd-S-pk7 to treat patients with glioblastoma at first recurrence.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8328944/

Neural Stem Cell Delivery of an Oncolytic Adenovirus in ... Preclinical work showed that NSC-CRAd-S-pk7 increased median survival by up to 50% compared to mice that were treated by the oncolytic virus ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-10170

Neural Stem Cell Therapy (NSC-CRAd-S-pk7) for the ... This phase I trial tests the safety, side effects, and best treatment schedule of neural stem cells-expressing CRAd-S-pk7 (NSC-CRAd-S-pk7) in treating patients ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1525001616327575

Neural Stem Cell-based Cell Carriers Enhance ... Taken together, these results indicate that loading of CRAd-S-pk7 into NSCs leads to the expression of both pro- and anti-inflammatory genes and decreases ...

5. clinicaltrials.stanford.edu clinicaltrials.stanford.edu/trials/m/NCT05139056.html

Multiple Intracerebral Doses of Neural Stem Cell-Based ... This phase I trial studies the safety of giving multiple intracerebral doses of NSC-CRAd-S-pk7 to treat patients with glioblastoma at first recurrence.

6. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00245-X/abstract

Neural stem cell delivery of an oncolytic adenovirus in ... NSC-CRAd-S-pk7 treatment was feasible and safe. Our immunological and histopathological findings support continued investigation of NSC-CRAd-S- ...