Phase 3 N=413 Treatment

Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor

Brain and Central Nervous System Tumors

Bottom Line

View on ClinicalTrials.gov: NCT00085202 ↗

Enrolled (actual)

413

Serious AEs

8.2%

Results posted

Feb 2014

Primary outcome: Primary: Progression-Free Survival (PFS) in ERBB2-Negative Tumors Compared to ERBB2-Positive Tumors — 79.2; 83.3; 69.6; 86.7 probability of PFS at 2 years — p=0.8001

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: filgrastim (Biological); cisplatin (Drug); cyclophosphamide (Drug); vincristine (Drug); autologous hematopoietic stem cell transplantation (Procedure); radiation therapy (Radiation)
Age: Pediatric, Adult · 3+ yrs
Sex: All
Sponsor: St. Jude Children's Research Hospital
Primary completion: Dec 2016

Outcome Measures

Outcome	Result	p-value
PRIMARY Progression-Free Survival (PFS) in ERBB2-Negative Tumors Compared to ERBB2-Positive Tumors	79.2; 83.3; 69.6; 86.7; 93.5; 71.4	0.8001
PRIMARY Progression-Free Survival (PFS) Compared Between ERBB2 Assessment and Risk Group.	83.3; 69.6; 93.5; 71.4	0.0206 sig
PRIMARY Frequency of Mutations Associated With SHH and WNT Tumors	7; 0; 0; 0; 4; 0	—
SECONDARY Reading Decoding Composite Scores in the Intervention and Standard of Care Groups	104.1; 102.4; -1.51; -1.17	0.6231
SECONDARY Number of Average Risk Patients Whose Treatment Failure Included the Posterior Fossa	6	—
SECONDARY Associative Memory for Two Risk Group at Enrollment	93.61; 98.04	—
SECONDARY Associative Memory for Two Risk Group at 5 Years After Enrollment	98.73; 93.58	—
SECONDARY Processing Speed for Two Risk Group at Enrollment	83.98; 87.29	—
SECONDARY Processing Speed for Two Risk Group at 5 Years After Enrollment	84.21; 75.71	—
SECONDARY Perceptual Speed for Two Risk Group at Enrollment	82.06; 90.04	—
SECONDARY Perceptual Speed for Two Risk Group at 5 Years After Enrollment	78.68; 72.29	—

Summary

Drugs used in chemotherapy, such as vincristine, cisplatin, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. Autologous stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy or radiation therapy. It is not yet known which radiation therapy regimen combined with chemotherapy and donor stem cell transplant is more effective in treating medulloblastoma, supratentorial primitive neuroectodermal tumor, or atypical teratoid rhabdoid tumor. This phase III trial is studying two different regimens of radiation therapy when given together with chemotherapy and autologous stem cell transplant to see how well they work in treating patients with newly diagnosed medulloblastoma, supratentorial primitive neuroectodermal tumor, or atypical teratoid rhabdoid tumor. PRIMARY OBJECTIVE: * To assess the relationship between ERBB2 protein expression in tumors and progression-free survival probability for patients with medulloblastoma. * To estimate the frequency of mutations associated with SHH and WNT tumors (as defined by gene expression profiling) via targeted sequencing performed in an independent cohort of WNT and SHH tumors (also defined by gene expression profiling).

Eligibility Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed diagnosis of 1 of the following:
Medulloblastoma
Supratentorial primitive neuroectodermal tumor (PNET)
PNET variants (ependymoblastoma, pineoblastoma, CNS neuroblastoma)
Atypical teratoid rhabdoid tumor (ATRT)
Definitive surgery for CNS tumor within the past 31 days
Meets one of the following risk criteria:
Average-risk disease
Localized disease with no overt evidence of invasion beyond the posterior fossa (or supratentorial compartment for PNET or ATRT) by intraoperative observations of the neurosurgeon AND postoperative CT scan or MRI
T4 disease eligible if all of the following are true:
Gross total resection determined by intraoperative observations of the neurosurgeon AND postoperative CT scan or MRI
Residual tumor or imaging abnormality whose size is 1.5 cm^2 at the primary site after surgery

PATIENT CHARACTERISTICS:

Age

3 to 21 at diagnosis

Performance status

Lansky 30-100% ( 8 g/dL
WBC > 2,000/mm^3
Absolute neutrophil count > 500/mm^3
Platelet count > 50,000/mm^3

Hepatic

ALT 70 mL/min

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No prior chemotherapy

Endocrine therapy

Prior corticosteroid therapy allowed

Radiotherapy

No prior radiotherapy

Surgery

See Disease Characteristics

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00085202). 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.