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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00078988




Registration number
NCT00078988
Ethics application status
Date submitted
8/03/2004
Date registered
9/03/2004
Date last updated
7/05/2015

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
COG-ACNS0231
Secondary ID [2] 0 0
ACNS0231
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain Tumor 0 0
Central Nervous System Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - filgrastim
Treatment: Drugs - carboplatin
Treatment: Drugs - etoposide
Treatment: Drugs - isotretinoin
Treatment: Drugs - thiotepa
Treatment: Surgery - autologous bone marrow transplantation
Treatment: Surgery - peripheral blood stem cell transplantation

Experimental: 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 SC once daily beginning on day 1 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 0.

Experimental: 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.

Experimental: Arm III (isotretinoin) - Patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for a total of 6 courses.

No Intervention: Arm IV (no isotretinoin) - Patients do not receive maintenance therapy.


Other interventions: filgrastim
Given IV

Treatment: Drugs: carboplatin
Given IV

Treatment: Drugs: etoposide
Given IV

Treatment: Drugs: isotretinoin
Given IV

Treatment: Drugs: thiotepa
Given IV

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

Treatment: Surgery: peripheral blood stem cell transplantation
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.

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free survival - The primary endpoint for the evaluation of treatment efficacy will be event-free survival (EFS)
Timepoint [1] 0 0
om study entry to disease progression, disease relapse, occurrence of a second malignant neoplasm, or death from any cause. assessed up to 4 years
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
Up to 4 years after completion of study treatment
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
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

Eligibility
Key inclusion criteria
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
Minimum age
No limit
Maximum age
20 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

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 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
6001 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Hawaii
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Maine
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Mississippi
Country [15] 0 0
United States of America
State/province [15] 0 0
Missouri
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New York
Country [18] 0 0
United States of America
State/province [18] 0 0
Ohio
Country [19] 0 0
United States of America
State/province [19] 0 0
Oklahoma
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
State/province [21] 0 0
South Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
South Dakota
Country [23] 0 0
United States of America
State/province [23] 0 0
Texas
Country [24] 0 0
United States of America
State/province [24] 0 0
Utah
Country [25] 0 0
United States of America
State/province [25] 0 0
Virginia
Country [26] 0 0
United States of America
State/province [26] 0 0
Wisconsin
Country [27] 0 0
Canada
State/province [27] 0 0
British Columbia
Country [28] 0 0
Canada
State/province [28] 0 0
Ontario
Country [29] 0 0
Canada
State/province [29] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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 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.
Trial website
https://clinicaltrials.gov/show/NCT00078988
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ziad Khatib, MD
Address 0 0
Nicklaus Children's Hospital f/k/a Miami 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

Summary results
Other publications