Phase 3 N=549 Randomized Treatment

Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma

Medulloblastoma

Bottom Line

View on ClinicalTrials.gov: NCT00085735 ↗

Enrolled (actual)

549

Serious AEs

11.1%

Results posted

Jun 2017

Primary outcome: Primary: Event-free Survival (EFS) — 76.3; 84.9; 85.8; 85.8 probability of 3 year EFS

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Cisplatin (Drug); Craniospinal Irradiation (Radiation); Cyclophosphamide (Drug); Involved-Field Radiation Therapy (Radiation); Laboratory Biomarker Analysis (Other); Lomustine (Drug); Quality-of-Life Assessment (Other); Radiation Therapy (Radiation); Vincristine Sulfate (Drug)
Age: Pediatric, Adult · 3+ yrs
Sex: All
Sponsor: Children's Oncology Group
Primary completion: Mar 2016

Outcome Measures

Outcome	Result	p-value
PRIMARY Event-free Survival (EFS)	76.3; 84.9; 85.8; 85.8	—
PRIMARY Overall Survival (OS)	90.3; 93.3; 85.5; 90.4	—
SECONDARY Local Posterior Fossa (LPF) Failure Rate	1.4; 2.7	—
SECONDARY Non-local Posterior Fossa (NLPF) Failure Rate	6.9; 2.7	—
SECONDARY Non-posterior Fossa (NPF) Failure Rate	5.1; 6.2	—
SECONDARY Post-treatment Endocrine Function by CSI Group	5.3; 6.1	—
SECONDARY Post-treatment Grade 3+ Hearing Loss as Measured by Common Terminology Criteria for Adverse Events (CTCAE) Version (v)4	11; 11	—
SECONDARY Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 1 (4 - 15 Months Post Diagnosis).	93.8; 96.2	—
SECONDARY Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 2 (27 - 48 Months Post Diagnosis)	92.2; 90.5	—
SECONDARY Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis)	90.5; 86.4	—
SECONDARY Incidence of Grade 3+ Hearing Loss at 1-year Post Treatment as Assessed by CTCAE v4	8; 8	—
SECONDARY Incidence of Endocrine Dysfunction as Measured by Growth Hormone Stimulation Tests at the Time of Completion of Therapy by Radiotherapy (RT) Group	0.0; 50.0	—
SECONDARY Overall Survival (OS) by Molecular Subgroup Based on Methylation Arrays	76.3; 97.3; 92.0; 98.3	—
SECONDARY Progression-free Survival (PFS) by Molecular Subgroup Based on Methylation Arrays	70.6; 90.6; 90.4; 98.4	—
SECONDARY Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 1 (4-15 Months Post Diagnosis)	50.7; 51.3	—
SECONDARY Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 2 (27-48 Months Post Diagnosis)	51.4; 55.0	—
SECONDARY Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis)	54.1; 58.6	—
SECONDARY Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 1 (4-15 Months Post Diagnosis)	58	—
SECONDARY Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 2 (27-48 Months Post Diagnosis)	32	—
SECONDARY Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 3 (49 - 72 Months Post Diagnosis)	69	—

Summary

This randomized phase III trial is studying how well standard-dose radiation therapy works compared to reduced-dose radiation therapy in children 3-7 years of age AND how well standard volume boost radiation therapy works compared to smaller volume boost radiation therapy when given together with chemotherapy in treating young patients who have undergone surgery for newly diagnosed standard-risk medulloblastoma. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as vincristine, cisplatin, lomustine, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy with chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether standard-dose radiation therapy is more effective than reduced-dose radiation therapy when given together with chemotherapy after surgery in treating young patients with medulloblastoma.

Eligibility Criteria

Inclusion Criteria

Histologically confirmed medulloblastoma located in the posterior fossa
Standard-risk disease
Minimal volume, non-disseminated disease, defined by the following:
Residual tumor ≤ 1.5 cm^2 confirmed by MRI with contrast imaging within 21 days after surgery
No metastatic disease in the head, spine, or cerebrospinal fluid (CSF) confirmed by both of the following:
Enhanced MRI of the spine within 5 days before surgery OR within 28 days after surgery
Negative cytological examination of CSF after surgery, but before study enrollment
Brain stem involvement allowed
Performance status - Karnofsky 50-100% (> 16 years of age)
Performance status - Lansky 30-100% (≤ 16 years of age)
Absolute neutrophil count > 1,500/uL
Platelet count > 100,000/uL (transfusion independent)
Hemoglobin > 10 g/dL (transfusions allowed)
Bilirubin = 70 mL/min/1.73m^2 or a serum creatinine based on age/gender as follows:

Age Maximum Serum Creatine (mg/dL)

1month to = 16 years male: 1.7 female: 1.4
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No prior chemotherapy
Prior corticosteroids allowed
No prior radiotherapy

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00085735). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.