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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for individuals with high-grade gliomas, an aggressive brain tumor that has returned after treatment. Researchers are testing a combination of genetically modified neural stem cells (carboxylesterase-expressing allogeneic neural stem cells) and the chemotherapy drug irinotecan to determine if this pair can increase tumor cells' sensitivity to treatment. The trial aims to identify the optimal dose and understand any side effects. It may suit those whose high-grade brain tumor has recurred despite previous treatments like radiation and temozolomide and who require further surgery or biopsy. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

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

Research has shown that a type of stem cell treatment, using specialized cells that target brain tumors, is safe. These stem cells focus on the tumor, protecting healthy brain tissue and reducing the risk of side effects in areas outside the tumor.

Studies indicate that the drug irinotecan causes fewer severe side effects in brain tumor treatments compared to other cancer drugs. Patients often experience fewer common side effects, such as diarrhea, making it easier to tolerate.

Both treatments are being tested together to assess their safety and effectiveness. As this trial is in its early stages, the main goal is to observe patient responses and determine the best dose. This phase is crucial for collecting safety information and ensuring it is safe for further testing. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for brain tumors?

Researchers are excited about this treatment for brain tumors because it combines stem cell therapy with chemotherapy in a novel way. Unlike standard treatments, which typically involve surgery, radiation, and chemotherapy, this approach uses carboxylesterase-expressing allogeneic neural stem cells that are delivered directly into the brain. These stem cells are designed to enhance the effectiveness of the chemotherapy drug irinotecan, which is given intravenously. This combination aims to target cancer cells more precisely and potentially reduce the side effects associated with traditional chemotherapy. The innovative use of neural stem cells to boost the impact of irinotecan could offer a more effective and targeted treatment for patients with brain tumors.

What evidence suggests that this treatment might be an effective treatment for brain tumors?

This trial will evaluate the combination of carboxylesterase-expressing allogeneic neural stem cells and irinotecan hydrochloride for treating brain tumors. Studies have shown that certain types of stem cells can make brain tumors more responsive to chemotherapy. Research indicates that these stem cells can locate and target aggressive tumor cells, slowing their growth. Early findings suggest that using these stem cells with irinotecan enhances its effectiveness in mice. Irinotecan has shown promise in treating recurring brain tumors, with about 15% of patients experiencing tumor shrinkage and over half maintaining stable disease. This combination treatment aims to strengthen irinotecan's impact on aggressive brain tumors known as high-grade gliomas. ^{1 4 5 6 7}

Who Is on the Research Team?

Jana L Portnow

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02192359

Carboxylesterase-Expressing Allogeneic Neural Stem ... This phase I trial studies the side effects and best dose of carboxylesterase-expressing allogeneic neural stem cells when given together with irinotecan ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10458428/

Anti-Cancer Effect of Neural Stem Cells Transfected with ... NSCs transduced with rCE and sTRAIL genes showed a significant anti-cancer effect on brain metastatic lung cancer in vivo and in vitro.

3. app.dimensions.ai app.dimensions.ai/details/grant/grant.4244078

A Phase I Study of Intracranially Administered ... Data from animal models have demonstrated the safety and efficacy of NSCs for tracking to invasive tumor cells as well as to distant micro-tumor foci and ...

4. cell.com cell.com/molecular-therapy-family/oncology/fulltext/S2372-7705(16)30053-5

Optimization of a Neural Stem-Cell-Mediated ... This resulted in significantly delayed progression of tumor growth in mice that received hCE1m6-NSCs in combination with the drug (15 mg/kg). In addition, there ...

5. researchgate.net researchgate.net/publication/258117641_Neural_Stem_Cell-Mediated_Delivery_of_Irinotecan-Activating_Carboxylesterases_to_Glioma_Implications_for_Clinical_Use

(PDF) Neural Stem Cell-Mediated Delivery of Irinotecan ... Here, we report that transduced NSCs transiently expressed high levels of active CE enzymes, retained their tumor-tropic properties, and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5693135/

STEM-32. PRE-CLINICAL SAFETY AND EFFICACY ... Human neural stem cells (NSCs) are inherently tumor-tropic, localizing to invasive brain tumor foci following intracerebral administration in preclinical ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11441620/

Cell and gene therapy in Neuro-oncology - PubMed Central Gene therapy is a promising and versatile tool in neuro-oncology because it can be locally administered during initial tumor resection and minimizes the risk ...