Chemotherapy + Radiation for Medulloblastoma

Not currently recruiting at 219 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different combinations of chemotherapy and radiation therapy to determine the most effective treatment for high-risk medulloblastoma in young patients. The chemotherapy drugs—vincristine sulfate, cisplatin, cyclophosphamide, and carboplatin—aim to stop tumor growth by killing the cells or preventing them from dividing. The trial seeks patients newly diagnosed with medulloblastoma who have not yet received any treatment. Participants should have a specific tumor profile, identifiable through MRI scans, before joining the trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications, but it advises avoiding certain drugs that interact with the trial medications. Specifically, drugs that strongly affect liver enzymes (like some antifungals and seizure medications) should be avoided with vincristine, and caution is advised with other medications when taking cisplatin. It's best to discuss your current medications with the trial team.

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

Research has shown that the treatments in this trial have established safety records from past studies. Carboplatin, used with radiation therapy, often causes side effects such as low white blood cell and platelet counts, which are common with chemotherapy drugs.

Cisplatin, a standard treatment for medulloblastoma, can lead to hearing loss and kidney issues. Despite these side effects, it has been used for a long time due to its effectiveness in treating these tumors.

Cyclophosphamide may cause serious side effects, especially in children who have previously undergone radiation therapy. These effects can impact the bone marrow and other body systems.

Vincristine sulfate, another drug in the trial, is widely used for various cancers and is known for side effects like nerve damage and low blood counts.

Radiation therapy, an important part of this trial, is well-known for treating medulloblastoma and can cause side effects such as tiredness and skin changes.

These treatments are in a late-stage trial, indicating they have shown some safety in earlier studies. Discussing any concerns with a healthcare provider is important.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for medulloblastoma because they combine chemotherapy and radiation in innovative ways to enhance effectiveness. Unlike most standard treatments that utilize these therapies separately, this approach integrates carboplatin or isotretinoin with radiation and traditional chemotherapy agents like cisplatin and vincristine sulfate. This combination aims to improve the overall impact on the tumor. Additionally, the use of isotretinoin in continuation therapy is a unique feature, as it may help prevent disease recurrence and manage toxicity better than current options. Overall, this multi-faceted strategy could offer a more powerful and comprehensive attack on cancer cells, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for medulloblastoma?

This trial will evaluate different combinations of treatments for medulloblastoma. Studies have shown that adding carboplatin to radiation therapy, as in Arm B, can improve survival rates for children with high-risk group 3 medulloblastoma from 54% to 73%. Research indicates that chemotherapy with cisplatin, used in Arm A, has increased survival rates in children with medulloblastoma over the past decade. Cyclophosphamide, included in the maintenance therapy for Arm A, is commonly used for this condition, though its exact effect on brain tumors remains unclear. Vincristine, another chemotherapy drug used across the arms, has improved cure rates for medulloblastoma from 40% to 70% over time. Radiation therapy, especially using protons, effectively controls the disease and offers better long-term outcomes for brain function. Together, these treatments provide a comprehensive approach with proven benefits in treating high-risk medulloblastoma in children.16789

Who Is on the Research Team?

SE

Sarah E Leary

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for young patients with a high-risk type of brain tumor called medulloblastoma, who haven't been treated before. They should have normal liver and kidney function, no history of certain drug use that affects the liver enzyme CYP450 3A4, and acceptable blood counts. Pregnant or breastfeeding women can't join, and participants must agree to use birth control. Patients need to be able to perform daily activities at least minimally despite their illness.

Inclusion Criteria

I should be careful with certain kidney-damaging medications.
I have been newly diagnosed with medulloblastoma and have not received any treatment.
I have a specific type of brain tumor called diffusely anaplastic medulloblastoma.
See 15 more

Exclusion Criteria

My cancer has not spread to distant organs (not M4).
Enrollment of patients with supratentorial PNET discontinued

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiotherapy

Patients undergo radiation therapy and receive vincristine sulfate, with carboplatin for some arms, for 6 weeks

6 weeks
5 visits per week (in-person)

Maintenance Therapy

Patients receive cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim, repeating every 28 days for 6 courses

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

  • Carboplatin
  • Cisplatin
  • Cyclophosphamide
  • Radiation Therapy
  • Vincristine Sulfate
Trial Overview The study tests different combinations of chemotherapy drugs (vincristine sulfate, cisplatin, cyclophosphamide, carboplatin) and radiation therapy in treating medulloblastoma. It aims to find out which regimen is more effective against this brain tumor by comparing how well they stop the growth or spread of cancer cells.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Active Control
Group I: Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)Experimental Treatment8 Interventions
Group II: Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)Experimental Treatment7 Interventions
Group III: Arm B (chemoradiotherapy)Experimental Treatment10 Interventions
Group IV: Arm A (chemoradiotherapy)Active Control9 Interventions

Carboplatin is already approved in United States, European Union, Canada for the following indications:

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Approved in United States as Paraplatin for:
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Approved in European Union as Carboplatin for:
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Approved in Canada as Carboplatin for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials
467
Recruited
241,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Citations

Outcome of Children With Metastatic Medulloblastoma ...The 5-year PFS and OS for patients with M+ MB were 46% ± 10% and 48% ± 10%. A recent limited-institution trial reported more encouraging results with the use of ...
Efficacy of Carboplatin and Isotretinoin in Children With High ...The addition of carboplatin during radiotherapy improved survival from 54% to 73% only for children with high-risk group 3 medulloblastoma.
The Largest High-Risk Medulloblastoma Trial Makes ...The addition of carboplatin during radiation improved survival from 54 percent to 73 percent for children with high-risk Group 3 medulloblastoma, a 19 percent ...
Medulloblastoma in the Modern Era: Review of ...Five-year EFS outcomes for high-risk medulloblastoma patients within the range of 60–70% were demonstrated in both SJMB trials, similar to ACNS0332 and HIT2000 ...
ACNS0332Carboplatin has activity as a single agent against medulloblastoma and it has been shown to enhance radiation-induced tumor cell kill. A ...
Safety and efficacy of concurrent carboplatin during full ...To assess the safety and efficacy of concurrent carboplatin during craniospinal irradiation (CSI) in high-risk/metastatic medulloblastoma.
Adjuvant chemotherapy in average-risk adult ... - BMC CancerBy analyzing safety data, as expected, the main toxicities were neutropenia and thrombocytopenia and among all patients receiving ...
Consensus treatment recommendations from SIOP-Europe ...A recent paper has suggested that the addition of carboplatin as a radiosensitiser in Group 3 patients offers a survival advantage [56] although the numbers ...
Carboplatin during radiotherapy recommended exclusively ...The study suggested that carboplatin during standard radiotherapy should only be recommended in pediatric patients with high-risk group 3 medulloblastoma.
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