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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

Information source: Children's Oncology Group
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Brain Tumor; Central Nervous System Tumor

Intervention: filgrastim (Biological); carboplatin (Drug); etoposide (Drug); isotretinoin (Drug); thiotepa (Drug); autologous bone marrow transplantation (Procedure); peripheral blood stem cell transplantation (Procedure)

Phase: Phase 3

Status: Completed

Sponsored by: Children's Oncology Group

Official(s) and/or principal investigator(s):
Ziad Khatib, MD, Study Chair, Affiliation: Miami Children's Hospital
Sharon L. Gardner, MD, Study Chair, Affiliation: New York University School of Medicine

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.

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Event-free survival

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

Secondary outcome: Overall survival (OS)

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.

Eligibility

Minimum age: N/A. Maximum age: 20 Years. Gender(s): Both.

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

Locations and Contacts

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States

Children's & Women's Hospital of British Columbia, Vancouver, British Columbia V6H 3V4, Canada

Children's Hospital and Research Center - Oakland, Oakland, California 94609-1809, United States

University of California Davis Cancer Center, Sacramento, California 95817, United States

Children's Hospital and Health Center - San Diego, San Diego, California 92123-4282, United States

Children's Hospital Cancer Center, Denver, Colorado 80218-1088, United States

Children's National Medical Center, Washington, District of Columbia 20010-2970, United States

University of Florida Shands Cancer Center, Gainesville, Florida 32610-0232, United States

Nemours Children's Clinic, Jacksonville, Florida 32207, United States

Miami Children's Hospital, Miami, Florida 33155, United States

University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida 33136, United States

All Children's Hospital, St. Petersburg, Florida 33701, United States

St. Joseph's Cancer Institute at St. Joseph's Hospital, Tampa, Florida 33607, United States

Kaplan Cancer Center at St. Mary's Medical Center, West Palm Beach, Florida 33407, United States

Emory University Hospital - Atlanta, Atlanta, Georgia 30322, United States

Cancer Research Center of Hawaii, Honolulu, Hawaii 95813, United States

Indiana University Cancer Center, Indianapolis, Indiana 46202-5289, United States

St. Vincent Indianapolis Hospital, Indianapolis, Indiana 46260, United States

Kosair Children's Hospital, Louisville, Kentucky 40232, United States

CancerCare of Maine at Eastern Maine Medial Center, Bangor, Maine 04401, United States

Floating Hospital for Children at Tufts - New England Medical Center, Boston, Massachusetts 02111, United States

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States

Spectrum Health Cancer Care - Butterworth Campus, Grand Rapids, Michigan 49503-2560, United States

Van Elslander Cancer Center at St. John Hospital and Medical Center, Grosse Pointe Woods, Michigan 48236, United States

Children's Hospital of Minnesota - Minneapolis, Minneapolis, Minnesota 55404, United States

Fairview University Medical Center - University Campus, Minneapolis, Minnesota 55455, United States

University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States

Children's Mercy Hospital, Kansas City, Missouri 64108, United States

Siteman Cancer Center at Barnes-Jewish Hospital, St. Louis, Missouri 63110, United States

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, United States

Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States

Herbert Irving Comprehensive Cancer Center at Columbia University, New York, New York 10032, United States

NYU Cancer Institute at New York University Medical Center, New York, New York 10016, United States

James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester, New York 14642, United States

SUNY Upstate Medical University Hospital, Syracuse, New York 13210, United States

New York Medical College, Valhalla, New York 10595, United States

Children's Hospital Medical Center of Akron, Akron, Ohio 44308-1062, United States

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, United States

Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106-5000, United States

Columbus Children's Hospital, Columbus, Ohio 43205-2696, United States

Children's Medical Center - Dayton, Dayton, Ohio 45404-1815, United States

Oklahoma University Medical Center, Oklahoma City, Oklahoma 73104, United States

McMaster Children's Hospital at Hamilton Health Sciences, Hamilton, Ontario L8N 3Z5, Canada

Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada

Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, United States

Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada

Montreal Children's Hospital at McGill University Health Center, Montreal, Quebec H3H 1P3, Canada

Centre Hospitalier Universitaire de Quebec, Ste-Foy, Quebec G1V 4G2, Canada

Hollings Cancer Center at Medical University of South Carolina, Charleston, South Carolina 29425, United States

Sioux Valley Hospital and University of South Dakota Medical Center, Sioux Falls, South Dakota 57117-5039, United States

Cook Children's Medical Center - Fort Worth, Fort Worth, Texas 76104-9958, United States

Covenant Children's Hospital, Lubbock, Texas 79410, United States

Primary Children's Medical Center, Salt Lake City, Utah 84113-1100, United States

INOVA Fairfax Hospital, Fairfax, Virginia 22031, United States

Children's Hospital of the King's Daughters, Norfolk, Virginia 23507-1971, United States

Massey Cancer Center at Virginia Commonwealth University, Richmond, Virginia 23298-0037, United States

Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia

University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53792-6164, United States

Marshfield Clinic - Marshfield Center, Marshfield, Wisconsin 54449, United States

Additional Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: October 2004
Last updated: May 6, 2015

Page last updated: August 23, 2015

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