Radiation Therapy, Temozolomide, and Lomustine in Treating Young Patients With Newly Diagnosed Gliomas

Condition(s) targeted: Brain and Central Nervous System Tumors

Intervention: lomustine (Drug); temozolomide (Drug); adjuvant therapy (Procedure); radiation therapy (Procedure)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Children's Oncology Group

Official(s) and/or principal investigator(s):
Regina Jakacki, MD, Study Chair, Affiliation: Children's Hospital of Pittsburgh

RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with temozolomide and lomustine after surgery may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well giving radiation therapy together with temozolomide and lomustine works in treating young patients with newly diagnosed gliomas.

Official title: A Phase II Study of Concurrent Radiation and Temozolomide Followed By Temozolomide and CCNU in the Treatment of Children With High-Grade Glioma

Study design: Treatment

Primary outcome:

Event-free survival

Toxicity

Correlation of MGMT and p53 expression in tumor tissue with outcome

Correlation of polymorphisms in GSTP1, GSTM1, and GSTT1 genes and GSTP1 protein expression in tumors with survival

Detailed description: OBJECTIVES:

- Compare event-free survival of pediatric patients with newly diagnosed high-grade

gliomas treated with adjuvant radiotherapy and temozolomide followed by temozolomide and lomustine with historical controls.

- Determine the toxicity of this regimen in these patients.

- Correlate MGMT and p53 expression in tumor tissue with outcome in patients treated with

this regimen.

- Correlate polymorphisms in GSTP1, GSTM1, and GSTT1 genes and GSTP1 protein expression in

tumors with survival in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

- Chemoradiotherapy: Patients receive oral temozolomide once daily on days 1-42. Patients

also undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients who did not undergo prior gross total resection also undergo boost radiotherapy once daily on days 43-47.

- Maintenance chemotherapy: Four weeks after completion of chemoradiotherapy, patients

receive oral temozolomide once daily on days 1-5 and oral lomustine on day 1. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 50-100 patients will be accrued for this study within 1-1. 5 years.

Minimum age: 3 Years. Maximum age: 21 Years. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically confirmed, newly diagnosed high-grade glioma of 1 of the following

histologies:

- Anaplastic astrocytoma

- Glioblastoma multiforme

- Gliosarcoma

- Primary spinal cord malignant gliomas allowed

- No primary brainstem tumors

- Has undergone surgical resection or biopsy of the tumor within the past 31 days

- Pre-operative and post-operative brain MRI with and without gadolinium-contrast

OR pre-operative and post-operative spine MRI for spinal cord primaries

- Post-operative MRI not required for patients who undergo biopsy only

- No evidence of neuraxis dissemination

- Spine MRI and cerebrospinal fluid cytology required only if clinically indicated

PATIENT CHARACTERISTICS:

Age

- 3 to 21

Performance status

- Karnofsky 50-100% (for patients > 16 years of age)

- Lansky 50-100% (for patients ≤ 16 years of age)

Life expectancy

- At least 8 weeks

Hematopoietic

- Absolute neutrophil count ≥ 1,000/mm^3

- Platelet count ≥ 100,000/mm^3 (transfusion independent)

- Hemoglobin ≥ 8 g/dL (transfusions allowed)

Hepatic

- Bilirubin ≤ 1. 5 times upper limit of normal (ULN)

- ALT ≤ 2. 5 times ULN

- Albumin ≥ 2 g/dL

Renal

- Creatinine ≤ 1. 5 times ULN OR

- Creatinine clearance or radioisotope glomerular filtration rate ≥ lower limit of

normal

Pulmonary

- No evidence of dyspnea at rest

- No exercise intolerance

- Pulse oximetry ≥ 94% (if determination is clinically indicated)

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 2 months after study

participation

- Able to swallow oral medication

- Seizures allowed provided they are well controlled with anticonvulsants

- No hypersensitivity to temozolomide

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior biologic agents

Chemotherapy

- No prior chemotherapy

Endocrine therapy

- Prior corticosteroids allowed

- No concurrent corticosteroids as an antiemetic

- Concurrent corticosteroids allowed only for treatment of increased intracranial

pressure

Radiotherapy

- No concurrent radiotherapy using cobalt-60

Surgery

- See Disease Characteristics

Other

- No other prior treatment

- No concurrent phenobarbital or cimetidine

- No concurrent co-trimoxazole for Pneumocystis carinii pneumonia prophylaxis during

study chemoradiotherapy

Centre Hospitalier Universitaire de Quebec, Quebec G1V 4G2, Canada

Christchurch Hospital, Christchurch, New Zealand

Starship Children's Health, Auckland 1, New Zealand

Wellington Children's Hospital, Wellington 6002, New Zealand

San Jorge Children's Hospital, Santurce 00912, Puerto Rico

Swiss Pediatric Oncology Group Geneva, Geneva 1205, Switzerland

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham, Birmingham, Alabama 35294, United States

CHUS-Hopital Fleurimont, Sherbrooke, Alberta J1H5N4, Canada

Phoenix Children's Hospital, Phoenix, Arizona 85016-7710, United States

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 & Research Center Oakland, Oakland, California 94609-1809, United States

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

Childrens Hospital Los Angeles, Los Angeles, California 90027, United States

Children's Hospital of Orange County, Orange, California 92868, United States

Jonathan Jaques Children's Cancer Center at Miller Children's Hospital, Long Beach, California 90801, United States

Kaiser Permanente Medical Center - Oakland, Sacramento, California 95825, United States

Loma Linda University Cancer Institute at Loma Linda University Medical Center, Loma Linda, California 92354, United States

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles, California 90048-1865, United States

Southern California Permanente Medical Group, Downey, California 90242-2814, United States

Stanford Comprehensive Cancer Center - Stanford, Stanford, California 94305, United States

Sutter Cancer Center, Sacramento, California 95816, United States

UCSF Comprehensive Cancer Center, San Francisco, California 94115, United States

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

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

Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center, Farmington, Connecticut 06360-2875, United States

Alfred I. duPont Hospital for Children, Wilmington, Delaware 19899, United States

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

Broward General Medical Center Cancer Center, Ft. Lauderdale, Florida 33316, United States

Florida Hospital Cancer Institute at Florida Hospital Orlando, Orlando, Florida 32803-1273, United States

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

Lee Cancer Care of Lee Memorial Health System, Fort Myers, Florida 33901, United States

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

Sacred Heart Cancer Center at Sacred Heart Hospital, Pensacola, Florida 32504, United States

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

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

MBCCOP - Medical College of Georgia Cancer Center, Augusta, Georgia 30912-3730, United States

Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, United States

Advocate Christ Medical Center, Oak Lawn, Illinois 60453, United States

Advocate Lutheran General Cancer Care Center, Park Ridge, Illinois 60068-1174, United States

Children's Memorial Hospital - Chicago, Chicago, Illinois 60614, United States

Saint Jude Midwest Affiliate, Peoria, Illinois 61637, United States

Southern Illinois University School of Medicine, Springfield, Illinois 62794-9620, United States

University of Chicago Cancer Research Center, Chicago, Illinois 60637-1470, United States

Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202-5289, United States

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

Blank Children's Hospital, Des Moines, Iowa 50309, United States

Holden Comprehensive Cancer Center at University of Iowa, Iowa City, Iowa 52242-1002, United States

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City, Kansas 66160-7357, United States

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

Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0293, United States

Ochsner Cancer Institute at Ochsner Clinic Foundation, New Orleans, Louisiana 70121, United States

Tulane Cancer Center Office of Clinical Research, Alexandria, Louisiana 71315-3198, United States

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

Maine Children's Cancer Program at Barbara Bush Children's Hospital, Scarborough, Maine 04074-9308, United States

CancerCare Manitoba, Winnipeg, Manitoba R3E 0V9, Canada

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States

Massachusetts General Hospital, Boston, Massachusetts 02114, United States

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

Breslin Cancer Center at Ingham Regional Medical Center, Lansing, Michigan 48910, United States

Hurley Medical Center, Flint, Michigan 48503, United States

Spectrum Health Hospital - 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 Hospitals and Clinics of Minnesota - Minneapolis, Minneapolis, Minnesota 55404, United States

Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States

University of Minnesota Children's Hospital - Fairview, Minneapolis, Minnesota 55455, United States

University of Mississippi Cancer Clinic, Jackson, Mississippi 39216-4505, United States

Cardinal Glennon Children's Hospital, St. Louis, Missouri 63104, United States

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

Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia, Missouri 65203, United States

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

Children's Hospital, Omaha, Nebraska 68114-4113, United States

Sunrise Hospital and Medical Center, Las Vegas, Nevada 89109-2306, United States

Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center, Lebanon, New Hampshire 03756-0002, United States

Hackensack University Medical Center Cancer Center, Hackensack, New Jersey 07601, United States

Overlook Hospital, Morristown, New Jersey 07962, United States

Saint Peter's University Hospital, New Brunswick, New Jersey 08901, United States

St. Joseph's Hospital and Medical Center, Paterson, New Jersey 07503, United States

University of New Mexico Cancer Research and Treatment Center, Albuquerque, New Mexico 87131-5636, United States

John Hunter Hospital, Newcastle, New South Wales 2310, Australia

Westmead Institute for Cancer Research at Westmead Hospital, Westmead, New South Wales 2145, Australia

Albany Medical Center Hospital, Albany, New York 12208-3419, United States

Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx, New York 10461, United States

Brooklyn Hospital Center, Brooklyn, New York 11201-5493, United States

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

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

Memorial Sloan - Kettering Cancer Center, New York, New York 10021-6094, United States

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

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

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

Schneider Children's Hospital, New Hyde Park, New York 11040, United States

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

Winthrop University Hospital, Mineola, New York 11501, United States

Blumenthal Cancer Center at Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill, North Carolina 27599-7295, United States

Presbyterian Cancer Center at Presbyterian Hospital, Charlotte, North Carolina 28233-3549, United States

Wake Forest University Comprehensive Cancer Center, Winston-Salem, North Carolina 27157-1096, United States

CCOP - MeritCare Hospital, Fargo, North Dakota 58122, United States

IWK Health Centre, Halifax, Nova Scotia B3K 6R8, Canada

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

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

Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195-5217, United States

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

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

Tod Children's Hospital, Youngstown, Ohio 44501, United States

Toledo Hospital, Toledo, Ohio 43606, United States

Oklahoma University Cancer Institute, Oklahoma City, Oklahoma 73104, United States

Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, Ontario K7L 3N6, Canada

Children's Hospital of Western Ontario, London, Ontario N6A 4G5, Canada

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

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

Legacy Emanuel Hospital and Health Center & Children's Hospital, Portland, Oregon 97227, United States

Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States

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

St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134-1095, United States

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

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

Royal Children's Hospital, Herston, Brisbane, Queensland 4029, Australia

Rhode Island Hospital Comprehensive Cancer Center, Providence, Rhode Island 02903, United States

Saskatoon Cancer Centre at the University of Saskatchewan, Saskatoon, Saskatchewan S7N 4H4, Canada

Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia

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

Palmetto Health South Carolina Cancer Center, Columbia, South Carolina 29203, United States

Sanford Cancer Center at Sanford USD Medical Center, Sioux Falls, South Dakota 57117-5039, United States

East Tennessee Children's Hospital, Knoxville, Tennessee 37901, United States

St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States

Baylor University Medical Center - Houston, Houston, Texas 77030-2399, United States

CCOP - Scott and White Hospital, Temple, Texas 76508, United States

Children's Hospital of Austin, Austin, Texas 78701, United States

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

Driscoll Children's Hospital, Corpus Christi, Texas 78411, United States

Medical City Dallas Hospital, Dallas, Texas 75230, United States

Methodist Children's Hospital of South Texas, San Antonio, Texas 78229-3993, United States

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas, Texas 75390, United States

Texas Tech University Health Sciences Center School of Medicine - Amarillo, Amarillo, Texas 79106, United States

University of Texas Health Science Center at San Antonio, San Antonio, Texas 78207, United States

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

Fletcher Allen Health Care - University Health Center Campus, Burlington, Vermont 05405, United States

Carilion Cancer Center of Western Virginia, Roanoke, Virginia 24029, United States

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

INOVA Fairfax Hospital, Fairfax, Virginia 22031, United States

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

Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States

Madigan Army Medical Center - Tacoma, Tacoma, Washington 98431, United States

Providence Cancer Center at Sacred Heart Medical Center, Spokane, Washington 99220-2555, United States

Edwards Comprehensive Cancer Center at Cabell Huntington Hospital, Huntington, West Virginia 25701, United States

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

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

Midwest Children's Cancer Center, Milwaukee, Wisconsin 53226, United States

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

Starting date: March 2005
Last updated: May 23, 2008