High-Dose Consolidation Chemotherapy for Medulloblastoma

Recruiting at 66 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

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a prospective randomized clinical trial, to determine whether dose-intensive tandem Consolidation, in a randomized comparison with single cycle Consolidation, provides an event-free survival (EFS) and overall survival (OS). The study population will be high-risk patients (non-Wnt and non-Shh sub-groups) with medulloblastoma, and for all patients with central nervous system (CNS) embryonal tumors completing "Head Start 4" Induction. This study will further determine whether the additional labor intensity (duration of hospitalizations and short-term and long-term morbidities) associated with the tandem treatment is justified by the improvement in outcome. It is expected that the tandem (3 cycles) Consolidation regimen will produce a superior outcome compared to the single cycle Consolidation, given the substantially higher dose intensity of the tandem regimen, without significant addition of either short-term or long-term morbidities.

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.

Is high-dose consolidation chemotherapy for medulloblastoma generally safe in humans?

The treatment has been studied in children with medulloblastoma, and while it can improve survival rates, it may lead to long-term side effects, especially when combined with radiation therapy. Proton therapy, a type of radiation, might reduce some of these side effects, but more research is needed to confirm this. ^{1 2 3 4 5}

How is the High-Dose Consolidation Chemotherapy treatment for medulloblastoma different from other treatments?

This treatment is unique because it involves high-dose chemotherapy followed by stem cell rescue, which helps the body recover from the intense treatment. It is specifically designed for high-risk medulloblastoma patients and aims to improve outcomes by using a more aggressive approach compared to standard treatments. ^{2 6 7 8 9}

What data supports the effectiveness of this treatment for medulloblastoma?

Research shows that high-dose chemotherapy, often combined with stem cell support, has been effective in improving survival rates for children with high-risk medulloblastoma. This approach helps reduce the harmful effects of radiation therapy, especially in young children, and has been part of a multi-step treatment plan that has significantly increased 5-year survival rates over the years. ^{1 2 6 8 10}

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

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.

I have been diagnosed with medulloblastoma.

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

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]

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]

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]

Citations

1. Greece pubmed.ncbi.nlm.nih.gov

Chemotherapy dose-intensity and survival for childhood medulloblastoma. [2015]

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

Tandem high-dose chemotherapy and autologous stem cell rescue in children with newly diagnosed high-risk medulloblastoma or supratentorial primitive neuro-ectodermic tumors. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

High-Dose Chemotherapy in Children with Newly Diagnosed Medulloblastoma. [2022]

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

Feasibility and response to induction chemotherapy intensified with high-dose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma. [2015]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Treatment of Children and Adolescents With Metastatic Medulloblastoma and Prognostic Relevance of Clinical and Biologic Parameters. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Toxicity and Clinical Results after Proton Therapy for Pediatric Medulloblastoma: A Multi-Centric Retrospective Study. [2023]

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

A pilot study of preirradiation chemotherapy and 1800 cGy craniospinal irradiation in young children with medulloblastoma. [2006]

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

Feasibility of four consecutive high-dose chemotherapy cycles with stem-cell rescue for patients with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumor after craniospinal radiotherapy: results of a collaborative study. [2017]

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

Medulloblastoma. [2021]