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MedulloblastomaPhase 4NCT02875314

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

A Phase 4 study testing Induction, Single Cycle Intensive Chemotherapy and Tandem 3 Cycle Intensive Chemotherapy in people with Medulloblastoma and Central Nervous System Embryonal Tumors, run by Parth Patel at 62 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages Up to 10 years
What is being tested?
Induction, Single Cycle Intensive Chemotherapy and Tandem 3 Cycle Intensive Chemotherapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
250 participants
Where
62 sitesin 3 countries
Study dates
Sep 2015to Dec 2030
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 10 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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
Show all 17Show fewer
  • 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.
  • Platelet Count > 100,000/µL (transfusion independent)
  • Hemoglobin > 8 gm/dL (may have received RBC transfusions).

Who cannot join

  • 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.

Trial locations and contacts

62 sites in 3 countries.

62 sites in 3 countries

United States55 sites

  • Akron Children's Hospital

    Akron, Ohio, 44308

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30342

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • John's Hopkins University School of Medicine

    Baltimore, Maryland, 21287

  • Children's of Alabama

    Birmingham, Alabama, 35233

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Carolina's HealthCare System/Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • Rainbow Babies & Children's Hospital

    Cleveland, Ohio, 44106

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • Central Michigan University

    Detroit, Michigan, 48201

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Shands Children's Hospital/ University of FL

    Gainesville, Florida, 32608

  • Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • Joseph Sanzari Children's Hospital/ Hackensack University

    Hackensack, New Jersey, 07601

  • New York Medical College

    Hawthorne, New York, 10532

  • Northwell Health

    Hempstead, New York, 11549

  • Penn State Hershey Children's Hospital

    Hershey, Pennsylvania, 17033

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Riley Children's Hospital/University of Indiana

    Indianapolis, Indiana, 46202

  • University of Iowa Hospital and Clinics

    Iowa City, Iowa, 52242

  • Nemours Center for Cancer and Blood Disorders

    Jacksonville, Florida, 19803

  • Children's Specialty Care of Nevada

    Las Vegas, Nevada, 89135

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202

  • Loma Linda University Medical Center

    Loma Linda, California, 92350

  • Memorial Care Health Services

    Long Beach, California, 90806

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Mattel Children's Hospital (UCLA)

    Los Angeles, California, 90095

  • University of Louisville School of Medicine

    Louisville, Kentucky, 40202

  • American Family Children's Hospital/University of Wisconsin

    Madison, Wisconsin, 53792

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 58226

  • Children's Hospital of Minnesota

    Minneapolis, Minnesota, 55404

  • Masonic Children's Hospital/University of Minnesota

    Minneapolis, Minnesota, 55454

  • Morristown Medical Center, Atlantic Health System

    Morristown, New Jersey, 07960

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • NYU Langone Medical Center

    New York, New York, 10016

  • Columbia Presbyterian Children's Hospital

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • UCSF Oakland Benioff

    Oakland, California, 94609

  • Children's Hospital Orange County

    Orange, California, 91868

  • Orlando Health

    Orlando, Florida, 32806

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

  • Virginia Commonwealth University

    Richmond, Virginia, 23219

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • John's Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

  • Upstate Golisano Children's Hospital/ SUNY Upstate Medical University

    Syracuse, New York, 13210

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Nemours Center for Cancer and Blood Disorders

    Wilmington, Delaware, 19803

Other trials in United States

Canada5 sites

  • Alberta Children's Hospital

    Calgary

  • Stollery Children's Hospital

    Edmonton

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

    Hamilton

  • The Hospital of Sick Children

    Toronto

  • B.C. Children's Hospital

    Vancouver, British Columbia, V6H 3V4

Other trials in Canada

New Zealand2 sites

  • Starship Children's Hospital

    Auckland

  • Christchurch Children's Hospital

    Christchurch

Other trials in New Zealand

About this study

Official title: HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors Clinical and Molecular Risk-Tailored Intensive and Compressed Induction Chemotherapy Followed by Consolidation With Randomization to Either Single Cycle or to Three Tandem Cycles of Marrow-Ablative Chemotherapy With Autologous Hematopoietic Progenitor Cell Rescue

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.

Read the detailed description

Due to the inferior response and event-free survival data of Regimens D and D2 on "Head Start III" for all children with supratentorial embryonal tumors, in comparison with the published data from "Head Start II" with Regimen A2 for metastatic patients, all such patients will receive the "Head Start II" Induction Regimen A2, on "Head Start 4", for either three or five cycles, depending upon whether or not they achieve complete remission by the end of Induction cycle #3. They will then undergo randomization to either single cycle or three tandem cycles of Consolidation marrow-ablative chemotherapy with AuHPCR.

Because of the unsatisfactory event-free survival for young children with non-desmoplastic/extensive nodular medulloblastoma (predominantly non-Shh and non-Wnt medulloblastoma subgroups) on Regimens D and D2 of "Head Start III", all these patients will receive the "Head Start II" Induction Regimen A2 on ""Head Start 4"", for either three or five cycles, depending upon whether or not they achieve complete remission by the end of Induction cycle #3. They will then undergo randomization to either single cycle or three tandem cycles of Consolidation marrow-ablative chemotherapy with AuHPCR.

Because of the excellent event-free and overall survival for young children with good risk medullo-blastoma (Shh or Wnt subgroups) treated with up-front "Head Start" chemotherapy strategies, such patients will undergo risk-tailored reduction of duration of Induction therapy from five cycles to three cycles of the "Head Start II" Induction Regimen A2 on "Head Start 4" for patients achieving a complete response to 3 cycles, followed, provided they are also without evidence of residual tumor following recovery from Induction cycle #3. They will NOT then undergo randomization, but will follow with a single cycle of Consolidation marrow-ablative chemotherapy as in "Head Start" studies.

Being tested
Induction, Single Cycle Intensive Chemotherapy, Tandem 3 Cycle Intensive Chemotherapy
Medical subject headings
Medulloblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • InductionDrug

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

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

  • Single Cycle Intensive ChemotherapyDrug

    Also called Carboplatin, thiotepa, etoposide

    Carboplatin, thiotepa, etoposide

  • Tandem 3 Cycle Intensive ChemotherapyDrug

    Also called Carboplatin, thiotepa

    Carboplatin, thiotepa

Study groups in NCT02875314
Study groupRoleWhat they receive
InductionExperimentalThe 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.
Receives: Drug: Induction
Single Cycle Intensive ChemotherapyExperimentalThe 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
Receives: Drug: Single Cycle Intensive Chemotherapy
Tandem 3 Cycle Intensive ChemotherapyExperimentalThe 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.
Receives: Drug: Tandem 3 Cycle Intensive Chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 5 years

  2. 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.

    Measured: 5 years

Secondary outcomes (9)

  1. Induction Cycle Reduction

    Induction chemotherapy cycles will be reduced in number from five to three for molecularly high-risk medulloblastoma (non-Shh/non-Wnt) and CNS embryonal tumors who achieve a complete response (CR) after three cycles of Induction therapy results in equivalent 3-year EFS. Outcome will be analyzed irrespective of Consolidation assignment (Primary Aim) and compared to historical controls.

    Measured: 5 years

  2. Uniform Treatment Regimen

    Assess the rate of response of sequential dose-intensive and dose-compressed Induction chemotherapy followed by marrow-ablative chemotherapy and autologous hematopoietic progenitor cell rescue (AuHPCR) for children with medulloblastoma and other CNS embryonal tumors enrolled on the "Head Start 4" study utilizing a uniform treatment regimen.

    Measured: 5 years

  3. Therapy-Related Hearing Loss Evaluation A

    The prevalence and severity of therapy-related hearing loss as a function of cumulative dosing of cisplatin (three versus five cycles during Induction) will be evaluated. Distortion-Product Oto-acoustic Emissions (DPOAE) will be used as an early predictor of hearing loss to identify at-risk patients.

    Measured: 5 years

  4. Therapy-Related Hearing Loss Evaluation B

    The prevalence and severity of therapy-related hearing loss as a function of AuHPCR (one versus three tandem transplants in Consolidation) will be evaluated. Distortion-Product Oto-acoustic Emissions (DPOAE) will be used as an early predictor of hearing loss to identify at-risk patients.

    Measured: 5 years

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

    The long-term neuropsychological effects will be evaluated.

    Measured: 5 years

  6. Endocrine studies will be conducted using Serum-free T4, TSH, Cortisol, IGF and IGFBP3 laboratory tests.

    The long-term endocrine functions effect will be evaluated.

    Measured: 5 years

  7. Physical growth will be evaluated by collecting patient's height, weight and BSA.

    The long-term physical growth effect will be evaluated.

    Measured: 5 years

  8. The development of second neoplasms will be monitored.

    The long-term development of second neoplasms will be evaluated.

    Measured: 5 years

  9. Neuropathology Biorepository and Clinical Database

    The study will establish a "Head Start 4" repository of clinical, radiographic and biologic specimens, including nucleic acids derived from these specimens, for future genomic, biologic and pharmacologic research.

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Aug 2016 (estimated)
  2. Study startSep 2015
  3. Primary completionDec 2030 (estimated)
  4. Study completionDec 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
250 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02875314
Sponsor's protocol ID
IRB15-00399
Status last verified
Jun 2026
First submitted
27 Apr 2016
Last updated
3 Jun 2026
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Induction, Single Cycle Intensive Chemotherapy and Tandem 3 Cycle Intensive Chemotherapy in people with Medulloblastoma and Central Nervous System Embryonal Tumors, run by Parth Patel at 62 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 62 sites in United States, Canada, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Compare tandem consolidation vs. single cycle consolidation A (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02875314.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2026.

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