HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors

NCT02875314 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: IRB15-00399
• Study Type: interventional
• Target: 250
• Locations: 3 countries
• Sites: 62

Brief Summary

This is a prospective randomized clinical trial, to determine whether dose-intensive tandem Consolidation, in a randomized comparison with single cycle Consolidation, provides an event-free survival (EFS) and overall survival (OS). The study population will be high-risk patients (non-Wnt and non-Shh sub-groups) with medulloblastoma, and for all patients with central nervous system (CNS) embryonal tumors completing "Head Start 4" Induction. This study will further determine whether the additional labor intensity (duration of hospitalizations and short-term and long-term morbidities) associated with the tandem treatment is justified by the improvement in outcome. It is expected that the tandem (3 cycles) Consolidation regimen will produce a superior outcome compared to the single cycle Consolidation, given the substantially higher dose intensity of the tandem regimen, without significant addition of either short-term or long-term morbidities.

Conditions

Medulloblastoma; Central Nervous System Embryonal Tumors

Outcome Measures

Primary Outcomes (2)

• Compare tandem consolidation vs. single cycle consolidation A

  Dose-intensive tandem Consolidation will be compared with single cycle consolidation via randomization. The randomized consolidations will provide an event-free survival (EFS) analysis after completing "Head Start 4" Induction.

  5 years

• Compare tandem consolidation vs. single cycle consolidation B

  Dose-intensive tandem Consolidation will be compared with single cycle consolidation via randomization. The randomized consolidations will provide an overall survival (OS) analysis after completing "Head Start 4" Induction.

  5 years

Secondary Outcomes (9)

• Induction Cycle Reduction

  5 years

• Uniform Treatment Regimen

  5 years

• Therapy-Related Hearing Loss Evaluation A

  5 years

• Therapy-Related Hearing Loss Evaluation B

  5 years

• Neuropsychological effects will be evaluated using age based tests and questionnaires.

  5 years

Study Arms (3)

Induction

EXPERIMENTAL

The 5 chemotherapy drugs used in the Induction part of treatment are vincristine, cisplatin, cyclophosphamide, etoposide and high-dose methotrexate. Three medications are also given to help reduce the side effects of the chemotherapy drugs. Filgrastim will be given through a vein or through a tiny needle into the tissue just under the skin to help blood counts recover after the chemotherapy. Mesna will be given through a vein with cyclophosphamide to help prevent bleeding in the bladder. Leucovorin will be given through a vein after the methotrexate to protect the body from the side effects of the methotrexate.

Drug: Induction

Single Cycle Intensive Chemotherapy

EXPERIMENTAL

The three drugs to be used in this research study are thiotepa, etoposide and carboplatin. These drugs will be given over 6 days to help kill the cancer cells. After 72 hours from getting these drugs, previously collected and frozen blood cells will be thawed and returned through the venous catheter. Carboplatin is given by vein over 4 hours. Thiotepa is given by vein over 3 hours. Etoposide is given by vein over 3 hours. The schedule for these drugs is as follows: Day -8: Carboplatin Day -7: Carboplatin Day -6: Carboplatin Day -5: Thiotepa, Etoposide Day -4: Thiotepa, Etoposide Day -3: Thiotepa, Etoposide Day -2: Rest Day -1: Rest Day 0: Re-infusion of blood cells

Drug: Single Cycle Intensive Chemotherapy

Tandem 3 Cycle Intensive Chemotherapy

EXPERIMENTAL

The 2 drugs to be used in this treatment are thiotepa and carboplatin. These drugs will be given over 2 days to help kill the cancer cells. After 72 hours from getting these drugs, previously collected and frozen blood cells will be thawed and returned through the venous catheter. Day -4: Thiotepa, Carboplatin Day -3: Thiotepa, Carboplatin Day -2: Rest Day -1: Rest Day 0: Re-infusion of blood cells. Following recovery from the first cycle of this chemotherapy, about 28 days following the Day 0 reinfusion of blood cells, the same cycle will be repeated again. A total of 3 cycles of this therapy will be administered, over the course of 12 weeks.

Drug: Tandem 3 Cycle Intensive Chemotherapy

Interventions

Induction DRUG

vincristine, cisplatin, cyclophosphamide, etoposide, high-dose methotrexate

Also known as: vincristine, cisplatin, cyclophosphamide, etoposide, high-dose methotrexate

Induction

Single Cycle Intensive Chemotherapy DRUG

Carboplatin, thiotepa, etoposide

Also known as: Carboplatin, thiotepa, etoposide

Single Cycle Intensive Chemotherapy

Tandem 3 Cycle Intensive Chemotherapy DRUG

Carboplatin, thiotepa

Also known as: Carboplatin, thiotepa

Tandem 3 Cycle Intensive Chemotherapy

Eligibility Criteria

• Age: Up to 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients 10 years of age at the time of definitive confirmatory eligible histologic or cytologic diagnosis of eligible CNS tumor (brain or spinal cord)
• Patients may not have received irradiation or chemotherapy (except corticosteroids)
• Have histologically proven diagnosis of medulloblastoma or CNS embryonal tumors of the brain or spinal cord
• Medulloblastoma
• Posterior fossa classic, desmoplastic or extensive nodular or anaplastic/large cell medulloblastoma with appropriate and sufficient tumor material (FFPE or snap frozen) for proposed assays: all stages, age less than 6 years at diagnosis
• Posterior fossa classic or anaplastic/large cell medulloblastoma with sufficient tumor material (FFPE or snap frozen) for proposed assays: clinically high-stage (neuraxis or extra-neural dissemination, M1-4), age greater than 6 years to less than 10 years at diagnosis
• Posterior fossa medulloblastoma, those 6 years of age and above at diagnosis, will only be eligible if they have evidence of neuraxis or extraneural dissemination. Patients 6 years of age and above with low-stage (standard-risk, M0) medulloblastoma will NOT be eligible for this study, irrespective of molecular subgroup and extend of local resection
• CNS Embryonal Tumors:
• \- Pineoblastoma, CNS neuroblastoma, CNS ganglioneuroblastoma, embryonal tumor with multi-layered rosettes (ETMR, including embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma and ETMR not otherwise specified), medulloepithelioma, CNS embryonal tumor with rhabdoid features (INI1 intact) and CNS embryonal tumor, not otherwise specified.
• Must commence Induction chemotherapy within 28 days of the most recent definitive surgical procedure and within 21 days of the most recent neuro-imaging studies (MRI of brain, performed with and without gadolinium contrast, and MRI of total spine, performed with gadolinium contrast) and lumbar CSF cytological examination
• Patients must have adequate organ functions at the time of registration:
• Liver: bilirubin less than 1.5 mg/dL (except for patients with Gilbert's Syndrome of indirect hyperbilirubinemia) and transaminases \[SGPT or ALT, and SGOT or AST\] less than 2.5 (two and a half) times the upper limits of institutional normal.
• Renal: Creatinine clearance and/or glomerular filtration rate (GFR) greater than or equal to 60 mL/min/1.73m² within 21 days of protocol therapy.
• Bone Marrow Function:
• Peripheral absolute phagocyte count (APC) \> 1000/ µL. APC = numbers of banded neutrophils + segmented neutrophils + metamyelocytes + monocytes + eosinophils Please note, if institution reports differential as a percentage, then APC = \[percentage of banded neutrophils + segmented neutrophils+ metamyelocytes+monocytes+eosinophils\] x total white cell count.

You may not qualify if:

• Patients older than 10 years of age at time of diagnosis
• Following diagnoses are not eligible for study enrollment: CNS atypical teratoid/rhabdoid tumor (AT/RT); all ependymomas including anaplastic ependymomas of the brain or spinal cord; all choroid plexus carcinomas; all high-grade glial and glio-neuronal tumors; all primary CNS germ cell tumors; all primary CNS sarcomas; all primary or metastatic CNS lymphomas and solid leukemic lesions (i.e., chloromas, granulocytic sarcomas).
• Patients with unbiopsied diffuse intrinsic pontine tumors will NOT be eligible for this study.

Sponsors & Collaborators

• Parth Patel: lead
• Children's of Alabama: collaborator

Study Sites (62)

Children's of Alabama

Birmingham, Alabama, 35233, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92350, United States

Location

Memorial Care Health Services

Long Beach, California, 90806, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Mattel Children's Hospital (UCLA)

Los Angeles, California, 90095, United States

Location

UCSF Oakland Benioff

Oakland, California, 94609, United States

Location

Children's Hospital Orange County

Orange, California, 91868, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Nemours Center for Cancer and Blood Disorders

Wilmington, Delaware, 19803, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Shands Children's Hospital/ University of FL

Gainesville, Florida, 32608, United States

Location

Nemours Center for Cancer and Blood Disorders

Jacksonville, Florida, 19803, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Orlando Health

Orlando, Florida, 32806, United States

Location

John's Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30342, United States

Location

Riley Children's Hospital/University of Indiana

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Louisville School of Medicine

Louisville, Kentucky, 40202, United States

Location

John's Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Central Michigan University

Detroit, Michigan, 48201, United States

Location

Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

Children's Hospital of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Masonic Children's Hospital/University of Minnesota

Minneapolis, Minnesota, 55454, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Children's Specialty Care of Nevada

Las Vegas, Nevada, 89135, United States

Location

Joseph Sanzari Children's Hospital/ Hackensack University

Hackensack, New Jersey, 07601, United States

Location

Morristown Medical Center, Atlantic Health System

Morristown, New Jersey, 07960, United States

Location

New York Medical College

Hawthorne, New York, 10532, United States

Location

Northwell Health

Hempstead, New York, 11549, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Columbia Presbyterian Children's Hospital

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Upstate Golisano Children's Hospital/ SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Carolina's HealthCare System/Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Rainbow Babies & Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Dayton Children's Hospital

Dayton, Ohio, 45404, United States

Location

Penn State Hershey Children's Hospital

Hershey, Pennsylvania, 17033, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23219, United States

Location

American Family Children's Hospital/University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 58226, United States

Location

B.C. Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

Alberta Children's Hospital

Calgary, Canada

Location

Stollery Children's Hospital

Edmonton, Canada

Location

Hamilton Health/McMasters Children's Hospital, Hamilton, Canada

Hamilton, Canada

Location

The Hospital of Sick Children

Toronto, Canada

Location

Starship Children's Hospital

Auckland, New Zealand

Location

Christchurch Children's Hospital

Christchurch, New Zealand

Location

MeSH Terms

Conditions

Medulloblastoma

Interventions

Neoadjuvant Therapy; Vincristine; Cisplatin; Cyclophosphamide; Etoposide; Methotrexate; Carboplatin; Thiotepa

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

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Aminopterin; Pterins; Pteridines; Coordination Complexes; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring

Study Officials

• Randal Olshefski, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

• Jonathan Finlay, MD

  Global Neuro-Oncology, Inc.

  STUDY CHAIR

• Girish Dhall, MD

  Children's of Alabama at UAB

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: April 27, 2016
• First Posted: August 23, 2016
• Study Start: September 1, 2015
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

US (55); NZ (2); CA (5)