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Brain and Central Nervous System TumorsPhase 3NCT00392886

Combination Chemotherapy With or Without Etoposide Followed By an Autologous Stem Cell Transplant in Treating Young Patients With Previously Untreated Malignant Brain Tumors

A Phase 3 study testing carboplatin, cisplatin and cyclophosphamide in people with Brain and Central Nervous System Tumors, run by Children's Hospital Los Angeles at 37 sites in 5 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. A bone marrow or peripheral stem cell transplant using stem cells from the patient may be able to replace blood-forming cells that were destroyed by… Read more about this study

Who is it for?
Ages Up to 10 years
Conditions the study is for
Brain and Central Nervous System Tumors
What is being tested?
carboplatin, cisplatin and cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
37 sitesin 5 countries
Study dates
Mar 2004to Dec 2010
Phase
Phase 3
Are there results?
None posted in the registry

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed malignant brain tumor, including any of the following:
  • Posterior fossa medulloblastoma/primitive neuroectodermal tumor (PNET)*
  • All stages allowed
  • Must be < 4 years of age at diagnosis unless there is evidence of postoperative residual tumor (> 1.5 cm² tumor area) or evidence of neuraxis or extraneural dissemination (high-stage)
  • Medulloblastoma, cerebral neuroblastoma, and ependymoblastoma allowed
  • Low-stage (standard-risk) medulloblastoma not allowed in patients > 4 years of age
  • Ependymoma*
  • All stages and locations allowed
  • Cellular and anaplastic subtypes allowed (no myxopapillary ependymomas of the spinal cord)
  • Must be < 36 months of age at diagnosis for posterior fossa tumor OR < 72 months of age for supratentorial tumor
  • Evidence of neuraxis dissemination irrespective of primary site
  • No cellular (low-grade) supratentorial ependymomas at any age with complete resection of parenchymally based (i.e., not periventricular) supratentorial tumors
  • Brain stem tumor*
  • All stages allowed irrespective of extent of resection
  • No unbiopsied diffuse intrinsic pontine tumor
  • Tumor pathologically confirmed to be either malignant glioma or PNET allowed
  • High-grade glioma**
  • Primary atypical teratoid/rhabdoid tumor of the CNS*
  • Choroid plexus carcinoma or atypical choroid plexus papilloma*
  • All stages and locations allowed
  • Anaplastic astrocytoma**
  • Glioblastoma multiforme**
  • Anaplastic oligodendroglioma**
  • Anaplastic ganglioglioma**
  • Other anaplastic mixed gliomas**
  • Small-cell glioblastoma**
  • Giant-cell glioblastoma**
  • Gliosarcoma**
  • The following diagnoses or subtypes are not allowed:
  • Choroid plexus papilloma
  • Pineocytoma
  • Low-grade mixed glioma
  • Primary CNS germ cell tumor
  • Primary CNS lymphoma
  • Solid leukemic lesions (i.e., chloromas, granulocytic sarcomas)
  • Pleomorphic xanthoastrocytoma, low grade
  • Desmoplastic ganglioglioma
  • Low-grade astrocytoma
  • Previously untreated disease
  • Has undergone definitive surgery within the past 42 days NOTE: *Patients receive treatment according to regimen D2

NOTE: **Patients receive treatment according to regimen C

PATIENT CHARACTERISTICS:

  • Bilirubin < 1.5 mg/dL
  • ALT and AST < 2.5 times upper limit of normal
  • Creatinine clearance and/or glomerular filtration rate ≥ 60 mL/min

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior radiotherapy or chemotherapy
  • Prior corticosteroids allowed
  • No concurrent corticosteroids for antiemesis only
  • No concurrent brachytherapy or electron radiotherapy
  • No concurrent dairy products or grapefruit juice with temozolomide administration

Trial locations and contacts

37 sites in 5 countries.

37 sites in 5 countries

United States29 sites

  • Children's Memorial Hospital - Chicago

    Chicago, Illinois, 60614

  • University of Chicago Comer Children's Hospital

    Chicago, Illinois, 60637

  • Rainbow Babies and Children's Hospital

    Cleveland, Ohio, 44106

  • Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205-2696

  • Helen DeVos Children's Hospital at Spectrum Health

    Grand Rapids, Michigan, 49503

  • Tomorrows Children's Institute at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Penn State Children's Hospital

    Hershey, Pennsylvania, 17033

  • M. D. Anderson Cancer Center at University of Texas

    Houston, Texas, 77030-4009

  • Riley's Children Cancer Center at Riley Hospital for Children

    Indianapolis, Indiana, 46202-5225

  • Nemours Children's Clinic

    Jacksonville, Florida, 32207-8482

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • Loma Linda University Cancer Institute at Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Jonathan Jaques Children's Cancer Center at Miller Children's Hospital

    Long Beach, California, 90806

  • Childrens Hospital Los Angeles

    Los Angeles, California, 90027

  • Mattel Children's Hospital at UCLA

    Los Angeles, California, 90095

  • Kosair Children's Hospital

    Louisville, Kentucky, 40232

  • Masonic Cancer Center at University of Minnesota

    Minneapolis, Minnesota, 55455

  • Schneider Children's Hospital

    New Hyde Park, New York, 11040

  • NYU Cancer Institute at New York University Medical Center

    New York, New York, 10016

  • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

    New York, New York, 10032

  • Children's Hospital and Research Center Oakland

    Oakland, California, 94609

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Phoenix Children's Hospital Outpatient Center

    Phoenix, Arizona, 85016

  • SUNY Upstate Medical University Hospital

    Syracuse, New York, 13210

  • Albert Einstein Cancer Center at Albert Einstein College of Medicine

    The Bronx, New York, 10461

  • Toledo Children's Hospital

    Toledo, Ohio, 43601

  • St. Vincent Mercy Medical Center

    Toledo, Ohio, 43608

  • Alfred I. duPont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

Canada3 sites

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • Children's & Women's Hospital of British Columbia

    Vancouver, British Columbia, V6H 3V4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

New Zealand2 sites

  • Christchurch Hospital

    Christchurch, 1

  • Wellington Children's Hospital

    Wellington, 6002

Other trials in New Zealand

Switzerland2 sites

  • Swiss Pediatric Oncology Group Bern

    Bern, CH 3010

  • Universitaets Kinderklinik

    Bern, CH-3010

Other trials in Switzerland

Australia1 site

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6001

Other trials in Australia

About this study

Official title: Dose Intensive Chemotherapy for Children Less Than Ten Years of Age Newly-Diagnosed With Malignant Brain Tumors: A Pilot Study of Two Alternative Intensive Induction Chemotherapy Regimens, Followed by Consolidation With Myeloablative Chemotherapy (Thiotepa and Carboplatin, With or Without Etoposide) and Autologous Stem Cell Rescue [HEAD START III]

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. A bone marrow or peripheral stem cell transplant using stem cells from the patient may be able to replace blood-forming cells that were destroyed by chemotherapy. This may allow more chemotherapy to be given so that more tumor cells are killed.

PURPOSE: This phase III trial is studying how well giving combination chemotherapy with or without etoposide followed by an autologous stem cell transplant works in treating young patients with previously untreated malignant brain tumors.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the 2-year event-free survival (EFS) and overall survival (OS) of pediatric patients with previously untreated nondisseminated medulloblastoma (< 4 years of age), disseminated medulloblastoma (< 10 years of age), or noncerebellar primitive neuroectodermal tumors (PNET) (disseminated or non-disseminated) treated with induction chemotherapy followed by consolidation with myeloablative chemotherapy and autologous hematopoietic stem cell rescue.
  • Determine the toxicity of this regimen in these patients.
  • Determine the mortality of patients treated with this regimen.

Secondary

  • Determine the complete and partial response rates after completion of induction chemotherapy in these patients stratified according to pathology (medulloblastoma vs noncerebellar PNET vs high-grade gliomas vs atypical teratoid/rhabdoid tumors vs choroid plexus carcinomas and atypical papillomas vs ependymomas).
  • Describe the EFS and OS of these patients stratified according to additional diagnoses (atypical teratoid/rhabdoid tumors vs choroid plexus carcinomas and atypical choroid plexus papillomas vs ependymomas vs high-grade gliomas).
  • Describe the time to progression and patterns of relapse in these patients stratified by diagnosis and radiotherapy received (< 6 years of age with evidence of no residual tumor pre-transplant and no post-transplant consolidation radiotherapy vs < 6 years of age with residual tumor present pre-transplant treated with post-transplant consolidation radiotherapy vs > 6 years of age treated with post-transplant consolidation radiotherapy).
  • Determine the neuropsychometric function, endocrinologic function, and physical growth in these patients stratified according to radiotherapy received (none vs reduced-volume craniospinal radiotherapy vs focused local-field radiotherapy).

OUTLINE: This is a pilot study. Patients are stratified according to type of tumor (nonglial vs glial and diffuse pontine).

  • Regimen C (patients with glial tumors):
  • Stem cell harvesting (bone marrow and/or peripheral blood): Patients undergo leukapheresis or bone marrow aspiration to collect bone marrow or peripheral blood stem cells prior to beginning induction chemotherapy or after the first course of induction chemotherapy.
  • Induction chemotherapy: Patients receive vincristine IV on days 1, 8, and 15 of courses 1-3, oral temozolomide once daily on days 1-5, and carboplatin IV over 4 hours on days 1 and 2. Patients also receive G-CSF SC beginning on day 6 and continuing until blood counts recover. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients with unresectable bulky disease and corticosteroid dependence are removed from study. All other patients proceed to consolidation chemotherapy.

  • Consolidation chemotherapy: Patients receive carboplatin IV over 4 hours on days -8 to -6 and thiotepa IV over 3 hours on days -5 to -3.
  • Autologous bone marrow or peripheral blood stem cell transplantation: Patients undergo reinfusion of bone marrow or peripheral blood stem cells on day 0. Patients also receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
  • Radiotherapy: Beginning within 6 weeks after stem cell transplantation, patients > 6 years of age at diagnosis undergo radiotherapy once daily 5 days a week for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients ≤ 6 years of age undergo radiotherapy if there is evidence of tumor remaining after completion of induction chemotherapy.
  • Regimen D2 (patients with nonglial tumors):
  • Stem cell harvesting (bone marrow and/or peripheral blood): Patients undergo leukapheresis or bone marrow aspiration to collect bone marrow or peripheral blood stem cells prior to beginning induction chemotherapy or after the first course of induction chemotherapy.
  • Induction chemotherapy:
  • Courses 1, 3, and 5 (28 days per course): Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour and etoposide IV over 2 hours on days 2 and 3, high-dose methotrexate IV over 4 hours on day 4, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until blood counts recover. Patients also receive vincristine IV on days 1, 8, and 15 of courses 1 and 3.
  • Courses 2 and 4 (28 days per course): Patients receive oral temozolomide once daily on days 1-5, oral etoposide once daily on days 1-10, cyclophosphamide IV over 1 hour on days 11 and 12, and G-CSF SC beginning on day 13 and continuing until blood counts recover. Patients also receive vincristine IV on days 1, 8, and 15 of course 2.

Patients with unresectable bulky disease and corticosteroid dependence are removed from study. All other patients proceed to consolidation chemotherapy.

  • Consolidation chemotherapy: Patients receive carboplatin IV over 4 hours on days -8 to -6 and thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3.
  • Autologous bone marrow or peripheral blood stem cell transplantation: Patients undergo re-infusion of bone marrow or peripheral blood stem cells on day 0. Patients also receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
  • Radiotherapy:Patients undergo radiotherapy as in regimen C. Patients in both regimens undergo neuropsychological testing after induction chemotherapy but before consolidation chemotherapy and then at 18, 36, and 54 months after completion of study treatment. Neuropsychometric and neuroendocrine testing is performed before and after radiotherapy. Quality of life is also assessed periodically.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.

Keywords
untreated childhood medulloblastoma, untreated childhood supratentorial primitive neuroectodermal tumor, childhood infratentorial ependymoma, childhood supratentorial ependymoma, newly diagnosed childhood ependymoma, childhood high-grade cerebral astrocytoma, childhood oligodendroglioma, childhood atypical teratoid/rhabdoid tumor, childhood choroid plexus tumor, untreated childhood cerebellar astrocytoma, untreated childhood visual pathway and hypothalamic glioma, untreated childhood pineoblastoma
Medical subject headings
Central Nervous System Neoplasms, Astrocytoma, Oligodendroglioma, Rhabdoid Tumor, Choroid Plexus Neoplasms

What participants receive

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

Study groups in NCT00392886
Study groupRoleWhat they receive
Regimen CExperimentalPatients receive induction therapy of vincristine IV on days 1, 8, and 15 of courses 1-3, oral temozolomide once daily on days 1-5, and carboplatin IV over 4 hours on days 1 and 2. Patients also receive G-CSF SC beginning on day 6 and continuing until blood counts recover. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive consolidation therapy of carboplatin IV over 4 hours on days -8 to -6 and thiotepa IV over 3 hours on days -5 to -3, undergo reinfusion of bone marrow or peripheral blood stem cells on day 0, and receive G-CSF SC beginning on day 1 and continuing until blood counts recover. Beginning within 6 weeks after transplantation, some patients undergo radiotherapy once daily 5 days a week for 4-6 weeks in the absence of disease progression or unacceptable toxicity and some patients undergo radiotherapy if there is evidence of tumor remaining after completion of induction chemotherapy.
Receives: Drug: carboplatin; Drug: temozolomide; Drug: thiotepa; Drug: vincristine sulfate; Procedure: autologous bone marrow transplantation; Procedure: autologous hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy
Regimen D2ExperimentalIn courses 1, 3, and 5, patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour and etoposide IV over 2 hours on days 2 and 3, high-dose methotrexate IV over 4 hours on day 4, vincristine IV on days 1, 8, and 15 (in courses1 and 3), and filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until blood counts recover. In courses 2 and 4, patients receive oral temozolomide once daily on days 1-5, oral etoposide once daily on days 1-10, cyclophosphamide IV over 1 hour on days 11 and 12, vincristine IV on days 1, 8, and 15 (in course 2), and G-CSF SC beginning on day 13 and continuing until blood counts recover. Patients receive consolidation therapy as in regimen C in combination with etoposide IV over 3 hours on days -5 to -3 and undergo autologous bone marrow or peripheral blood stem cell transplantation, receive G-CSF, and undergo radiotherapy as in regimen C.
Receives: Drug: carboplatin; Drug: cisplatin; Drug: cyclophosphamide; Drug: etoposide; Drug: methotrexate; Drug: temozolomide; Drug: thiotepa; Drug: vincristine sulfate; Procedure: autologous bone marrow transplantation; Procedure: autologous hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy

What is being measured

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

  1. Time to tumor progression, disease recurrence, or death of any cause

  2. Event-free survival at 2 years

  3. Toxicity

Secondary outcomes (3)

  1. Response to induction as assessed by one-time tumor measurements at baseline and after completion of induction chemotherapy

  2. Time to death

  3. Overall survival

Timeline

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

  1. First posted26 Oct 2006 (estimated)
  2. Study startMar 2004
  3. Primary completionDec 2010 (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 3
Primary purpose
Treatment
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00392886
Sponsor's protocol ID
CDR0000503990
Other IDs
CHLA-HEAD-START-III, CHLA-HSIII, CHLA-2004-020, CHLA-04.020, UMN-MT2004-06
Status last verified
Oct 2010
First submitted
25 Oct 2006
Last updated
18 Dec 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing carboplatin, cisplatin and cyclophosphamide in people with Brain and Central Nervous System Tumors, run by Children's Hospital Los Angeles at 37 sites in 5 countries.

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

Who may be eligible to take part?

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: status not confirmed, as of the sponsor's last update on 18 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in United States, Canada, New Zealand, Switzerland, Australia. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Results are not available in the source record.

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?

Time to tumor progression, disease recurrence, or death of any cause. The study lists 3 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 NCT00392886.

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 18 Dec 2013.

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