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Brain TumorPhase 3NCT00078988

High-Dose Chemotherapy Plus Autologous Stem Cell Transplantation Compared With Intermediate-Dose Chemotherapy Plus Autologous Stem Cell Transplantation With or Without Isotretinoin in Treating Young Patients With Recurrent High-Grade Gliomas

A Phase 3 study testing filgrastim, carboplatin and etoposide in people with Brain Tumor and Central Nervous System Tumor, run by Children's Oncology Group at 59 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

RATIONALE: Drugs used in chemotherapy, such as carboplatin, thiotepa, and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor… Read more about this study

Who is it for?
Ages Up to 20 years
Conditions the study is for
Brain Tumor, Central Nervous System Tumor
What is being tested?
filgrastim, carboplatin and etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
59 sitesin 3 countries
Study dates
Oct 2004to Sep 2006
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 20 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of 1 of the following high-grade gliomas:
  • Glioblastoma multiforme
  • Anaplastic astrocytoma
  • Gliosarcoma
  • Disease in first relapse
  • No primary brainstem or spinal cord gliomas
  • No secondary glioblastomas arising after prior treatment for a non-glial tumor
  • Prior local radiotherapy of 5,000-6,000 cGy required
  • Less than 1.5 cm of residual gadolinium-enhancing tumor in maximal cross-sectional diameter by MRI
  • No metastatic tumor by spinal MRI

PATIENT CHARACTERISTICS:

Age

  • Under 21 at diagnosis

Performance status

  • Lansky 50-100% OR
  • Karnofsky 50-100%

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 500/mm^3
  • Platelet count ≥ 100,000/mm^3 (transfusion independent)

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST or ALT < 2.5 times ULN

Renal

  • Glomerular filtration rate ≥ 60 mL/min AND/OR
  • Creatinine clearance ≥ 60 mL/min

Cardiovascular

  • Shortening fraction ≥ 27% by echocardiogram OR
  • Ejection fraction ≥ 50% by MUGA

Pulmonary

  • No dyspnea at rest
  • No exercise intolerance
  • Pulse oximetry > 94%

Other

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • More than 4 weeks since prior chemotherapy
  • No prior thiotepa
  • No prior myeloablative chemotherapy

Endocrine therapy

  • No concurrent corticosteroids

Radiotherapy

  • See Disease Characteristics
  • More than 8 weeks since prior radiotherapy
  • No prior craniospinal radiotherapy

Surgery

  • Not specified

Trial locations and contacts

59 sites in 3 countries.

59 sites in 3 countries

United States52 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308-1062

  • Emory University Hospital - Atlanta

    Atlanta, Georgia, 30322

  • CancerCare of Maine at Eastern Maine Medial Center

    Bangor, Maine, 04401

  • Floating Hospital for Children at Tufts - New England Medical Center

    Boston, Massachusetts, 02111

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263-0001

  • Hollings Cancer Center at Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3039

  • Rainbow Babies and Children's Hospital

    Cleveland, Ohio, 44106-5000

  • Columbus Children's Hospital

    Columbus, Ohio, 43205-2696

  • Children's Medical Center - Dayton

    Dayton, Ohio, 45404-1815

  • Children's Hospital Cancer Center

    Denver, Colorado, 80218-1088

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201-1379

  • INOVA Fairfax Hospital

    Fairfax, Virginia, 22031

  • Cook Children's Medical Center - Fort Worth

    Fort Worth, Texas, 76104-9958

  • University of Florida Shands Cancer Center

    Gainesville, Florida, 32610-0232

  • Spectrum Health Cancer Care - Butterworth Campus

    Grand Rapids, Michigan, 49503-2560

  • Van Elslander Cancer Center at St. John Hospital and Medical Center

    Grosse Pointe Woods, Michigan, 48236

  • Penn State Cancer Institute at Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Cancer Research Center of Hawaii

    Honolulu, Hawaii, 95813

  • Indiana University Cancer Center

    Indianapolis, Indiana, 46202-5289

  • St. Vincent Indianapolis Hospital

    Indianapolis, Indiana, 46260

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216-4505

  • Nemours Children's Clinic

    Jacksonville, Florida, 32207

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Kosair Children's Hospital

    Louisville, Kentucky, 40232

  • Covenant Children's Hospital

    Lubbock, Texas, 79410

  • University of Wisconsin Comprehensive Cancer Center

    Madison, Wisconsin, 53792-6164

  • Marshfield Clinic - Marshfield Center

    Marshfield, Wisconsin, 54449

  • University of Miami Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Miami Children's Hospital

    Miami, Florida, 33155

  • Children's Hospital of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • Fairview University Medical Center - University Campus

    Minneapolis, Minnesota, 55455

  • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

    New Brunswick, New Jersey, 08903

  • NYU Cancer Institute at New York University Medical Center

    New York, New York, 10016

  • Herbert Irving Comprehensive Cancer Center at Columbia University

    New York, New York, 10032

  • Children's Hospital of the King's Daughters

    Norfolk, Virginia, 23507-1971

  • Children's Hospital and Research Center - Oakland

    Oakland, California, 94609-1809

  • Oklahoma University Medical Center

    Oklahoma City, Oklahoma, 73104

  • Massey Cancer Center at Virginia Commonwealth University

    Richmond, Virginia, 23298-0037

  • James P. Wilmot Cancer Center at University of Rochester Medical Center

    Rochester, New York, 14642

  • University of California Davis Cancer Center

    Sacramento, California, 95817

  • Primary Children's Medical Center

    Salt Lake City, Utah, 84113-1100

  • Children's Hospital and Health Center - San Diego

    San Diego, California, 92123-4282

  • Sioux Valley Hospital and University of South Dakota Medical Center

    Sioux Falls, South Dakota, 57117-5039

  • Siteman Cancer Center at Barnes-Jewish Hospital

    St Louis, Missouri, 63110

  • All Children's Hospital

    St. Petersburg, Florida, 33701

  • SUNY Upstate Medical University Hospital

    Syracuse, New York, 13210

  • St. Joseph's Cancer Institute at St. Joseph's Hospital

    Tampa, Florida, 33607

  • New York Medical College

    Valhalla, New York, 10595

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010-2970

  • Kaplan Cancer Center at St. Mary's Medical Center

    West Palm Beach, Florida, 33407

Other trials in United States

Canada6 sites

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8N 3Z5

  • Montreal Children's Hospital at McGill University Health Center

    Montreal, Quebec, H3H 1P3

  • Hopital Sainte Justine

    Montreal, Quebec, H3T 1C5

  • Centre Hospitalier Universitaire de Quebec

    Ste-Foy, Quebec, G1V 4G2

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

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

    Vancouver, British Columbia, V6H 3V4

Other trials in Canada

Australia1 site

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6001

Other trials in Australia

About this study

Official title: A Phase III Randomized Trial for the Treatment of Pediatric High Grade Gliomas at First Recurrence With a Single High Dose Chemotherapy and Autologous Stem Cell Transplant Versus Three Courses of Intermediate Dose Chemotherapy With Peripheral Blood Stem Cell (PBSC) Support

RATIONALE: Drugs used in chemotherapy, such as carboplatin, thiotepa, and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Isotretinoin may be effective in preventing recurrence of glioma. It is not yet known which regimen of chemotherapy plus autologous stem cell transplantation with or without isotretinoin is more effective in treating recurrent high-grade glioma.

PURPOSE: This randomized phase III trial is studying high-dose chemotherapy or intermediate-dose chemotherapy followed by autologous stem cell transplantation to see how well it works compared to high-dose chemotherapy or intermediate-dose chemotherapy followed by autologous stem cell transplantation and isotretinoin in treating young patients with recurrent high-grade glioma.

Read the detailed description

OBJECTIVES:

  • Compare the event-free survival and overall survival of pediatric patients with recurrent high-grade gliomas treated with a single course of high-dose carboplatin, etoposide, and thiotepa and autologous stem cell transplantation vs multiple courses of intermediate-dose carboplatin and thiotepa and autologous stem cell transplantation with or without isotretinoin.
  • Compare the number of hospital days and time to engraftment in patients treated with these regimens.
  • Compare the toxic death rate in patients treated with these regimens.
  • Compare the tolerability of isotretinoin in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to pathologic diagnosis (glioblastoma multiforme vs anaplastic astrocytoma vs other high-grade glioma).

  • Chemotherapy and autologous stem cell reinfusion (ASCR): Patients are randomized to 1 of 2 treatment arms.
  • Arm I (high-dose chemotherapy and ASCR): Patients receive high-dose chemotherapy comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or subcutaneously (SC) once daily beginning on day 1 and continuing until blood counts recover. Autologous peripheral blood stem cells (PBSC) or bone marrow are reinfused on day 0.
  • Arm II (intermediate-dose chemotherapy and ASCR): Patients receive intermediate-dose chemotherapy comprising carboplatin IV over 4 hours and thiotepa IV over 3 hours on days 1-2 and G-CSF IV or SC once daily beginning on day 4 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 3. Treatment repeats every 28 days for a total of 3 courses.
  • Maintenance therapy: After recovery from chemotherapy (approximately day 30 post-transplantation), all patients are further randomized to 1 of 2 maintenance arms.
  • Arm I: Patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for a total of 6 courses.
  • Arm II: Patients do not receive maintenance therapy. In all arms, treatment continues in the absence of disease progression.

Patients are followed every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 80-150 patients (40-75 per treatment arm) will be accrued for this study within 5 years.

Being tested
filgrastim, carboplatin, etoposide, isotretinoin, thiotepa
Keywords
childhood high-grade cerebral astrocytoma, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma
Medical subject headings
Brain Neoplasms, Central Nervous System Neoplasms, Astrocytoma

What participants receive

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

  • filgrastimBiological

    Also called Granulocyte Colony-Stimulating Factor, r-metHuG-CSF, G-CSF, Neupogen

    Given IV

  • carboplatinDrug

    Also called Paraplain, CBDCA, NSC #241240

    Given IV

  • etoposideDrug

    Also called VP-16, VePesid, Etopophos, NSC #141540

    Given IV

  • isotretinoinDrug

    Also called 13-cis-retinoic acid, RO-43, 780, Accutane

    Given IV

  • thiotepaDrug

    Also called Tespa, Thiophosphamide, Triethylenethiophosphoramide Tspa, WR-45312

    Given IV

  • autologous bone marrow transplantationProcedure or surgery

    Also called Stem Cell Reinfusion

    Peripheral blood stem cells or bone marrow will be reinfused about 72 hours following completion of the last dose of chemotherapy (Day 0)

  • peripheral blood stem cell transplantationProcedure or surgery

    Also called Peripheral Stem Cell Collection

    Filgrastim is to be given daily in the afternoon for 4 days prior to the first harvest and continued until the completion of the daily harvests. The daily PBSC harvesting should be started prior to the fifth dose of filgrastim.

Study groups in NCT00078988
Study groupRoleWhat they receive
Arm I (high-dose chemotherapy and ASCR)ExperimentalPatients receive high-dose chemotherapy comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or SC once daily beginning on day 1 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 0.
Receives: Biological: filgrastim; Drug: carboplatin; Drug: etoposide; Drug: isotretinoin; Drug: thiotepa; Procedure: autologous bone marrow transplantation; Procedure: peripheral blood stem cell transplantation
Arm II (intermediate-dose chemotherapy and ASCR)ExperimentalPatients receive intermediate-dose chemotherapy comprising carboplatin IV over 4 hours and thiotepa IV over 3 hours on days 1-2 and G-CSF IV or SC once daily beginning on day 4 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 3. Treatment repeats every 28 days for a total of 3 courses.
Receives: Biological: filgrastim; Drug: carboplatin; Drug: thiotepa; Procedure: autologous bone marrow transplantation; Procedure: peripheral blood stem cell transplantation
Arm III (isotretinoin)ExperimentalPatients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for a total of 6 courses.
Receives: Drug: isotretinoin
Arm IV (no isotretinoin)No interventionPatients do not receive maintenance therapy.

What is being measured

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

  1. Event-free survival

    The primary endpoint for the evaluation of treatment efficacy will be event-free survival (EFS)

    Measured: om study entry to disease progression, disease relapse, occurrence of a second malignant neoplasm, or death from any cause. assessed up to 4 years

  2. Toxic death attributable to complications of treatment in the absence of tumor progression as assessed by NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0

    Toxic death will be monitored separately in each of the two chemotherapy groups

    Measured: Up to 4 years after completion of study treatment

Secondary outcomes (1)

  1. Overall survival (OS)

    Secondary endpoints include overall survival (OS), which is defined as the time from study entry to death from any cause, assessed up to 4 years

    Measured: ondary e ndpoints include overall survival (OS), which is defined as the time from study entry to death from any cause assessed up to 4 years

Timeline

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

  1. First posted9 Mar 2004 (estimated)
  2. Study startOct 2004
  3. Primary completionSep 2006
  4. Study completionSep 2006

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
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00078988
Sponsor's protocol ID
ACNS0231
Other IDs
COG-ACNS0231, CDR0000353207, NCI-2012-02578, U10CA098543
Status last verified
May 2015
First submitted
8 Mar 2004
Last updated
7 May 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing filgrastim, carboplatin and etoposide in people with Brain Tumor and Central Nervous System Tumor, run by Children's Oncology Group at 59 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?

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: finished, as of the sponsor's last update on 7 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 59 sites in United States, Canada, 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Event-free survival (time frame: om study entry to disease progression, disease relapse, occurrence of a second malignant neoplasm, or death from any cause. assessed up to 4 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 NCT00078988.

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 7 May 2015.

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