Individualized Treatment for Medulloblastoma

(PNOC027 Trial)

Recruiting at 6 trial locations

Overseen By PNOC Operation Office

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must not be taking: Anti-cancer therapy

Disqualifiers: Active infection, Pregnant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

74 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop all current medications, but you must have stopped any anti-cancer treatments and recovered from their effects before joining. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the Specialized Tumor Board Treatment Plan for medulloblastoma?

The effectiveness of the Specialized Tumor Board Treatment Plan for medulloblastoma is supported by the importance of interdisciplinary collaboration in diagnosis and treatment, as well as the use of risk-adapted strategies based on clinical, radiological, and molecular data, which have been shown to improve outcomes and reduce long-term side effects in similar treatment approaches. ^{1 2 3 4 5}

What safety data exists for the individualized treatment for medulloblastoma?

The treatment for medulloblastoma, including the use of smoothened (SMO) inhibitors like sonidegib, is being studied to reduce radiotherapy-related side effects and improve safety. Long-term follow-up in trials is monitoring side effects, quality of life, and other health outcomes to ensure safety in humans. ^{2 6 7 8 9}

How does the Specialized Tumor Board Treatment Plan differ from other treatments for medulloblastoma?

The Specialized Tumor Board Treatment Plan is unique because it involves a personalized approach, tailoring treatment strategies based on the specific characteristics of each patient's tumor, such as molecular subgrouping and genetic features. This individualized plan aims to improve outcomes by integrating precision medicine and advanced therapeutic strategies, unlike standard treatments that may not consider these detailed tumor-specific factors. ^{2 4 10 11 12}

What is the purpose of this trial?

The current study will use a new treatment approach based on the molecular characteristics of each participant's tumor. The study will test the feasibility in the pilot phase of performing real-time drug screening on tissue taken during surgery in patients with relapsed medulloblastoma or ependymoma and of having a specialized tumor board assign a treatment plan based on the results of this screening and genomic sequencing. The aim of this trial is to allow every child and young adult with relapsed medulloblastoma and ependymoma to receive the most effective and least toxic therapies currently available and will pave the way for improved understanding and treatment of these tumors in the future. Moreover, if successful, it could serve as a paradigm for personalized medicine programs for other types of cancer.

Research Team

Sabine Mueller, MD, PhD, MAS

Principal Investigator

University of California, San Francisco

Lindsay Kilburn, MD

Principal Investigator

Children's National Research Institute

Robert Wechsler-Reya, PhD

Principal Investigator

Columbia University

Margaret Shatara, MD

Principal Investigator

Washington University School of Medicine

Megan Paul, MD

Principal Investigator

Rady Children's Hospital

Eligibility Criteria

This trial is for children and young adults aged 12 months to 39 years with recurrent medulloblastoma, a type of brain tumor. They must have tumors that can be surgically removed, be recovering from previous treatments, and have a certain level of physical ability. Pregnant or breastfeeding women are excluded, as well as those with other cancers or serious illnesses.

Inclusion Criteria

I have recovered from side effects of my last biological treatment, which was over a week ago.

My disease can be operated on.

I have recovered from side effects of my previous cancer treatments.

Exclusion Criteria

I finished my last treatment with a targeted drug or biologic at least 7 days ago.

Participants who are receiving any other investigational agents

I haven't had chemotherapy or radiotherapy in the last 3 weeks, or 6 weeks for specific drugs, and have recovered from any side effects.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an individualized treatment recommendation including up to four FDA-approved drugs based on real-time drug screening and genomic sequencing

Up to 2 years

Regular visits as per treatment protocol

Follow-up

Participants are monitored for safety, effectiveness, and progression after treatment

Up to 5 years

Treatment Details

Interventions

• Specialized Tumor Board Treatment Plan

Trial Overview The study tests an individualized treatment plan based on the molecular profile of each patient's tumor. It involves real-time drug screening and genomic sequencing to assign targeted therapies aimed at being effective yet less toxic.

Participant Groups

Group I: Individualized Treatment Recommendation (Pilot Phase) Experimental Treatment 2 Interventions

Participants will receive an individualized treatment recommendation including a combination of up to four FDA-approved drugs within 21 business days of tissue acquisition using the results of real-time high-throughput drug screening, whole exome sequencing (WES), and RNA sequencing.

Group II: Individualized Treatment Recommendation (Efficacy Phase) Experimental Treatment 2 Interventions

Participants will receive an individualized treatment recommendation including a combination of up to four FDA-approved drugs within 21 business days of tissue acquisition using the results of real-time high-throughput drug screening, whole exome sequencing (WES), and RNA sequencing.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Pediatric Neuro-Oncology Consortium

Collaborator

Pediatric Neuro-Oncology Consortium

Collaborator

Trials

4

Recruited

130+

Ashion Analytics

Collaborator

Trials

1

Recruited

10+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

St. Baldrick's Foundation

Collaborator

Trials

19

Recruited

9,100+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

Pacific Pediatric Neuro-Oncology Consortium

Collaborator

Trials

16

Recruited

840+

Findings from Research

In a study of 69 medulloblastoma patients, overall survival rates were 77.7% for children and 61% for adults, indicating that age and treatment timing significantly influence outcomes.

Patients with high-risk tumors had a much higher recurrence rate (41%) compared to those with standard risk (13%), highlighting the importance of risk stratification in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic outcomes of medulloblastoma in Casablanca from 2000 to 2012]. Elbachiri, M., Dao, A., Jabir, H., et al.[2015]

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]

Medulloblastomas are the most common malignant brain tumors in children, and their treatment requires a multidisciplinary approach due to their rarity and complexity.

Recent advancements in molecular understanding have led to risk-adapted treatment strategies that improve outcomes for high-risk patients while reducing long-term side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evolution of the management of pediatric and adult medulloblastoma]. Vigneron, C., Entz-Werlé, N., Lutz, P., et al.[2022]

A modified chemotherapy regimen for young children with medulloblastoma, which reduced the number of intrathecal methotrexate doses and eliminated the need for Ommaya reservoir implantation, showed promising results with four out of five patients remaining in remission for 3 to 10 years post-treatment.

The approach demonstrated safety, as no learning difficulties were observed in the children who remained in remission, suggesting that this modified treatment could be a viable option for reducing neurocognitive deficits associated with traditional radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An intrathecal limited postoperative chemotherapy regimen for the treatment of young children with nodular/desmoplastic medulloblastoma and medulloblastoma with extensive nodularity. Naung, H., Cohen, KJ.[2022]

In a study of 338 non-metastatic medulloblastoma patients, the WNT subgroup (MBWNT) was confirmed to have a favorable prognosis, but non-MBWNT tumors showed better outcomes than previously reported in broader trials, indicating the need for tailored risk assessments.

Chromosome 17 defects were found to predict poor prognosis in certain genetic backgrounds, and specific biomarkers, including patterns of chromosome 17 imbalance and MBWNT status, are essential for improving risk stratification in standard-risk medulloblastoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarker-driven stratification of disease-risk in non-metastatic medulloblastoma: Results from the multi-center HIT-SIOP-PNET4 clinical trial. Clifford, SC., Lannering, B., Schwalbe, EC., et al.[2021]

The EORTC 1634-BTG/NOA-23 trial aims to improve treatment for post-pubertal medulloblastoma patients by comparing standard-dose versus reduced-dose craniospinal radiotherapy and adding the SMO inhibitor sonidegib to standard therapy, potentially reducing toxicity and enhancing efficacy.

This study will provide valuable long-term data on treatment side effects and quality of life, which is crucial for developing better treatment strategies for this rare brain cancer in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Randomized Trials in Adults with Medulloblastoma-The Example of EORTC 1634-BTG/NOA-23. Hau, P., Frappaz, D., Hovey, E., et al.[2021]

In a Phase II study involving 53 children with high-risk medulloblastoma, oral etoposide was found to be tolerable and effective when administered during radiotherapy, leading to a high response rate with 40.4% achieving complete response and 51.1% partial response.

The study reported promising survival rates, with 2-year progression-free survival (PFS) at 76.6% and overall survival (OS) at 80.9%, indicating that this treatment regimen could improve outcomes for children with this aggressive form of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II feasibility study of oral etoposide given concurrently with radiotherapy followed by dose intensive adjuvant chemotherapy for children with newly diagnosed high-risk medulloblastoma (protocol POG 9631): A report from the Children's Oncology Group. Esbenshade, AJ., Kocak, M., Hershon, L., et al.[2018]

In a study of 47 adult medulloblastoma patients treated under the Dutch protocol, combined chemo-radiotherapy showed potential for improved survival, with 5-year progression-free survival rates of 69% for standard-risk patients and 90% for high-risk patients, although these results were not statistically significant.

The treatment regimen was associated with considerable toxicity, leading to treatment reductions and delays, particularly due to hematological and neurotoxicity, highlighting the need for careful management of side effects in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medulloblastoma in adults: evaluation of the Dutch society for neuro-oncology treatment protocol. Bleeker, L., Kouwenhoven, MCM., de Heer, I., et al.[2023]

This study analyzed 52 childhood medulloblastoma tumor samples using RNA sequencing and DNA methylation arrays, identifying four core molecular subgroups (WNT, SHH, Group 3, and Group 4) that can help tailor risk-adapted treatments.

The research revealed potential drug targets in DNA damage response pathways and identified genetic predispositions in 50% of SHH medulloblastoma patients, highlighting the importance of personalized care in treating childhood medulloblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan. Wu, KS., Ho, DM., Jou, ST., et al.[2020]

Long-term survival rates for adults with medulloblastoma are approximately 50-60% at 5 years and 40-50% at 10 years, indicating that effective treatment strategies can lead to significant survival outcomes.

The cornerstone of treatment includes radical surgery followed by specific adjuvant radiotherapy and chemotherapy regimens, with careful timing and dosage to avoid adverse effects, particularly concerning the patients' hematopoietic reserves.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medulloblastoma in adults: clinical characteristics and treatment. Brandes, AA., Palmisano, V., Monfardini, S.[2005]

Medulloblastoma, the most common malignant brain tumor in children, presents significant challenges in long-term survival and quality of life, prompting the integration of molecular subgrouping into treatment strategies to better risk stratify patients.

Current clinical trials are exploring innovative therapies, including precision medicine, epigenetic modifications, and immune therapies, to improve outcomes for patients with relapsed medulloblastoma, reflecting a commitment to advancing treatment through collaborative research efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current studies and future directions for medulloblastoma: A review from the pacific pediatric neuro-oncology consortium (PNOC) disease working group. Cooney, T., Lindsay, H., Leary, S., et al.[2022]

Medulloblastomas (MBs) can be classified into at least four core subgroups (WNT, SHH, Group 3, and Group 4) based on genetic and molecular characteristics, which can influence treatment outcomes and prognosis.

New approaches to treatment are being explored, including low-dose craniospinal irradiation and targeted molecular therapies, which aim to improve patient outcomes while minimizing side effects by tailoring interventions to the specific molecular profile of each tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Medulloblastoma]. Kanemura, Y.[2022]

References

1. France pubmed.ncbi.nlm.nih.gov

[Therapeutic outcomes of medulloblastoma in Casablanca from 2000 to 2012]. [2015]

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

Medulloblastoma. [2021]

3. France pubmed.ncbi.nlm.nih.gov

[Evolution of the management of pediatric and adult medulloblastoma]. [2022]

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

An intrathecal limited postoperative chemotherapy regimen for the treatment of young children with nodular/desmoplastic medulloblastoma and medulloblastoma with extensive nodularity. [2022]

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

Biomarker-driven stratification of disease-risk in non-metastatic medulloblastoma: Results from the multi-center HIT-SIOP-PNET4 clinical trial. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Development of Randomized Trials in Adults with Medulloblastoma-The Example of EORTC 1634-BTG/NOA-23. [2021]

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

A Phase II feasibility study of oral etoposide given concurrently with radiotherapy followed by dose intensive adjuvant chemotherapy for children with newly diagnosed high-risk medulloblastoma (protocol POG 9631): A report from the Children's Oncology Group. [2018]

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

Medulloblastoma in adults: evaluation of the Dutch society for neuro-oncology treatment protocol. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan. [2020]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Medulloblastoma in adults: clinical characteristics and treatment. [2005]

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

Current studies and future directions for medulloblastoma: A review from the pacific pediatric neuro-oncology consortium (PNOC) disease working group. [2022]

12. Japan pubmed.ncbi.nlm.nih.gov

[Medulloblastoma]. [2022]