Chemotherapy + Targeted Radiation for Brain Tumor

Not currently recruiting at 5 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Radiotherapy, Chemotherapy

Disqualifiers: Age, CNS metastasis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy and targeted radiation to treat brain tumors in young children. The researchers aim to determine if using these treatments together can support brain development before applying radiation, potentially reducing future learning and thinking problems. The chemotherapy includes methotrexate, which past studies have proven effective for certain brain tumors in children under three years old. Children under five with newly diagnosed specific brain tumors, such as medulloblastoma or high-grade glioma, who have only undergone surgery, may qualify for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications, but it does mention that no prior chemotherapy or radiotherapy is allowed, except for corticosteroid therapy.

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

Research has shown that chemotherapy, including methotrexate, has been part of successful treatments for young children with brain tumors like medulloblastoma. In previous studies, this drug improved survival rates among young patients.

Targeted radiation, such as proton beam therapy, is considered safer than traditional methods. It focuses directly on the tumor, reducing potential side effects, especially those affecting cognitive functions.

For high-risk patients, similar therapies have successfully prevented tumor growth. Although this information comes from various studies, it indicates that these treatments are generally well-tolerated by patients.

These treatments are currently being tested in a phase 2 trial, which follows earlier research that demonstrated some safety. This phase focuses on the treatment's effectiveness, while safety continues to be closely monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining chemotherapy with targeted radiation for brain tumors because it offers a more tailored approach to treatment. Traditional treatments often involve broad radiation, which can affect healthy brain tissue, but focal conformal and proton beam radiotherapy specifically target tumor sites, potentially reducing side effects. This precision, alongside induction chemotherapy, could improve outcomes for patients with varying risk levels of brain tumors, such as medulloblastoma and high-grade gliomas. By categorizing patients into low, intermediate, and high-risk therapy groups, the treatment aims to provide a customized plan that aligns with the severity of the disease, potentially enhancing effectiveness and safety.

What evidence suggests that this trial's treatments could be effective for brain tumors in young children?

Research has shown that chemotherapy, including methotrexate, has significantly improved survival rates in young children with brain tumors like medulloblastoma. Methotrexate played a crucial role in past studies that achieved the best survival outcomes for children under three with this condition. In this trial, children at low risk will receive induction chemotherapy followed by low-risk therapy, which includes targeted radiation, and shows promise in controlling the disease. For high-risk patients, where the cancer has spread to the central nervous system, the trial involves induction chemotherapy followed by high-risk therapy, with early findings linking these treatments to disease control. Overall, combining chemotherapy with targeted radiation offers a strategic approach to treating brain tumors while reducing long-term effects on thinking and memory. ^{6 7 8 9 10}

Who Is on the Research Team?

Amar Gajjar, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for young children with newly diagnosed brain tumors, including medulloblastoma and ependymoma. Eligible kids must have had recent surgery but no prior chemo or radiation, except steroids. They need to have certain blood cell counts within a healthy range and be under 3 years old at diagnosis (or under 5 for specific conditions).

Inclusion Criteria

I have a newly diagnosed brain tumor, such as Medulloblastoma or Glioma.

WBC > 2,000/mm3

ANC > 500/mm3

Exclusion Criteria

Living outside the US

I have had a condition where my lymphocytes multiply unusually.

I haven't had any cancer, except for skin cancer, in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive induction chemotherapy including high-dose intravenous methotrexate

Approximately 4 months

Consolidation Chemotherapy

Participants receive consolidation therapy including cyclophosphamide and pharmacokinetically targeted topotecan

Approximately 2 months

Maintenance Chemotherapy

Participants receive oral maintenance therapy

Up to 1 year

Radiation Therapy

Focal irradiation is given to intermediate risk patients who have reached at least 12 months of age upon completion of induction

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 6 months for 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Focal Conformal or Proton Beam Radiotherapy
• High-Risk Therapy
• Induction Chemotherapy
• Intermediate-Risk Therapy
• Low-Risk Therapy
• Methotrexate

Trial Overview

The study tests how well a mix of chemotherapy drugs works alongside targeted radiation therapy in treating brain tumors in kids. The goal is to delay radiation until the child's brain has developed more, potentially reducing cognitive side effects.

How Is the Trial Designed?

Group I: Low-Risk Patients Experimental Treatment 2 Interventions

Patients with GTR/M0 medulloblastoma, nodular desmoplastic or high grade glioma histology will receive induction chemotherapy and low-risk therapy. Note: Accrual to the low-risk medulloblastoma cohort is closed as of 12/2/2015. Accrual to the low-risk high grade glioma remains open.

Group II: Intermediate-Risk Therapy Experimental Treatment 2 Interventions

Patients with M0 medulloblastoma or nodular desmoplastic histology with less than a GTR, other histologic diagnoses with no metastatic disease, will receive induction chemotherapy and intermediate-risk therapy.

Group III: High-Risk Patients Experimental Treatment 2 Interventions

Patients with CNS metastatic disease will receive induction chemotherapy and high-risk therapy.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

University of Florida

Collaborator

Trials

1,428

Recruited

987,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

The Pew Charitable Trusts

Collaborator

Trials

4

Recruited

3,100+

Published Research Related to This Trial

Adding rituximab to methotrexate-based chemotherapy for primary CNS lymphoma significantly increased the complete response (CR) rate, with 44% achieving CR after five cycles and 78% after seven cycles, indicating improved treatment efficacy.

Reduced-dose whole-brain radiotherapy (23.4 Gy) after achieving CR did not lead to neurocognitive decline, suggesting it is a safe option for patients, while the most common toxicities observed were manageable, such as neutropenia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. Shah, GD., Yahalom, J., Correa, DD., et al.[2022]

Radiation therapy is crucial for treating adult brain tumors, but its application is changing based on tumor type, with ongoing trials exploring how to enhance its effectiveness and minimize side effects.

For low-grade gliomas, researchers are focusing on identifying patients who can safely delay radiation until necessary, while in cases like meningioma, advanced techniques like radiosurgery are improving outcomes for patients with a good prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation oncology in brain tumors: current approaches and clinical trials in progress. Chan, MD., Tatter, SB., Lesser, G., et al.[2022]

In a study of 17 patients aged 2 to 25 years with unfavorable brain tumors, a combined treatment of chemotherapy and radiotherapy led to a median overall survival of 36 months, with 9 patients still alive at a median follow-up of 25 months.

While the treatment showed promise with 4 complete remissions and 2 partial remissions, it also resulted in severe toxicity, including one therapy-related death, highlighting the need for careful management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synchronous radiochemotherapy in unfavorable brain tumors of children and young adults. Urban, C., Benesch, M., Pakisch, B., et al.[2019]

Radiation oncologists are exploring various innovative approaches, such as interstitial implants and stereotactic radiosurgery, to enhance cure rates for primary brain tumors while aiming to reduce long-term side effects.

These new radiation techniques must be integrated into a comprehensive treatment plan that includes other therapies to effectively manage primary malignant brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving radiotherapy for brain tumors. Woo, SY., Maor, MH.[2005]

Current treatments for brain tumors are often inadequate, leading to ongoing research into the use of concurrent chemotherapy and radiotherapy to improve patient outcomes.

Trials are exploring new agents that can effectively cross the blood-brain barrier and minimize overlapping toxicities, which may enhance the safety and efficacy of combined therapies for brain tumor patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemotherapy and radiotherapy in patients with brain tumors. Glantz, MJ., Kim, L., Choy, H., et al.[2005]

In a study of 57 patients treated with high-dose methotrexate-based chemotherapy, the overall median survival was 51 months, with particularly favorable outcomes for patients younger than 60, where 74% were alive at last follow-up.

Seventeen patients experienced treatment-related neurotoxicity, mostly among those who received whole brain radiotherapy, suggesting that for older patients, it may be safer to avoid this treatment to reduce neurotoxic risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. Gavrilovic, IT., Hormigo, A., Yahalom, J., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11719842/

Glioblastoma: Clinical Presentation, Multidisciplinary ...

Typical survival for newly diagnosed patients is 12–15 months with a two-year survival rate below 30%. Treatment generally includes surgical ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00602667

NCT00602667 | Risk-Adapted Therapy for Young Children ...

Patients with GTR/M0 medulloblastoma, nodular desmoplastic or high grade glioma histology will receive induction chemotherapy and low-risk therapy. Note: ...

3.

immunitybio.com

immunitybio.com/initial-data-shows100-disease-control-in-5-out-of-5-patients-with-recurrent-glioblastoma-with-two-patients-in-near-complete-response-treated-with-immunitybios-anktiva-nk-cell-therapy-p/

Initial Data Shows 100% Disease Control in 5 Out of 5 ...

Initial Data Shows 100% Disease Control in 5 Out of 5 Patients With Recurrent Glioblastoma With Two Patients in Near Complete Response Treated ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12109283/

Predicting Treatment Outcomes in Glioblastoma: A Risk Score ...

Stratifying patients using this model revealed a strong correlation between poor survival outcomes and more aggressive tumor characteristics, ...

5.

nature.com

nature.com/articles/s41698-024-00753-0

CAR-T cell therapy for the treatment of adult high-grade ...

GBM accounts for more than half of all malignant central nervous system (CNS) tumors, with a five-year survival rate of less than 10%. The ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3410654/

Phase I Clinical Trial Outcomes in 93 Patients with Brain ...

For the 93 patients with brain metastases, the rates of SD lasting at least 4 months and PR/CR were 15% and 2%, respectively (Table 3). In these 93 patients, ...

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.21.02314

Treatment for Brain Metastases: ASCO-SNO-ASTRO ...

There is very little evidence to support survival benefit from surgery in patients with uncontrolled systemic disease or with multiple brain metastases and to ...

8.

cns.org

cns.org/guidelines/treatment-adults-metastatic-brain-tumors/9-update-of-role-of-emerging-investigational-thera

9. Update of The Role of Emerging and Investigational ...

In patients with parenchymal brain metastases, does the use of molecular targeted agents provide benefit in terms of local control, overall survival (OS), ...

9.

sciencedirect.com

sciencedirect.com/science/article/pii/S2468294225001339

Systemic therapy breakthroughs in the management of ...

HER2+ mBC has a high brain metastasis incidence (35–50 %), with poor prognosis. •. Local treatment of active brain metastases is guided by the patient's ...

10.

nature.com

nature.com/articles/s43856-024-00445-7

Estimating the risk of brain metastasis for patients newly ...

We aimed to develop and validate models to predict risk of BM at diagnosis for the most common cancer types that spread to the brain.