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

NCT00078988 | Completed Phase 3 DMC

• 5 other identifiers: ACNS0231COG-ACNS0231CDR0000353207NCI-2012-02578U10CA098543
• Study Type: interventional
• Target: 1
• Locations: 3 countries
• Sites: 59

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.

Conditions

Brain Tumor; Central Nervous System Tumor

Keywords

childhood high-grade cerebral astrocytoma; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma

Outcome Measures

Primary Outcomes (2)

• Event-free survival

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

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

• 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

  Up to 4 years after completion of study treatment

Secondary Outcomes (1)

• Overall survival (OS)

  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

Study Arms (4)

Arm I (high-dose chemotherapy and ASCR)

EXPERIMENTAL

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.

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)

EXPERIMENTAL

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.

Biological: filgrastim; Drug: carboplatin; Drug: thiotepa; Procedure: autologous bone marrow transplantation; Procedure: peripheral blood stem cell transplantation

Arm III (isotretinoin)

EXPERIMENTAL

Patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for a total of 6 courses.

Drug: isotretinoin

Arm IV (no isotretinoin)

NO INTERVENTION

Patients do not receive maintenance therapy.

Interventions

filgrastim BIOLOGICAL

Given IV

Also known as: Granulocyte Colony-Stimulating Factor, r-metHuG-CSF, G-CSF, Neupogen, NSC 614629

Arm I (high-dose chemotherapy and ASCR); Arm II (intermediate-dose chemotherapy and ASCR)

carboplatin DRUG

Given IV

Also known as: Paraplain, CBDCA, NSC #241240

Arm I (high-dose chemotherapy and ASCR); Arm II (intermediate-dose chemotherapy and ASCR)

etoposide DRUG

Given IV

Also known as: VP-16, VePesid, Etopophos, NSC #141540

Arm I (high-dose chemotherapy and ASCR)

isotretinoin DRUG

Given IV

Also known as: 13-cis-retinoic acid, RO-43, 780, Accutane, NSC#329481

Arm I (high-dose chemotherapy and ASCR); Arm III (isotretinoin)

thiotepa DRUG

Given IV

Also known as: Tespa, Thiophosphamide, Triethylenethiophosphoramide Tspa, WR-45312, NSC#6396

Arm I (high-dose chemotherapy and ASCR); Arm II (intermediate-dose chemotherapy and ASCR)

autologous bone marrow transplantation PROCEDURE

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

Also known as: Stem Cell Reinfusion

Arm I (high-dose chemotherapy and ASCR); Arm II (intermediate-dose chemotherapy and ASCR)

peripheral blood stem cell transplantation PROCEDURE

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.

Also known as: Peripheral Stem Cell Collection

Arm I (high-dose chemotherapy and ASCR); Arm II (intermediate-dose chemotherapy and ASCR)

Eligibility Criteria

• Age: Up to 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (59)

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Children's Hospital and Research Center - Oakland

Oakland, California, 94609-1809, United States

Location

University of California Davis Cancer Center

Sacramento, California, 95817, United States

Location

Children's Hospital and Health Center - San Diego

San Diego, California, 92123-4282, United States

Location

Children's Hospital Cancer Center

Denver, Colorado, 80218-1088, United States

Location

Children's National Medical Center

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

Location

University of Florida Shands Cancer Center

Gainesville, Florida, 32610-0232, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Miami Children's Hospital

Miami, Florida, 33155, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

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

Tampa, Florida, 33607, United States

Location

Kaplan Cancer Center at St. Mary's Medical Center

West Palm Beach, Florida, 33407, United States

Location

Emory University Hospital - Atlanta

Atlanta, Georgia, 30322, United States

Location

Cancer Research Center of Hawaii

Honolulu, Hawaii, 95813, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

St. Vincent Indianapolis Hospital

Indianapolis, Indiana, 46260, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40232, United States

Location

CancerCare of Maine at Eastern Maine Medial Center

Bangor, Maine, 04401, United States

Location

Floating Hospital for Children at Tufts - New England Medical Center

Boston, Massachusetts, 02111, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Spectrum Health Cancer Care - Butterworth Campus

Grand Rapids, Michigan, 49503-2560, United States

Location

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

Grosse Pointe Woods, Michigan, 48236, United States

Location

Children's Hospital of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

Fairview University Medical Center - University Campus

Minneapolis, Minnesota, 55455, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216-4505, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

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

New Brunswick, New Jersey, 08903, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

NYU Cancer Institute at New York University Medical Center

New York, New York, 10016, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University

New York, New York, 10032, United States

Location

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

Rochester, New York, 14642, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308-1062, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106-5000, United States

Location

Columbus Children's Hospital

Columbus, Ohio, 43205-2696, United States

Location

Children's Medical Center - Dayton

Dayton, Ohio, 45404-1815, United States

Location

Oklahoma University Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Sioux Valley Hospital and University of South Dakota Medical Center

Sioux Falls, South Dakota, 57117-5039, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104-9958, United States

Location

Covenant Children's Hospital

Lubbock, Texas, 79410, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84113-1100, United States

Location

INOVA Fairfax Hospital

Fairfax, Virginia, 22031, United States

Location

Children's Hospital of the King's Daughters

Norfolk, Virginia, 23507-1971, United States

Location

Massey Cancer Center at Virginia Commonwealth University

Richmond, Virginia, 23298-0037, United States

Location

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, 54449, United States

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

Children's & Women's Hospital of British Columbia

Vancouver, British Columbia, V6H 3V4, Canada

Location

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, H3H 1P3, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Centre Hospitalier Universitaire de Quebec

Ste-Foy, Quebec, G1V 4G2, Canada

Location

MeSH Terms

Conditions

Brain Neoplasms; Central Nervous System Neoplasms; Astrocytoma

Interventions

Filgrastim; Granulocyte Colony-Stimulating Factor; Carboplatin; Etoposide; etoposide phosphate; Isotretinoin; Thiotepa; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Terpenes; Pigments, Biological; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Ziad Khatib, MD

  Nicklaus Children's Hospital f/k/a Miami Children's Hospital

  STUDY CHAIR

• Sharon L. Gardner, MD

  NYU Langone Health

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2004
• First Posted: March 9, 2004
• Study Start: October 1, 2004
• Primary Completion: September 1, 2006
• Study Completion: September 1, 2006
• Last Updated: May 7, 2015

Record last verified: 2015-05

Locations

CA (6); US (52); AU (1)