Chemotherapy + Targeted Radiation for Brain Tumor

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

293 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: In this study a combination of anti-cancer drugs (chemotherapy) is used to treat brain tumors in young children. Using chemotherapy gives the brain more time to develop before radiation is given. The chemotherapy in this study includes the drug methotrexate. This drug was an important part of the two clinical trials which resulted in the best survival results for children less than 3 years of age with medulloblastoma. Most patients treated on this trial will also receive radiation which is carefully targeted to the area of the tumor. This type of radiation (focal conformal or proton beam radiotherapy) may result in fewer problems with thinking and learning than radiation to the whole brain and spinal cord. PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed central nervous system tumors.

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.

What data supports the effectiveness of the treatment Focal Conformal or Proton Beam Radiotherapy combined with chemotherapy for brain tumors?

Research indicates that combining chemotherapy with radiotherapy can be effective for treating brain tumors, especially those with poor prognosis, although it may lead to severe side effects. Studies have shown that this combined approach can improve survival rates and control tumor progression in some patients. ^{1 2 3 4 5}

Is the combination of chemotherapy and targeted radiation generally safe for treating brain tumors?

The combination of chemotherapy with methotrexate and radiation can cause severe neurotoxicity (nerve damage), especially when high doses are used. However, lower doses of methotrexate are better tolerated, and combining it with radiation has shown to prolong survival in some cases, though it still carries risks of toxicity. ^{6 7 8 9 10}

How is the treatment of Chemotherapy + Targeted Radiation for Brain Tumor different from other treatments?

This treatment combines chemotherapy with targeted radiation, using advanced techniques like Focal Conformal or Proton Beam Radiotherapy, which aim to precisely target the tumor while sparing healthy tissue. The use of methotrexate, a high-dose chemotherapy drug, is notable for its ability to penetrate the blood-brain barrier, potentially enhancing the effectiveness of the treatment for brain tumors. ^{1 2 3 5 11}

Research Team

Amar Gajjar, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

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

WBC > 2,000/mm3

ANC > 500/mm3

Serum creatinine < 3 times upper limit of normal (ULN)

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

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

Improving radiotherapy for brain tumors. [2005]

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

Concurrent chemotherapy and radiotherapy in patients with brain tumors. [2005]

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

Radiation oncology in brain tumors: current approaches and clinical trials in progress. [2022]

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

Dose Escalated Radiation Therapy for Glioblastoma Multiforme: An International Systematic Review and Meta-Analysis of 22 Prospective Trials. [2021]

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

Synchronous radiochemotherapy in unfavorable brain tumors of children and young adults. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

Brain stem necrosis after preradiation high-dose methotrexate. [2019]

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

Non-AIDS primary CNS lymphoma: first example of a durable response in a primary brain tumor using enhanced chemotherapy delivery without cognitive loss and without radiotherapy. [2013]

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

Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. [2022]

9. United States 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. [2022]

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

Synergistic effect between intraneoplastic methotrexate and radiation on experimental intracerebral rat gliosarcoma. [2019]

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

Local DNA Repair Inhibition for Sustained Radiosensitization of High-Grade Gliomas. [2020]