A Study of Lower Radiotherapy Dose to Treat Children With CNS Germinoma
Start Date
10/22/2024
Completion Date
11/4/2033
Summary
This phase II trial studies how well lower dose radiotherapy after chemotherapy (Carboplatin \& Etoposide) works in treating children with central nervous system (CNS) germinomas. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Researchers want to see if lowering the dose of standard radiotherapy (RT) after chemotherapy can help get rid of CNS germinomas with fewer long-term side effects.
Detailed Description
PRIMARY OBJECTIVE: I. To determine whether 12 Gy whole ventricular irradiation (WVI) and 12 Gy tumor boost would maintain similar efficacy compared to ACNS1123 stratum 2 as measured by event-free survival (EFS) in eligible patients with localized primary central nervous system (CNS) germinoma who present with serum and/or cerebrospinal fluid (CSF) human chorionic gonadotropin-beta (hCGbeta) ≤ 100 IU/L and normal alpha-fetoprotein (AFP), and meet complete response (CR) or continued complete response (CCR) criteria following chemotherapy/second-look surgery (Stratum 1). SECONDARY OBJECTIVES: I. To estimate the EFS distribution for patients with localized midline - including bifocal - CNS germinoma with partial response (PR) after chemotherapy, followed by 18 Gy WVI and 12 Gy tumor boost (Stratum 2). II. To estimate the EFS distribution for patients with localized midline - including bifocal - CNS germinoma with less than a PR after chemotherapy, followed by 24 Gy WVI and 12 Gy tumor boost (Stratum 3). III. To estimate the overall survival (OS), response rates to chemotherapy and radiotherapy (RT), as well as the patterns of failure of the various cohorts based on tumor characteristics, treatment regimen, and treatment modality. IV. To determine the impact of tumor characteristics, treatment regimen and treatment modalities on the long-term neuroendocrine function for patients with CNS germinomas. V. To prospectively evaluate processing speed of children and young adults with CNS germinoma through the Children's Oncology Group (COG) Standardized assessment battery. EXPLORATORY OBJECTIVES: I. To estimate the EFS distribution for patients with metastatic germinomas treated with chemotherapy followed by craniospinal irradiation (CSI) \[18 Gy for CR/CCR (Stratum 4)\] or \[24 Gy for less than CR (Stratum 5)\] with a 12 Gy tumor boost to the pre-treatment volume, including metastatic sites. II. To estimate the EFS distribution for patients with basal ganglia and thalamic germinomas (BGTG) treated with chemotherapy followed by whole brain irradiation (WBI) \[18 Gy for CR/CCR (Stratum 6)\] or \[24 Gy for less than CR (Stratum 7)\] with a 12 Gy tumor boost to the pre-treatment volume. III. To prospectively collect blood, cerebrospinal fluid, and tumor tissue at diagnosis and second-look surgery (if feasible) for future biology studies. IV. To prospectively measure the incidence of cerebral vascular events (stroke or transient ischemic attacks) in the follow-up period and longitudinally evaluate and model the cognitive, social and behavioral functioning of children and young adults with CNS germinoma through the COG Standardized assessment battery, and compare these outcomes based on tumor characteristics, treatment regimen, and treatment modality. OUTLINE: INDUCTION PHASE: All patients receive carboplatin intravenously (IV) over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients are then assigned to 1 of 7 strata. STRATUM I: Patients with localized germinoma achieving CR with normalization of markers undergo 3-dimensional conformal radiation therapy (3D-CRT)/3-dimensional conformal proton radiation therapy (3D-CPRT) or intensity-modulated radiation therapy (IMRT)/intensity modulated proton therapy (IMPT) once daily (QD) 5 days a week for 16 days. Patients achieving PR with normalization of markers may undergo second-look surgery. Patients found to have mature teratoma or non-viable tumor undergo 3D-CRT/3D-CPRT or IMRT/IMPT QD 5 days a week for 16 days. Patients with normalization of markers who fail to achieve CR or PR may undergo second-look surgery. Patients found to have mature teratoma or non-viable tumor undergo 3D-CRT/3D-CPRT or IMRT/IMPT QD 5 days a week for 16 days. Patients with bifocal germinoma undergo 3D-CRT/3D-CPRT or IMRT/IMPT QD 5 days a week for 16 days. STRATUM II: Patients with localized germinoma achieving PR with normalization of markers who do not undergo second-look surgery undergo 3D-CRT/3D-CPRT or IMRT/IMPT QD 5 days a week for 20 days. STRATUM III: Patients with localized germinoma with normalization of markers who fail to achieve CR or PR who do not undergo second-look surgery undergo 3D-CRT/3D-CPRT or IMRT/IMPT QD 5 days a week for 24 days. STRATUM IV: Patients with metastatic germinoma achieving CR undergo 3D-CRT/3D-CPRT or IMRT/IMPT QD 5 days a week for 20 days. Patients with metastatic germinoma and normalization of markers who fail to achieve CR may undergo second-look surgery. Patients found to have mature teratoma or non-viable tumor undergo 3D-CRT/3D-CPRT or IMRT/IMPT QD 5 days a week for 20 days. STRATUM V: Patients with metastatic germinoma with normalization of markers who fail to achieve CR who do not undergo second-look surgery undergo 3D-CRT/3D-CPRT or IMRT/IMPT QD 5 days a week for 24 days. STRATUM VI: Patients with basal ganglia and thalamic germinoma achieving CR undergo 3D-CRT/3D-CPRT or IMRT/IMPT QD 5 days a week for 20 days. Patients with basal ganglia and thalamic germinoma and normalization of markers who fail to achieve CR may undergo second-look surgery. Patients found to have mature teratoma or non-viable tumor undergo 3D-CRT/3D-CPRT or IMRT/IMPT QD 5 days a week for 20 days. STRATUM VII: Patients with basal ganglia and thalamic germinoma with normalization of markers who fail to achieve CR who do not undergo second-look surgery undergo 3D-CRT/3D-CPRT or IMRT/IMPT QD 5 days a week for 24 days. Patients with non-normalized tumor markers or PD and no second-look surgery or viable tumor during second-look surgery discontinue protocol therapy. All patients undergo magnetic resonance imaging (MRI) and optional blood and tissue sample collection throughout the study. Patients may undergo lumbar puncture (LP) for CSF sample collection during screening and follow up. After completion of study treatment, patients are followed up every 3 months for 12 months, every 4 months for 24 months, and then annually for up to 120 months.
Eligibility Criteria
Age Range: 3 years to 29 years
Interventions
3-Dimensional Conformal Proton Radiation Therapy
3-Dimensional Conformal Radiation Therapy
Biospecimen Collection
Carboplatin
Etoposide
Intensity-Modulated Proton Therapy
Intensity-Modulated Radiation Therapy
Lumbar Puncture
Magnetic Resonance Imaging
Questionnaire Administration
Surgical Procedure
Conditions
Locations
USA Health Strada Patient Care Center
Mobile, Alabama 36604
United States
Phoenix Childrens Hospital
Phoenix, Arizona 85016
United States
Arkansas Children's Hospital
Little Rock, Arkansas 72202-3591
United States
Loma Linda University Medical Center
Loma Linda, California 92354
United States
Children's Hospital Los Angeles
Los Angeles, California 90027
United States
UCSF Benioff Children's Hospital Oakland
Oakland, California 94609
United States
Children's Hospital of Orange County
Orange, California 92868
United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California 94304
United States
Rady Children's Hospital - San Diego
San Diego, California 92123
United States
UCSF Medical Center-Mission Bay
San Francisco, California 94158
United States
Children's Hospital Colorado
Aurora, Colorado 80045
United States
Connecticut Children's Medical Center
Hartford, Connecticut 06106
United States
Yale University
New Haven, Connecticut 06520
United States
Alfred I duPont Hospital for Children
Wilmington, Delaware 19803
United States
Children's National Medical Center
Washington D.C., District of Columbia 20010
United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida 33021
United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida 32207
United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida 33136
United States
Nicklaus Children's Hospital
Miami, Florida 33155
United States
Arnold Palmer Hospital for Children
Orlando, Florida 32806
United States
Nemours Children's Hospital
Orlando, Florida 32827
United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida 32504
United States
Sacred Heart Hospital
Pensacola, Florida 32504
United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida 33701
United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida 33607
United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia 30329
United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii 96826
United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho 83712
United States
Lurie Children's Hospital-Chicago
Chicago, Illinois 60611
United States
University of Illinois
Chicago, Illinois 60612
United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois 60637
United States
Loyola University Medical Center
Maywood, Illinois 60153
United States
Riley Hospital for Children
Indianapolis, Indiana 46202
United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa 52242
United States
Norton Children's Hospital
Louisville, Kentucky 40202
United States
Maine Children's Cancer Program
Scarborough, Maine 04074
United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland 21287
United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts 02114
United States
Dana-Farber Cancer Institute
Boston, Massachusetts 02215
United States
C S Mott Children's Hospital
Ann Arbor, Michigan 48109
United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan 49503
United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota 55404
United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota 55455
United States
Mayo Clinic in Rochester
Rochester, Minnesota 55905
United States
University of Mississippi Medical Center
Jackson, Mississippi 39216
United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri 64108
United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri 63104
United States
Washington University School of Medicine
St Louis, Missouri 63110
United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska 68114
United States
University of Nebraska Medical Center
Omaha, Nebraska 68198
United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada 89135
United States
Summerlin Hospital Medical Center
Las Vegas, Nevada 89144
United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire 03756
United States
Hackensack University Medical Center
Hackensack, New Jersey 07601
United States
Saint Peter's University Hospital
New Brunswick, New Jersey 08901
United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey 08903
United States
Newark Beth Israel Medical Center
Newark, New Jersey 07112
United States
Saint Joseph's Regional Medical Center
Paterson, New Jersey 07503
United States
Albany Medical Center
Albany, New York 12208
United States
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York 11040
United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York 10016
United States
Mount Sinai Hospital
New York, New York 10029
United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York 10032
United States
Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
State University of New York Upstate Medical University
Syracuse, New York 13210
United States
Montefiore Medical Center - Moses Campus
The Bronx, New York 10467
United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina 27599
United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157
United States
Sanford Broadway Medical Center
Fargo, North Dakota 58122
United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio 44106
United States
Nationwide Children's Hospital
Columbus, Ohio 43205
United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
Oregon Health and Science University
Portland, Oregon 97239
United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104
United States
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania 19134
United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania 15224
United States
Rhode Island Hospital
Providence, Rhode Island 02903
United States
Prisma Health Richland Hospital
Columbia, South Carolina 29203
United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina 29605
United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota 57117-5134
United States
Saint Jude Children's Research Hospital
Memphis, Tennessee 38105
United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee 37232
United States
Dell Children's Medical Center of Central Texas
Austin, Texas 78723
United States
Driscoll Children's Hospital
Corpus Christi, Texas 78411
United States
Medical City Dallas Hospital
Dallas, Texas 75230
United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas 75390
United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas 77030
United States
UT MD Anderson Cancer Center
Houston, Texas 77030
United States
Children's Hospital of San Antonio
San Antonio, Texas 78207
United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229
United States
Primary Children's Hospital
Salt Lake City, Utah 84113
United States
University of Virginia Cancer Center
Charlottesville, Virginia 22908
United States
Children's Hospital of The King's Daughters
Norfolk, Virginia 23507
United States
Seattle Children's Hospital
Seattle, Washington 98105
United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington 99204
United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin 53792
United States
John Hunter Children's Hospital
Hunter Regional Mail Centre, New South Wales 2310
Australia
Sydney Children's Hospital
Randwick, New South Wales 2031
Australia
The Children's Hospital at Westmead
Westmead, New South Wales 2145
Australia
Queensland Children's Hospital
South Brisbane, Queensland 4101
Australia
Women's and Children's Hospital-Adelaide
North Adelaide, South Australia 5006
Australia
Royal Children's Hospital
Parkville, Victoria 3052
Australia
Perth Children's Hospital
Perth, Western Australia 6009
Australia
University of Alberta Hospital
Edmonton, Alberta T6G 2B7
Canada
British Columbia Children's Hospital
Vancouver, British Columbia V6H 3V4
Canada
CancerCare Manitoba
Winnipeg, Manitoba R3E 0V9
Canada
IWK Health Centre
Halifax, Nova Scotia B3K 6R8
Canada
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario L8N 3Z5
Canada
Children's Hospital
London, Ontario N6A 5W9
Canada
Hospital for Sick Children
Toronto, Ontario M5G 1X8
Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec H3H 1P3
Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec H3T 1C5
Canada
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec J1H 5N4
Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2
Canada