CAR T-Cell Therapy for Brain Cancer

(iCAR Trial)

Not currently recruiting at 1 trial location
JR
NM
DA
MA
Overseen ByMartha Arredondo
Age: Any Age
Sex: Any
Trial Phase: Phase 1
Sponsor: Baylor College of Medicine
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for brain cancer using altered T cells, a type of immune cell, combined with antibodies to target and destroy cancer cells. The focus is on HER2-positive brain tumors, where tumor cells have a specific protein on their surface that the treatment can target. Researchers aim to find the safest dose of these modified cells and monitor for any side effects. People with HER2-positive brain cancer that hasn't responded to other treatments might be suitable for this study. As a Phase 1 trial, this research seeks to understand 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 requires that you stop other investigational cancer treatments two weeks before the CAR T cell infusion, but you can continue taking Temozolomide up to 48 hours before the infusion. Dexamethasone is allowed up to a total dose of 2 mg per day if needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that HER2-CAR T cells effectively fight cancer cells in lab tests and animal studies. In earlier research, these specially modified cells successfully targeted and attacked tumors. Reports indicate that HER2-CAR T cells can be safely administered to patients in various ways, although results may vary.

While the FDA has not yet approved HER2-CAR T cells, clinical trials have tested them for safety. The research aims to find the highest dose patients can tolerate without serious side effects. Previous experiences with CAR T cells have demonstrated that they can cause side effects, but these are often manageable. The current study seeks to understand these effects better and find ways to reduce them.12345

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

Most treatments for brain cancer, like surgery, radiation, and chemotherapy, work by directly attacking the cancer cells or shrinking tumors. However, HER2-specific CAR T-cell therapy works differently by harnessing the body's immune system. This treatment involves modifying a patient's own T-cells to specifically target and attack cancer cells expressing the HER2 protein, which is often overexpressed in certain brain cancers. Researchers are excited because this targeted approach could offer a more precise attack on cancer cells while sparing healthy ones, potentially leading to fewer side effects and more effective outcomes.

What evidence suggests that HER2-specific T cells might be an effective treatment for brain cancer?

Research has shown that a new treatment using specially modified immune cells, called HER2-specific CAR T-cells, can effectively fight tumors in both lab tests and live studies. These modified cells are designed to find and destroy tumor cells with a marker called HER2, often found on brain tumors. In some studies, MRI scans revealed that brain tumors shrank significantly after treatment with these HER2-CAR T-cells. In this trial, participants will be assigned to either a High Risk or Standard Risk arm, where researchers will evaluate different dosing schedules of HER2-specific T cells. Although the results are promising, the treatment does not work as well on solid tumors like brain cancer as it does on blood cancers. This treatment remains experimental, and further research is needed to confirm its efficacy and safety.12467

Who Is on the Research Team?

MH

Meenakshi Hegde, MD

Principal Investigator

Baylor College of Medicine - Texas Children's Hospital

NM

Nabil M Ahmed, MD

Principal Investigator

Baylor College of Medicine - Texas Children's Hospital

SN

Shoba Navai, MD

Principal Investigator

Baylor College of Medicine - Texas Children's Hospital

Are You a Good Fit for This Trial?

This trial is for patients with brain cancer that tests positive for a protein called HER2. Participants should have recurrent or resistant tumors, be able to undergo surgery if needed, and have a moderate ability to perform daily activities (Karnofsky/Lansky score ≥60). They must understand and sign the consent form.

Inclusion Criteria

Inclusion criteria at the time of procurement.
Informed consent explained to, understood by and signed by subject/guardian. Subject/guardian given copy of informed consent
I can care for myself but may need occasional help.
See 1 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Treatment

Participants receive three injections of HER2-CAR T cells two weeks apart, with dose escalation based on safety

6 weeks
3 visits (in-person) for T-cell injections, overnight observation after each injection

Follow-up

Participants are monitored for safety and effectiveness after treatment, with blood tests and imaging studies

6 weeks
Regular visits for blood tests and imaging studies

Long-term Follow-up

Participants are monitored for long-term side effects of gene transfer up to 15 years

15 years
Every 3 months for 1 year, every 6 months for 4 years, then yearly

What Are the Treatments Tested in This Trial?

Interventions

  • HER2-specific T cells
Trial Overview The study is testing T cells engineered with an antibody called anti-HER2 attached to them, known as HER2-CAR T cells. The goal is to determine the highest safe dose of these modified T cells, their side effects, and their effectiveness against brain tumors.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: HER2-specific T cells - Standard RiskExperimental Treatment1 Intervention
Group II: HER2-specific T cells - High RiskExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials
1,044
Recruited
6,031,000+

The Methodist Hospital Research Institute

Collaborator

Trials
299
Recruited
82,500+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials
114
Recruited
2,900+

Published Research Related to This Trial

Engineered human neural stem cells (NSCs) that secrete antibodies against HER2 can effectively inhibit the growth of HER2-positive breast cancer brain metastases by targeting the PI3K-Akt signaling pathway, showing promise in laboratory settings.
Combining these anti-HER2-secreting NSCs with the tyrosine kinase inhibitor tucatinib significantly improved survival in mouse models of multiple HER2-positive brain metastases, suggesting a potential new treatment strategy for patients with this challenging condition.
Combination of tucatinib and neural stem cells secreting anti-HER2 antibody prolongs survival of mice with metastatic brain cancer.Cordero, A., Ramsey, MD., Kanojia, D., et al.[2022]
Intracranial delivery of HER2-targeting CAR-T cells was found to be well tolerated in a small group of 3 patients with central nervous system (CNS) tumors, indicating a potential safe application for this therapy.
This study suggests that targeting HER2 with CAR-T cells could be a promising approach for treating CNS tumors, although further research with larger patient groups is needed to confirm efficacy.
Locoregional Delivery of CAR-T Cells Is Feasible in Pediatric CNS Tumors.[2022]
HER2-specific T cells can be effectively generated from GBM patients, showing strong antitumor activity against both HER2-positive tumor cells and their resistant stem cell populations.
In preclinical models, these T cells not only proliferated and produced key immune signals upon encountering HER2-positive GBM cells but also led to significant tumor regression, suggesting that this immunotherapy could be a promising treatment for this aggressive brain cancer.
HER2-specific T cells target primary glioblastoma stem cells and induce regression of autologous experimental tumors.Ahmed, N., Salsman, VS., Kew, Y., et al.[2022]

Citations

HER2-targeting CAR-T cells show highly efficient anti- ...HER2-CAR-T cells showed effective anti-tumor activity both in vitro and in vivo. Furthermore, HER2-specific CAR-T cells exhibited strong ...
HER2-Specific Chimeric Antigen Receptor–Modified Virus ...Tumor Responses and Survival After HER2-CAR VST Infusion. To evaluate the antiglioblastoma activity of HER2-CAR VSTs, MRI of the brain was performed 6 weeks ...
Review CAR T cell therapy for glioblastomaAll intracranial and spinal tumors decreased in size over the treatment period, becoming unmeasurable on both MRI and positron emission ...
CAR-T cell therapy for the treatment of adult high-grade ...CAR-T cell therapy for brain tumors represents a promising and rapidly growing area of research; however, successful translation remains a ...
Safety and Efficacy of Chimeric Antigen Receptor T-Cell ...Unlike the results in hematological malignancies, CAR T-cell therapy shows limited efficacy in patients with solid tumors, and a pooled objective response rate ...
Study Details | NCT02442297 | T Cells Expressing HER2- ...The purpose of this study is to find the largest safe dose of HER2-CAR T cells, to learn what the side effects are, and to see whether this experimental ...
Research progress on HER2-specific chimeric antigen ...This HER2-CAR-T cell construct has demonstrated superior cancer growth inhibition compared to traditional CAR-T cells (35). A research group ...
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