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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02875314




Registration number
NCT02875314
Ethics application status
Date submitted
27/04/2016
Date registered
23/08/2016
Date last updated
13/05/2024

Titles & IDs
Public title
HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors
Scientific 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
Secondary ID [1] 0 0
IRB15-00399
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Medulloblastoma 0 0
Central Nervous System Embryonal Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Testicular
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Induction
Treatment: Drugs - Single Cycle Intensive Chemotherapy
Treatment: Drugs - Tandem 3 Cycle Intensive Chemotherapy

Experimental: Induction - 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.

Experimental: Single Cycle Intensive Chemotherapy - 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

Experimental: Tandem 3 Cycle Intensive Chemotherapy - 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.


Treatment: Drugs: Induction
vincristine, cisplatin, cyclophosphamide, etoposide, high-dose methotrexate

Treatment: Drugs: Single Cycle Intensive Chemotherapy
Carboplatin, thiotepa, etoposide

Treatment: Drugs: Tandem 3 Cycle Intensive Chemotherapy
Carboplatin, thiotepa
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Compare tandem consolidation vs. single cycle consolidation A
Timepoint [1] 0 0
5 years
Primary outcome [2] 0 0
Compare tandem consolidation vs. single cycle consolidation B
Timepoint [2] 0 0
5 years
Secondary outcome [1] 0 0
Induction Cycle Reduction
Timepoint [1] 0 0
5 years
Secondary outcome [2] 0 0
Uniform Treatment Regimen
Timepoint [2] 0 0
5 years
Secondary outcome [3] 0 0
Therapy-Related Hearing Loss Evaluation A
Timepoint [3] 0 0
5 years
Secondary outcome [4] 0 0
Therapy-Related Hearing Loss Evaluation B
Timepoint [4] 0 0
5 years
Secondary outcome [5] 0 0
Neuropsychological effects will be evaluated using age based tests and questionnaires.
Timepoint [5] 0 0
5 years
Secondary outcome [6] 0 0
Endocrine studies will be conducted using Serum-free T4, TSH, Cortisol, IGF and IGFBP3 laboratory tests.
Timepoint [6] 0 0
5 years
Secondary outcome [7] 0 0
Physical growth will be evaluated by collecting patient's height, weight and BSA.
Timepoint [7] 0 0
5 years
Secondary outcome [8] 0 0
The development of second neoplasms will be monitored.
Timepoint [8] 0 0
5 years
Secondary outcome [9] 0 0
Neuropathology Biorepository and Clinical Database
Timepoint [9] 0 0
5 years

Eligibility
Key inclusion criteria
- 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:

1. 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.

2. Platelet Count > 100,000/µL (transfusion independent)

3. Hemoglobin > 8 gm/dL (may have received RBC transfusions).
Minimum age
No limit
Maximum age
10 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2030
Actual
Sample size
Target
250
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Delaware
Country [7] 0 0
United States of America
State/province [7] 0 0
District of Columbia
Country [8] 0 0
United States of America
State/province [8] 0 0
Florida
Country [9] 0 0
United States of America
State/province [9] 0 0
Georgia
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United States of America
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Indiana
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Iowa
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United States of America
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Kentucky
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United States of America
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Maryland
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United States of America
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Massachusetts
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Michigan
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Minnesota
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United States of America
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Missouri
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Nevada
Country [19] 0 0
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New Jersey
Country [20] 0 0
United States of America
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New York
Country [21] 0 0
United States of America
State/province [21] 0 0
North Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
Ohio
Country [23] 0 0
United States of America
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Pennsylvania
Country [24] 0 0
United States of America
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South Carolina
Country [25] 0 0
United States of America
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Tennessee
Country [26] 0 0
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Texas
Country [27] 0 0
United States of America
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Utah
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United States of America
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Virginia
Country [29] 0 0
United States of America
State/province [29] 0 0
Wisconsin
Country [30] 0 0
Canada
State/province [30] 0 0
British Columbia
Country [31] 0 0
Canada
State/province [31] 0 0
Calgary
Country [32] 0 0
Canada
State/province [32] 0 0
Edmonton
Country [33] 0 0
Canada
State/province [33] 0 0
Hamilton
Country [34] 0 0
Canada
State/province [34] 0 0
Toronto
Country [35] 0 0
New Zealand
State/province [35] 0 0
Auckland
Country [36] 0 0
New Zealand
State/province [36] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Other
Name
Parth Patel
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Children's of Alabama
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02875314
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Randal Olshefski, MD
Address 0 0
Nationwide Children's Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries