Reduced Radiation + Chemotherapy for Medulloblastoma

Not currently recruiting at 216 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Oncology Group

Disqualifiers: Metastatic disease, Prior radiation, Pregnancy, 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: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether lower doses of radiation combined with chemotherapy can effectively treat WNT-driven medulloblastoma, a specific type of brain tumor. The goal is to kill cancer cells while minimizing long-term side effects such as learning difficulties or hormonal issues. Participants must have a recent diagnosis of WNT-driven medulloblastoma, confirmed by specific tests, and must not have cancer that has spread to other areas. The study targets patients who have not previously undergone cancer treatments like radiation or chemotherapy. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that patients with seizure disorders can participate if their condition is well controlled with anticonvulsants. It's best to discuss your specific medications with the trial team.

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

Research shows that the chemotherapy drugs used in this trial, including cisplatin, cyclophosphamide, lomustine, and vincristine, have been tested in individuals with medulloblastoma, a type of brain tumor. Cisplatin can cause side effects like hearing loss but plays a crucial role in improving survival rates for brain tumor patients. Cyclophosphamide is considered safer in certain combinations, showing no major differences in severe blood, kidney, or liver issues compared to other treatments.

Vincristine, another drug in this trial, has been used effectively with manageable side effects in brain tumor treatments, according to past research. The trial also includes reduced radiation therapy, aiming to lower the risk of long-term side effects. While radiation effectively kills cancer cells, reducing its dose may help decrease potential learning and hormone-related problems later on.

The study's phase indicates existing evidence that these treatments are generally well-tolerated, but researchers continue to evaluate their safety and effectiveness for this specific use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment approach for medulloblastoma because it combines reduced radiation with specific chemotherapy drugs like cisplatin, cyclophosphamide, lomustine, and vincristine. Unlike the traditional approach, which often involves higher doses of radiation, this treatment uses a lower radiation dose, potentially leading to fewer side effects while still targeting the cancer effectively. Additionally, the structured timing of chemotherapy agents aims to maximize their impact and reduce toxicity, enabling a more tailored and patient-friendly treatment plan. This approach could offer a promising balance between effective cancer control and improved quality of life for patients.

What evidence suggests that reduced radiation and chemotherapy could be effective for medulloblastoma?

Research has shown that traditional treatments like chemotherapy and radiation effectively treat WNT-driven medulloblastoma, a type of brain tumor. In this trial, participants will receive a combination of vincristine and cisplatin with reduced radiation therapy, which studies have found can improve survival rates. For example, some studies associate vincristine with a 71% chance of being free from cancer progression for five years. Additionally, chemotherapy with drugs like cyclophosphamide, also part of this trial, has proven more protective than radiation alone. Combining these treatments with lower doses of radiation aims to destroy tumor cells while possibly reducing side effects. This method targets the cancer effectively while trying to lessen long-term harm. ^{6 7 8 9 10}

Who Is on the Research Team?

Nicholas J Gottardo

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for young patients with a newly diagnosed brain tumor called WNT-driven medulloblastoma. Eligible participants must be between 3 and 22 years old, have good kidney and liver function, adequate blood counts, no prior tumor-directed therapy except surgery/corticosteroids, not pregnant or breastfeeding, agree to use contraception if applicable, and able to perform required language skills for assessments.

Inclusion Criteria

I am between 6 and 10 years old with a creatinine level of 1 mg/dL or less.

My medulloblastoma is WNT type, confirmed by specific tests.

All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria

Pregnancy and Breast Feeding

Lactating females are not eligible unless they have agreed not to breastfeed their infants

I am a woman able to have children and have a negative pregnancy test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Patients undergo craniospinal radiation therapy 5 days a week for 6 weeks

6 weeks

5 visits per week (in-person)

Maintenance Therapy (Weeks 1, 3, 5, and 7)

Patients receive lomustine orally on day 1, vincristine sulfate intravenously on days 1, 8, and 15, and cisplatin intravenously on day 1. Treatment repeats every 42 days.

6 weeks per cycle

Maintenance Therapy (Weeks 2, 4, and 6)

Patients receive cyclophosphamide and mesna intravenously on days 1 and 2, and vincristine sulfate intravenously on days 1 and 8. Treatment repeats every 28 days.

4 weeks per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Every 3 months for 2 years, every 6 months for 2 years, then annually for 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Cyclophosphamide
• Lomustine
• Radiation Therapy
• Vincristine

Trial Overview The study tests whether lower doses of radiation therapy to the brain/spine along with chemotherapy (cisplatin, vincristine sulfate, cyclophosphamide and lomustine) are effective in treating WNT-driven medulloblastoma while reducing late side effects like learning difficulties or hormone deficiencies.

How Is the Trial Designed?

Group I: Treatment (reduced radiation therapy and chemotherapy) Experimental Treatment 8 Interventions

RADIATION THERAPY: Beginning 4-5 weeks after surgery, patients undergo craniospinal radiation therapy 5 days a week for 6 weeks. MAINTENANCE THERAPY (WEEKS 1, 3, 5, and 7): Beginning 4-6 weeks after completion of radiation therapy patients receive lomustine PO on day 1, vincristine sulfate IV over 1 minute or via minibag on days 1, 8, and 15, and cisplatin IV over 6 hours on day 1. Treatment repeats every 42 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY (WEEKS 2, 4, AND 6): Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 2, mesna IV over 15-30 minutes on days 1 and 2, and vincristine sulfate IV over 1 minute or via minibag on days 1 and 8. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the trial.

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

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+

Published Research Related to This Trial

In a study of 23 children with high-risk medulloblastoma, replacing cisplatinum with carboplatin in the chemotherapy protocol resulted in a 5-year overall survival rate of 60% and a 5-year progression-free survival rate of 41.8%.

The revised protocol showed a significant reduction in ototoxicity, with 11 out of 12 patients tested having normal hearing (grade 0) after treatment, indicating a safer option for managing this common complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of newly diagnosed high risk medulloblastoma treated with carboplatin, vincristine, cyclophosphamide and etoposide. Sirachainan, N., Pakakasama, S., Anurathapan, U., et al.[2018]

In a study of 26 pediatric patients with high-risk medulloblastoma, a treatment regimen of carboplatin, etoposide, and radiotherapy resulted in a 69% global survival rate and a 64% disease-free survival rate after 60 months.

The treatment was found to be safe, with no significant renal or auditory toxicity, and any hematological toxicity experienced was temporary and reversible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival of patients with medulloblastoma treated with carboplatin and etoposide before and after radiotherapy. Lopez-Aguilar, E., Sepulveda-Vildosola, AC., Rivera-Marquez, H., et al.[2018]

In a study of 17 children with high-risk medulloblastoma, the treatment combining weekly vincristine during radiation and adjuvant carboplatin and vincristine resulted in a 3-year overall survival rate of 70.6% and a progression-free survival (PFS) rate of 58.8%.

The treatment was generally well tolerated, with only 17.6% of patients experiencing severe neutropenia during radiation, although complications increased during adjuvant chemotherapy, indicating that while the approach is effective, patients with metastatic disease may need more aggressive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant weekly vincristine and radiation followed by adjuvant vincristine and carboplatin in the treatment of high risk medulloblastoma: Ain Shams University Hospital and Sohag Cancer Center study. Salama, MM., Ghorab, EM., Al-Abyad, AG., et al.[2020]

In a study of 24 medulloblastoma patients treated with carboplatin instead of cisplatin, 23 patients were alive at the time of assessment, indicating a favorable overall survival rate.

Only 10.5% of patients experienced significant hearing loss, suggesting that carboplatin has a lower risk of ototoxicity compared to traditional cisplatin treatments, especially in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and ototoxicity: hearing loss rates among survivors of childhood medulloblastoma. Musial-Bright, L., Fengler, R., Henze, G., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7413074/

CNS penetration of cyclophosphamide and metabolites in ... Cyclophosphamide is widely used to treat children with medulloblastoma; however, little is known about its brain penetration.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2666251/

Efficacy of high-dose chemotherapy or standard salvage ... Clinical characteristics, treatment, and outcome in 12 patients with recurrent medulloblastoma treated with high-dose chemotherapy (group B). Age at Diagnosis ( ...

3. academic.oup.com academic.oup.com/noa/article/6/1/vdae070/7668106

Effective re-induction regimen for children with recurrent ... There is no standard treatment for the recurrence of medulloblastoma, the most common malignant childhood brain tumor, and prognosis remains dismal.

4. ar.iiarjournals.org ar.iiarjournals.org/content/32/9/3885

Chemotherapy Dose-intensity and Survival for Childhood ... A protective effect for chemotherapy versus craniospinal radiotherapy alone (5-year OS of 58.2% versus 51.6%) was found. Individually, vincristine, cisplatin, ...

5. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2811045

Sustained Survival Benefit in Recurrent Medulloblastoma ... Although this treatment is highly effective for most patients, approximately 30% of patients will experience relapse of their disease, often ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4591537/

Cumulative Cisplatin Dose Is Not Associated With Event-Free ... Survival rates for children with medulloblastoma have risen over the past decade, in part due to the addition of cisplatin-containing adjuvant chemotherapy.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23956184/

Cumulative cisplatin dose is not associated with event-free or ... Results: Eight-year event-free survival (EFS) and overall survival (OS) estimates were 78.2 ± 2.6% and 83.9 ± 2.4%, respectively. Only 73 patients received the ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1878747923001307

Medulloblastoma in the Modern Era: Review of ... Outcomes remain inferior for patients with high-risk disease (60–70% 5-year EFS and OS), motivating investigation of treatment intensification strategies [5, 6, ...

9. link.springer.com link.springer.com/article/10.1007/s11060-025-05098-7

Impact of partial substitution of cisplatin with ... Partial substitution of cisplatin with cyclophosphamide showed a better toxicity profile, particularly for ototoxicity and neurotoxicity, with no significant ...

10. medicine.yale.edu medicine.yale.edu/ycci/clinicaltrials/trial/a-study-of-treatment-for-medulloblastoma-using-sodium-thiosulfate-to-reduce-hearing-loss/

A Phase 3 Study of Sodium Thiosulfate for Reduction of ... Cisplatin may cause hearing loss as a side effect. In the average-risk medulloblastoma patients, this trial tests whether the addition of ...