Stem Cell Therapy + Chemotherapy for Brain Tumor

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors

Disqualifiers: HIV, Hepatitis C, Active infection, others

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

Compensation: Varies

Number of Visits: 1

Duration: 28 days per cycle

18 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting treatment. You must stop using specific drugs, such as certain anticonvulsants, CYP3A4 inhibitors, UGT1A1 inhibitors, and herbal medications, at least 2 weeks before the trial begins. It's best to discuss your current medications with the trial team to see if any need to be paused.

What data supports the effectiveness of the treatment Stem Cell Therapy + Chemotherapy for Brain Tumor?

Research shows that using neural stem cells to deliver enzymes that activate the drug irinotecan (CPT-11) can effectively target brain tumors, increasing the drug's potency and reducing tumor growth in preclinical models. This approach has shown promise in treating various cancers, including brain tumors, by enhancing the conversion of irinotecan to its active form, SN-38, directly at the tumor site. ^{1 2 3 4 5}

Is the combination of stem cell therapy and chemotherapy safe for treating brain tumors?

Research shows that using neural stem cells to deliver chemotherapy drugs like irinotecan (CPT-11) to brain tumors can help target the tumor more effectively and reduce side effects. This approach has been tested in animal models and shows promise for being safe, but more studies are needed to confirm its safety in humans. ^{1 2 3 4 5}

How is the stem cell therapy with irinotecan different from other brain tumor treatments?

This treatment is unique because it uses neural stem cells to deliver an enzyme that converts irinotecan into its active form directly at the tumor site, enhancing the drug's effectiveness while reducing side effects by targeting the tumor more precisely. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of carboxylesterase-expressing allogeneic neural stem cells when given together with irinotecan hydrochloride in treating patients with high-grade gliomas that have come back. Placing genetically modified neural stem cells into brain tumor cells may make the tumor more sensitive to irinotecan hydrochloride. Irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving carboxylesterase-expressing allogeneic neural stem cells and irinotecan hydrochloride may be a better treatment for high-grade gliomas.

Research Team

Jana L Portnow

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for patients with recurrent high-grade brain tumors like glioblastoma or astrocytoma, who have already tried standard treatments. They must be in good enough health to understand the study and undergo surgery, with a life expectancy of at least 3 months. Participants can't join if they've had neural stem cell therapy before, are on certain drugs that affect the treatment, or have infections like HIV.

Inclusion Criteria

Life expectancy of >= 3 months

Patient must be able to understand and be willing to sign a written informed consent document

Participant must be willing to comply with study and/or follow-up procedures

Exclusion Criteria

Diagnosis of Gilbert's disease

Pregnant women and women who are lactating

You are currently taking herbal medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive carboxylesterase-expressing allogeneic neural stem cells intracranially and irinotecan hydrochloride intravenously. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Visits on days 1, 3, 15, and 17 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups at 30 days, 3 and 6 months, and then annually for a minimum of 15 years.

15 years

Treatment Details

Interventions

• Carboxylesterase-expressing Allogeneic Neural Stem Cells
• Irinotecan

Trial Overview The trial tests genetically modified neural stem cells combined with irinotecan hydrochloride against high-grade gliomas. The goal is to see if this combo makes the cancer more sensitive to treatment and stops tumor growth by blocking key enzymes needed by cancer cells.

Participant Groups

Group I: Treatment (hCE1m6-NSCs and irinotecan hydrochloride) Experimental Treatment 5 Interventions

Patients receive carboxylesterase-expressing allogeneic neural stem cells intracranially over 1.5-4.5 hours on days 1 and 15 (day 1 only for patients at dose level 1) and irinotecan hydrochloride IV over 90 minutes on days 3 and 17. Cycles repeat every 28 days 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

Irinotecan (CPT-11) demonstrated activity in treating recurrent malignant gliomas, with 15% of patients showing a confirmed partial response and 55% achieving stable disease for over 12 weeks, based on a study of 60 patients.

The treatment was associated with limited toxicity, primarily mild side effects like neutropenia and nausea, but the low plasma concentrations of the drug suggest that concurrent use of anticonvulsants and dexamethasone may reduce its effectiveness by enhancing drug clearance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan therapy in adults with recurrent or progressive malignant glioma. Friedman, HS., Petros, WP., Friedman, AH., et al.[2022]

References

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

Neural stem cell-mediated CE/CPT-11 enzyme/prodrug therapy in transgenic mouse model of intracerebellar medulloblastoma. [2021]

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

Optimization of a Neural Stem-Cell-Mediated Carboxylesterase/Irinotecan Gene Therapy for Metastatic Neuroblastoma. [2020]

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

Neural stem cell-mediated delivery of irinotecan-activating carboxylesterases to glioma: implications for clinical use. [2023]

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

Irinotecan therapy in adults with recurrent or progressive malignant glioma. [2022]

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

Tumor-specific gene therapy for pancreatic cancer using human neural stem cells encoding carboxylesterase. [2018]