High-Dose Consolidation Chemotherapy for Medulloblastoma

Not currently recruiting at 69 trial locations

Overseen By Melinda Triplet, RN

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Parth Patel

Disqualifiers: Older than 10, AT/RT, 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 aims to determine if administering higher doses of chemotherapy over three cycles is more effective for treating certain brain tumors than a single cycle. It focuses on patients with aggressive forms of medulloblastoma and other specific brain tumors who have not yet received radiation or chemotherapy. The trial will compare intense three-cycle chemotherapy with a single-cycle treatment to assess which is more effective without causing additional side effects. Patients diagnosed with specific types of brain tumors who have not started other treatments might be suitable candidates. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, and this research seeks to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify whether you need to stop taking your current medications, but it does mention that patients should not have received any chemotherapy or radiation before joining, except for corticosteroids.

What is the safety track record for these treatments?

Previous studies on treatments for medulloblastoma, similar to those being tested, have shown promising safety records. For the Tandem 3 Cycle Intensive Chemotherapy, research indicates that while it is a strong treatment, it is generally safe. One study found that 70% of patients experienced event-free survival, meaning they did not encounter treatment-related problems over five years. However, some patients did experience significant side effects, such as hearing damage, which occurred in about 18% of cases.

The Single Cycle Intensive Chemotherapy also has a good safety record. Studies have shown that 65% of patients achieved progression-free survival, meaning their cancer did not return or worsen. While these results are encouraging, this treatment carries some risk of side effects, similar to other high-dose chemotherapy options.

Lastly, the Induction phase uses a combination of five chemotherapy drugs, along with medications to help reduce side effects like low blood counts and bladder issues. This combination has been part of standard treatment protocols, demonstrating a known safety profile.

All these treatments have undergone thorough testing to ensure maximum safety, but they do carry risks. It is important to consider these factors and discuss any concerns with healthcare providers before joining a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for medulloblastoma because they offer a more intensive approach to chemotherapy, which could potentially improve outcomes. The Tandem 3 Cycle Intensive Chemotherapy uses thiotepa and carboplatin, given in two-day cycles followed by a rest period and blood cell re-infusion, repeated three times over 12 weeks. This regimen aims to aggressively target cancer cells more rapidly than standard treatments. The Single Cycle Intensive Chemotherapy incorporates a third drug, etoposide, alongside thiotepa and carboplatin, administered over six days, which might enhance the killing of cancer cells compared to traditional regimens. Both treatments focus on high-dose consolidation, which could provide a more powerful response against the tumor than current standard care options.

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

Research has shown that high-dose chemotherapy, such as the Tandem 3 Cycle Intensive Chemotherapy, one of the treatment options in this trial, yields promising results for treating medulloblastoma. Studies indicate that about 70% of patients experience 5-year event-free survival, and 74% achieve overall survival, though more follow-up is needed. Another treatment option in this trial, the Single Cycle Intensive Chemotherapy, has demonstrated significant improvements in long-term survival rates over the years, now reaching 60-70%. This suggests that intensive chemotherapy strategies have been effective for many patients with high-risk medulloblastoma. The initial treatment, known as Induction, uses a combination of drugs and has been part of the standard approach, showing good results in patients. These treatments aim to improve survival while managing side effects. ^{1 3 4 6 7}

Who Is on the Research Team?

Jonathan Finlay, MD

Principal Investigator

Global Neuro-Oncology, Inc.

Girish Dhall, MD

Principal Investigator

Children's of Alabama at UAB

Randal Olshefski, MD

Principal Investigator

Nationwide Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children under 10 years old with high-risk medulloblastoma or other CNS embryonal tumors. They must not have had previous radiation or chemotherapy, except corticosteroids, and should have adequate organ function. Children over 10, with certain excluded diagnoses like AT/RT or ependymomas, are not eligible.

Inclusion Criteria

I have been diagnosed with medulloblastoma.

Bone Marrow Function: Peripheral absolute phagocyte count (APC) > 1000/ µL. APC = numbers of banded neutrophils + segmented neutrophils + metamyelocytes + monocytes + eosinophils Please note, if institution reports differential as a percentage, then APC = [percentage of banded neutrophils + segmented neutrophils+ metamyelocytes+monocytes+eosinophils] x total white cell count

My hemoglobin level is above 8 gm/dL, even if I needed blood transfusions.

Exclusion Criteria

My cancer is not one of the excluded types listed for the study.

I was diagnosed with my condition after turning 10 years old.

My brain tumor has been biopsied.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive Induction chemotherapy with vincristine, cisplatin, cyclophosphamide, etoposide, and high-dose methotrexate for either three or five cycles, depending on response.

9-15 weeks

Consolidation

Participants undergo randomization to either single cycle or three tandem cycles of Consolidation marrow-ablative chemotherapy with autologous hematopoietic progenitor cell rescue.

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluations of event-free survival and overall survival.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Induction
• Single Cycle Intensive Chemotherapy
• Tandem 3 Cycle Intensive Chemotherapy

Trial Overview The study tests whether a more intense chemotherapy regimen (tandem 3 cycles) improves survival without adding significant side effects compared to a single cycle of intensive chemo in young patients with specific brain tumors after completing 'Head Start 4' Induction.

How Is the Trial Designed?

Group I: Tandem 3 Cycle Intensive Chemotherapy Experimental Treatment 1 Intervention

The 2 drugs to be used in this treatment are thiotepa and carboplatin. These drugs will be given over 2 days to help kill the cancer cells. After 72 hours from getting these drugs, previously collected and frozen blood cells will be thawed and returned through the venous catheter. Day -4: Thiotepa, Carboplatin Day -3: Thiotepa, Carboplatin Day -2: Rest Day -1: Rest Day 0: Re-infusion of blood cells. Following recovery from the first cycle of this chemotherapy, about 28 days following the Day 0 reinfusion of blood cells, the same cycle will be repeated again. A total of 3 cycles of this therapy will be administered, over the course of 12 weeks.

Group II: Single Cycle Intensive Chemotherapy Experimental Treatment 1 Intervention

The three drugs to be used in this research study are thiotepa, etoposide and carboplatin. These drugs will be given over 6 days to help kill the cancer cells. After 72 hours from getting these drugs, previously collected and frozen blood cells will be thawed and returned through the venous catheter. Carboplatin is given by vein over 4 hours. Thiotepa is given by vein over 3 hours. Etoposide is given by vein over 3 hours. The schedule for these drugs is as follows: Day -8: Carboplatin Day -7: Carboplatin Day -6: Carboplatin Day -5: Thiotepa, Etoposide Day -4: Thiotepa, Etoposide Day -3: Thiotepa, Etoposide Day -2: Rest Day -1: Rest Day 0: Re-infusion of blood cells

Group III: Induction Experimental Treatment 1 Intervention

The 5 chemotherapy drugs used in the Induction part of treatment are vincristine, cisplatin, cyclophosphamide, etoposide and high-dose methotrexate. Three medications are also given to help reduce the side effects of the chemotherapy drugs. Filgrastim will be given through a vein or through a tiny needle into the tissue just under the skin to help blood counts recover after the chemotherapy. Mesna will be given through a vein with cyclophosphamide to help prevent bleeding in the bladder. Leucovorin will be given through a vein after the methotrexate to protect the body from the side effects of the methotrexate.

Who Is Running the Clinical Trial?

Parth Patel

Lead Sponsor

Trials

1

Recruited

250+

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Children's of Alabama

Collaborator

Trials

10

Recruited

3,000+

Published Research Related to This Trial

Maximal safe surgery is the first step in treating medulloblastoma, followed by thorough staging and risk stratification based on histopathological and neuroradiological assessments, which should be conducted by experienced specialists.

For young children with specific types of medulloblastoma, such as desmoplastic/nodular, radiotherapy should be avoided, while older patients may require intensified treatment strategies, including high-dose chemotherapy and radiotherapy, to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medulloblastoma. von Hoff, K., Rutkowski, S.[2021]

In a study of 123 patients aged 4 to 21 with metastatic medulloblastoma, an intensified treatment regimen resulted in a 5-year event-free survival (EFS) of 62% and overall survival (OS) of 74%, showing improved outcomes compared to previous trials.

The study highlighted the importance of biological factors, such as histological subtype and MYCC/MYCN status, in predicting survival outcomes, suggesting that these factors can help tailor treatment strategies for better patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Children and Adolescents With Metastatic Medulloblastoma and Prognostic Relevance of Clinical and Biologic Parameters. von Bueren, AO., Kortmann, RD., von Hoff, K., et al.[2018]

Medulloblastoma, the most common brain tumor in children, has seen a dramatic increase in 5-year survival rates from 3% to over 70% due to a combination of surgery, radiation, and chemotherapy, particularly in high-risk patients.

Despite improved survival, many patients experience impaired neurocognitive function and quality of life after treatment, highlighting the need for more targeted and effective chemotherapy options to reduce radiation doses and minimize side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the molecular genetics and chemotherapeutic treatment of adult and paediatric medulloblastoma. Newton, HB.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8834150/

High-Dose Chemotherapy in Children with Newly Diagnosed ... The induction phase, including 5 cycles combining Etoposide, Cyclophosphamide, Cisplatin, Vincristine, Methotrexate and Temozolomide, was ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02875314

HeadStart4: Newly Diagnosed Children (<10 ... Induction chemotherapy cycles will be reduced in number from five to three for molecularly high-risk medulloblastoma (non-Shh/non-Wnt) and CNS embryonal tumors ...

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

Effective re-induction regimen for children with recurrent ... In this study, the authors looked to see how well a new combination chemotherapy consisting of intravenous irinotecan and cyclophosphamide with ...

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

Medulloblastoma in the Modern Era: Review of ... Among average-risk patients in each of the studies, 5-year EFS was 83% and 82.3%, respectively, again demonstrating efficacy of 23.4 Gy CSI dosing, as well as ...

5. siope.eu siope.eu/media/documents/escp-medulloblastoma.pdf

Medulloblastoma Four cycles induction. Cyclophosphamide, vincristine, cisplatin, etoposide. Four cycles of maintenance course. No age- and response adjusted focal radiotherapy ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02875314

NCT02875314 | HeadStart4: Newly Diagnosed Children ... Induction chemotherapy cycles will be reduced in number from five to three for molecularly high-risk medulloblastoma (non-Shh/non-Wnt) and CNS embryonal tumors ...

7. link.springer.com link.springer.com/article/10.1007/s40272-025-00726-1

Medulloblastoma: Current Standard of Care and Future ... The addition of cisplatin to CCNU and vincristine and standard radiation therapy with 36 Gy CSI led to improved cure rates and proved that ...