Reduced Radiation + Chemotherapy for Medulloblastoma

Recruiting at 207 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

45 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment for medulloblastoma?

Research shows that chemotherapy, including drugs like vincristine and cisplatin, is increasingly effective for treating medulloblastoma, especially when combined with radiation therapy. Studies suggest that adding chemotherapy to reduced-dose radiotherapy may improve survival rates and reduce the need for higher doses of radiation. ^{1 2 3 4 5}

Is the treatment of reduced radiation and chemotherapy for medulloblastoma generally safe in humans?

The treatment involving reduced radiation and chemotherapy for medulloblastoma has shown some safety concerns, including short-term toxicity and potential hearing loss (ototoxicity) due to radiation and certain chemotherapy drugs like cisplatin. However, substituting cisplatin with carboplatin may reduce the risk of hearing loss, although other side effects like hematologic toxicity (blood-related side effects) can still occur. ^{3 6 7 8 9}

How does the treatment of reduced radiation and chemotherapy for medulloblastoma differ from other treatments?

This treatment is unique because it combines reduced-dose radiation with chemotherapy to potentially improve survival rates while minimizing the harmful side effects of full-dose radiation, especially in children. The approach aims to balance effective cancer treatment with reducing long-term damage, which is particularly important for young patients. ^{3 4 5 10 11}

What is the purpose of this trial?

This phase II trial studies how well reduced doses of radiation therapy to the brain and spine (craniospinal) and chemotherapy work in treating patients with newly diagnosed type of brain tumor called WNT)/Wingless (WNT)-driven medulloblastoma. Recent studies using chemotherapy and radiation therapy have been shown to be effective in treating patients with WNT-driven medulloblastoma. However, there is a concern about the late side effects of treatment, such as learning difficulties, lower amounts of hormones, or other problems in performing daily activities. Radiotherapy uses high-energy radiation from x-rays to kill cancer cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, vincristine sulfate, cyclophosphamide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving reduced craniospinal radiation therapy and chemotherapy may kill tumor cells and may also reduce the late side effects of treatment.

Research Team

Nicholas J Gottardo

Principal Investigator

Children's Oncology Group

Eligibility Criteria

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.

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

My medulloblastoma is WNT type, confirmed by specific tests.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

References

1. England 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. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

Combination chemotherapy with ifosfamide, cisplatin, and etoposide for medulloblastoma: single-institute experience and differences in efficacy for subgroups of medulloblastoma. [2021]

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

Safety and efficacy of concurrent carboplatin during full-dose craniospinal irradiation for high-risk/metastatic medulloblastoma in a resource-limited setting. [2021]

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

Chemotherapy for medulloblastomas and primitive neuroectodermal tumors. [2019]

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

Medulloblastoma in young children. [2010]

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

Carboplatin and ototoxicity: hearing loss rates among survivors of childhood medulloblastoma. [2021]

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

Neurocognitive functioning and health-related quality of life in adult medulloblastoma patients: long-term outcomes of the NOA-07 study. [2021]

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

Survival of patients with medulloblastoma treated with carboplatin and etoposide before and after radiotherapy. [2018]

9. Scotland pubmed.ncbi.nlm.nih.gov

Outcome of newly diagnosed high risk medulloblastoma treated with carboplatin, vincristine, cyclophosphamide and etoposide. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Chemotherapy for children with medulloblastoma. [2023]

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

Treatment strategies for medulloblastoma and primitive neuroectodermal tumors. [2019]