NCT07291102

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

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 96 (estimated)
• Sponsor: Nationwide Children's Hospital · Academic / Other
• Sex: All
• Age: 5 Years
• Healthy volunteers: Not accepted

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).

Detailed description

In this study, two highly effective irradiation-sparing treatment regimens are being compared in patients with low-risk early childhood MB: 1. Arm A: The "Head Start" 4 regimen developed by the North American Head Start Consortium. This approach uses intensive Induction chemotherapy and Consolidation with HDCT and has led to equally favorable results in this subgroup -- 3y PFS was 96% for infants and young children with M0, SHH MB; 5y EFS was 93% for M0, DMB on the predecessor "Head Start" 3 study. 2. Arm B: The HIT-SKK regimen developed within the GPOH. This regimen combines systemic chemotherapy with intraventricular MTX, leading to 93% 5-year PFS in low-risk patients. Both treatment regimens use high-dose i.v. MTX, but only the HIT-SKK regimen also uses intraventricular administration of MTX directly into the CSF in addition to i.v. MTX. Given the long-term neurocognitive deficits of MTX have been described in childhood leukemia, and the pathogenesis of MTX-induced CNS-damage has been described, this has raised some concerns. Similarly, highly intensive, HDCT containing "Head Start" chemotherapy carries specific risks for the neurocognitive outcomes. Encouragingly, five years after HIT-SKK treatment including intraventricular MTX, young children with MB have a mean fluid intelligence score of 93.8 points. The full-scale IQ after "Head Start" chemotherapy is 95.4 and likewise within normal range. On the other hand, highly intensive, HDCT/AuHCR containing "Head Start" chemotherapy carries specific risks for the neurocognitive outcomes. However, neurocognitive outcomes after the HIT-SKK and "Head Start" chemotherapy regimens are difficult to compare from existing data, because of small sample sizes and inhomogeneous assessment tools used in prior studies. Therefore, a confirmatory study utilizing the same measures administered at the same time points is required to identify clinically relevant differences. In addition, survival, occurrence of second malignancies, neurological and endocrine deficits, hearing loss, and psychosocial comorbidities are also of high relevance in survivors of MB and may differ after both regimens. Since these also severely limit the survivors' potential for activity and participation in everyday life and affect their parents and siblings as well, this information will also be recorded.

Conditions

• Medulloblastoma

Interventions

Type	Name	Description
DRUG	Bridging Chemotherapy	One bridging chemotherapy cycle consists of five days of therapy using Carboplatin and etoposide
DRUG	Induction Cycles A1-A3	Cisplatin, vincristin, etoposide, cyclophosphamide, high-dose methotrexate
DRUG	Induction Cycles A4-5	Cisplatin, etoposide, cyclophosphamide, high-dose methotrexate
DRUG	Consolidation Cycle A6	Carboplatin, thiotepa, etoposide
DRUG	HIT-SKK Chemotherapy Cycles B1-3	Cyclophosphamide, vincristine, high-dose methotrexate, carboplatin, etoposide, i.ventri. methotrexate
DRUG	Modified HIT-SKK Cycle B4-5	Cyclophosphamide, vincristine, carboplatin, etoposide

Timeline

• Start date: 2026-07-01
• Primary completion: 2034-10-01
• Completion: 2038-10-01
• First posted: 2025-12-18
• Last updated: 2025-12-18

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study