Immunotherapy for Ependymoma

Overseen By Sharon Dibridge

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: James Felker

Must not be taking: Interferon, Growth factors

Disqualifiers: Immune disorders, Pregnancy, Outside North America, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine (HLA-A2 restricted synthetic tumor antigen) combined with an immune-boosting cream (Imiquimod) to determine its safety and ability to trigger an immune response in children with recurring ependymoma, a type of brain tumor. It targets those whose ependymoma has returned after treatment. Eligible participants must be HLA-A2 positive (a specific genetic profile) and willing to travel to Pittsburgh for treatment sessions. 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.

Do I need to stop taking my current medications to join the trial?

The trial requires that you stop certain medications at least one week before joining, including interferon, allergy shots, growth factors, interleukins, and any investigational drugs. You must also not use immunosuppressive agents within four weeks prior to the study, except for low-dose dexamethasone.

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

Research has shown that the HLA-A2 restricted tumor antigen vaccine, when combined with imiquimod (a cream that boosts the immune system), might help the body fight cancer cells. Specific safety information from earlier studies on this vaccine is not yet available, as it remains in the early testing stages. Scientists are primarily assessing its safety for human use.

Imiquimod, however, has a well-established safety record. It is already approved for other uses, such as treating certain skin conditions, and most people tolerate it well. Some may experience mild skin reactions at the application site, but serious side effects are rare.

In summary, while the vaccine's safety is still under study, imiquimod is generally considered safe for many people. However, like any treatment, some side effects might occur, and these are usually mild. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the new immunotherapy treatment for ependymoma because it targets the cancer in a novel way. Unlike standard treatments like surgery, radiation, and chemotherapy, this approach uses a synthetic tumor antigen vaccine tailored to the patient's immune system. The vaccine, combined with imiquimod, aims to boost the body's natural defenses to recognize and attack the tumor cells specifically. This targeted action offers the potential for more effective treatment with fewer side effects, which is a significant improvement over existing therapies.

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

Research has shown that specific vaccines, such as the HLA-A2 restricted tumor antigen vaccine, combined with the medicine imiquimod, can help combat recurring ependymomas, a type of brain tumor. In one study, 55% of patients survived for at least 12 months, offering hope for those with this tumor. Another study found that patients with less aggressive tumors (WHO grade 2) experienced about 45 weeks without disease progression. These treatments enhance the body's immune system to more effectively attack tumor cells. The combination of the vaccine and imiquimod, which participants in this trial will receive, shows promise for improving outcomes in children with recurring ependymomas. ^{1 2 6 7 8}

Who Is on the Research Team?

James Felker, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for children with recurrent ependymoma, a type of brain tumor. Participants must be between 1 and 21 years old, HLA-A2 positive, have had prior standard therapy including surgery and radiation if appropriate, and be off high-dose steroids. They should not have immune deficiencies or be on immunosuppressive drugs.

Inclusion Criteria

I have been stable and on low-dose or no corticosteroids for at least a week.

I am mostly active and can care for myself.

My diagnosis is ependymoma, regardless of its grade.

Exclusion Criteria

I have received a tetanus vaccine recently or will receive it during my treatment.

I haven't taken any medications or treatments for at least a week.

I have previously received immunotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HLA-A2 restricted tumor antigen peptide vaccine in conjunction with imiquimod

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HLA-A2 restricted synthetic tumor antigen
• Imiquimod

Trial Overview

The study tests whether a vaccine made from specific tumor proteins combined with an immune-boosting cream (Imiquimod) can provoke an immune response safely in these patients. The treatment involves regular visits to Pittsburgh for vaccination over several months.

How Is the Trial Designed?

Group I: HLA-A2 restricted tumor antigen vaccine Experimental Treatment 6 Interventions

This is a single-arm study of a HLA-A2 restricted tumor antigen peptide vaccine, administered in conjunction with imiquimod

Who Is Running the Clinical Trial?

James Felker

Lead Sponsor

Trials

3

Recruited

110+

Ian F. Pollack, M.D.

Lead Sponsor

Trials

5

Recruited

130+

Solving Kids' Cancer

Collaborator

Trials

11

Recruited

200+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A study of 159 patients with grade II/III gliomas revealed significant over-expression of specific tumor-associated antigens (BCAN, CSPG4, IGF2BP3, PTPRZ1, and TNC) at both mRNA and protein levels, indicating their potential as targets for immunotherapy.

In a smaller group of 27 patients, spontaneous T cell responses to the IMA950 antigens were detected in all grade II patients and 71% of grade III patients, suggesting that these antigens are relevant for effective tumor targeting and could enhance the efficacy of immunotherapy when combined with other peptides.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antigenic expression and spontaneous immune responses support the use of a selected peptide set from the IMA950 glioblastoma vaccine for immunotherapy of grade II and III glioma. Dutoit, V., Migliorini, D., Ranzanici, G., et al.[2021]

In a study of 178 ependymoma cases, higher levels of CD3+ and CD8+ immune cells were linked to longer progression-free survival (PFS), while higher levels of FOXP3+ and CD68+ cells were associated with shorter PFS, indicating that the immune microenvironment plays a crucial role in patient outcomes.

The presence of PD-L1 was noted in a small subset of supratentorial ependymomas, suggesting potential for immunotherapy, although PD-L1 expression did not show significant prognostic value in this study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-infiltrating immune cell subpopulations and programmed death ligand 1 (PD-L1) expression associated with clinicopathological and prognostic parameters in ependymoma. Nam, SJ., Kim, YH., Park, JE., et al.[2019]

Patients with supratentorial extraventricular ependymoma (SEE) who underwent gross total resection (GTR) had significantly better progression-free survival compared to those who had subtotal resection (STR), with STR patients facing much higher recurrence risks over time.

The expression of PD-L1 was identified as an independent predictor of worse outcomes in SEE patients, suggesting that PD-L1 positivity correlates with increased recurrence rates and could serve as a reliable biological marker for prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of clinical factors and immunocheckpoint molecules in the prognosis of patients with supratentorial extraventricular ependymoma: a single-center retrospective study. Wang, L., Han, S., Yan, C., et al.[2021]

In pediatric ependymoma (EPN), particularly the supratentorial RELA fusion (ST-RELA) subtype, there is a significant expression of PD-L1, which is associated with immune evasion and T-cell exhaustion, indicating a potential target for immunotherapy.

The study suggests that clinical trials using checkpoint inhibitors targeting PD-L1/PD-1 should focus on ST-RELA tumors, as they show high levels of PD-L1 and exhausted T cells, which could benefit from these novel therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specific expression of PD-L1 in RELA-fusion supratentorial ependymoma: Implications for PD-1-targeted therapy. Witt, DA., Donson, AM., Amani, V., et al.[2019]

Ipilimumab, a monoclonal antibody used to treat melanoma, enhances T-cell activation and has been linked to improved overall survival, but it can also cause immune-related adverse events like skin rash, diarrhea, and colitis.

This report highlights a rare case of a patient developing both uveitis and hypophysitis after ipilimumab treatment, demonstrating that these immune-related side effects can occur weeks after the last dose and may present diagnostic challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab-induced hypophysitis and uveitis in a patient with metastatic melanoma and a history of ipilimumab-induced skin rash. Nallapaneni, NN., Mourya, R., Bhatt, VR., et al.[2022]

In a Phase II study involving 18 patients with leptomeningeal disease, the combination of ipilimumab and nivolumab showed promising efficacy, with 44% of patients alive at three months, surpassing the expected 18%.

The treatment had an acceptable safety profile, although one-third of patients experienced significant adverse events, including two cases leading to treatment discontinuation due to hepatitis and colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis. Brastianos, PK., Strickland, MR., Lee, EQ., et al.[2021]

In a study of 51 patients with metastatic melanoma treated with immune checkpoint inhibitors, 11.7% developed hypophysitis, highlighting a notable incidence of this immune-mediated adverse event.

Patients who experienced immune-mediated adverse events (IMAEs) showed significantly improved overall survival and progression-free survival compared to those who did not, suggesting a potential link between IMAEs and better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypophysitis induced by immune checkpoint inhibitors in a Scottish melanoma population. Wei, KZ., Baxter, M., Casasola, R.[2022]

Ipilimumab significantly improves survival rates in patients with malignant melanoma by stimulating the immune system.

While ipilimumab is generally safe, it can cause serious side effects like hypophysitis and severe diarrhea, which require prompt diagnosis and treatment to prevent fatal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lymphocytic hypophysitis due to ipilimumap therapy]. Thomsen, HH.[2017]

Immunotherapy-induced hypophysitis (IIH) occurs more frequently in males and leads to more severe pituitary dysfunction compared to primary hypophysitis (PH), with central hypocortisolism being a common feature in IIH.

Patients with IIH often present with similar symptoms to those with PH, but diabetes insipidus is very rare in IIH, and 20% of IIH patients report no symptoms at all, indicating a need for careful monitoring in patients receiving immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences between immunotherapy-induced and primary hypophysitis-a multicenter retrospective study. Amereller, F., Deutschbein, T., Joshi, M., et al.[2022]

Complete surgical resection of ependymomas is the only consistent factor that improves survival rates in pediatric patients, highlighting the importance of effective surgical intervention.

Recent genomic studies have identified unique molecular characteristics of ependymomas, suggesting that targeted therapies and personalized treatment approaches could enhance outcomes for patients with these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Management of Pediatric Ependymomas. Lin, FY., Chintagumpala, M.[2018]

Chimeric antigen receptor T cells targeting EPHA2, HER2, and interleukin 13 receptor α2 have been validated as effective treatments for recurrent medulloblastoma and ependymoma in mouse models, showing promise for bypassing the blood-brain barrier through intrathecal delivery.

The combination of these targeted T cells with azacytidine demonstrated high efficacy against multiple metastatic models of group 3 medulloblastoma and PFA ependymoma, suggesting a strong rationale for future clinical trials in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma. Donovan, LK., Delaidelli, A., Joseph, SK., et al.[2022]

In a study of 19 pediatric and 13 adult ependymomas, a high percentage of pediatric cases (95% for EphA2 and Survivin, 84% for IL-13Rα2) showed overexpression of tumor-associated antigens, indicating potential targets for immunotherapy.

The consistent expression of these antigens in both pediatric and adult ependymomas supports the feasibility of using a peptide-based vaccine targeting these antigens in clinical trials to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased expression of tumor-associated antigens in pediatric and adult ependymomas: implication for vaccine therapy. Yeung, JT., Hamilton, RL., Okada, H., et al.[2021]

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Vaccines made from HLA-A2 restricted tumor antigen peptides and imiquimod may help the body build an effective immune response to kill tumor cells. Eligibility ...

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Immunotherapy for Ependymoma

The purpose of this study is to see if vaccination with HLA-A2 restricted peptides, combined with the immunoadjuvant imiquimod is safe and can induce immune ...