Comparison of Neurocognitive Outcome in Two Standard Regimen for Treatment of Low-risk Medulloblastoma

NCT07291102 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: COGNITO-MB2024-517133-40-00
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 2

Brief Summary

This is a trial to compare neurocognitive outcomes in the intent-to-treat population 2.5 years after diagnosis between patients with newly diagnosed, non-metastatic, SHH-activated, TP53-wt, non-MYC amplified MF randomized to the interventional arms A ("Head Start 4") or B (HIT-SKK).

Conditions

Medulloblastoma

Outcome Measures

Primary Outcomes (1)

• Neurocognitive Outcomes using WPPSIIV

  To compare neurocognitive outcomes 2.5 years after diagnosis between patients randomized to the interventional arms A ("Head Start" 4) and B (HIT-SKK). Full-Scale Intelligence Quotient (IQ) as measured by the Wechsler Preschool and Primary Scale of Intelligence (WPPSIIV) administered to those between the ages of 2 years and 6 months to 7 years and 7 months old at 2.5 years after diagnosis (+/- 6 months).

  105 months

Secondary Outcomes (21)

• PFS

  152 months

• rtPFS

  152 months

• OS

  152 months

• Second malignancies

  152 months

• Number of patients with treatment-related adverse events as assessed by CTCAE v5.0

  152 months

Study Arms (2)

Arm A: "Head Start" 4

EXPERIMENTAL

Arm A consists of 3 to 5 Induction chemotherapy cycles and one high-dose chemotherapy cycle evaluated in the "Head Start" 4 study.

Drug: Bridging Chemotherapy; Drug: Induction Cycles A1-A3; Drug: Induction Cycles A4-5; Drug: Consolidation Cycle A6

Arm B: HIT-SKK

EXPERIMENTAL

Arm B consists of 3 to 5 cycles of chemotherapy evaluated in the HIT-SKK'92 (Rutkowski et al. 2005) and HIT-2000 (NCT00303810) clinical studies.

Drug: Bridging Chemotherapy; Drug: HIT-SKK Chemotherapy Cycles B1-3; Drug: Modified HIT-SKK Cycle B4-5

Interventions

Bridging Chemotherapy DRUG

One bridging chemotherapy cycle consists of five days of therapy using Carboplatin and etoposide

Arm A: "Head Start" 4; Arm B: HIT-SKK

Induction Cycles A4-5 DRUG

Cisplatin, etoposide, cyclophosphamide, high-dose methotrexate

Arm A: "Head Start" 4

Consolidation Cycle A6 DRUG

Carboplatin, thiotepa, etoposide

Arm A: "Head Start" 4

HIT-SKK Chemotherapy Cycles B1-3 DRUG

Cyclophosphamide, vincristine, high-dose methotrexate, carboplatin, etoposide, i.ventri. methotrexate

Arm B: HIT-SKK

Modified HIT-SKK Cycle B4-5 DRUG

Cyclophosphamide, vincristine, carboplatin, etoposide

Arm B: HIT-SKK

Induction Cycles A1-A3 DRUG

Cisplatin, vincristin, etoposide, cyclophosphamide, high-dose methotrexate

Arm A: "Head Start" 4

Eligibility Criteria

• Age: Up to 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age at diagnosis \< 5 years
• Patients with institutional suspicion or diagnosis of SHH-activated MB
• Patient and family in social circumstances that will allow neuropsychological follow-up
• Ability of parents/legal representatives to understand the patient information and to personally sign and date the informed consent to participate in screening procedures
• Patient and the parents/legal representative are able and willing to participate in the entire study (if patient is eligible)

You may not qualify if:

• Patients previously treated for any other brain tumor or any type of malignant disease
• Patients, in whom compliance with toxicity management guidelines and study procedures cannot be assured
• History of hypersensitivity to an investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of an investigational medicinal product.
• Patients/parents who do not wish to abstain from treatment with live vaccines during study participation
• Patients with a language barrier too extensive to complete neuropsychological tests based on the investigator's judgement
• Patients with severe premorbid developmental delay (based on the investigator's judgement), which will not allow WPPSI-IV assessment after 2.5 years
• Patients cannot undergo MRI
• Patients with SHH-activated MB, TP53-wt demonstrated by IHC for Gab1 or p75-NGFR, Yap1, beta-catenin, and TP53 (lack of strong and widespread nuclear p53 positivity) on central review according to WHO classification 2021.
• No clinical evidence of extra-CNS metastases
• Negative CSF cytology
• No prior therapy for MB other than surgery
• No other medical contraindications to chemotherapy:
• No uncontrolled invasive fungal infection or other severe systemic infection requiring system/parental therapy
• No other severe organ dysfunctions, which cannot be clinically controlled
• No concomitant use with yellow fever vaccine and with live virus and bacterial vaccines

Sponsors & Collaborators

• Nationwide Children's Hospital: lead
• Children's of Alabama: collaborator
• German Society of Paediatric Oncology and Hematology (GPOH gGmbH): collaborator

Study Sites (2)

Children's of Alabama

Birmingham, Alabama, 35233, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

MeSH Terms

Conditions

Medulloblastoma

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Maryam Fouladi, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

• Girish Dhall, MD

  Children's Hospital of Alabama

  STUDY CHAIR

Central Study Contacts

Kelsey Troyer, PhD

CONTACT

16147228566; kelsey.troyer@nationwidechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 18, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 1, 2034
• Study Completion (Estimated): October 1, 2038
• Last Updated: December 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (2)