A Study of Lower Radiotherapy Dose to Treat Children With CNS Germinoma
Purpose
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.
Conditions
- Basal Ganglia Germinoma
- Central Nervous System Germinoma
- Diabetes Insipidus
- Pineal Region Germinoma
- Suprasellar Germinoma
- Thalamic Germinoma
Eligibility
- Eligible Ages
- Between 3 Years and 29 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Patients must be ≥ 3 years and < 30 years at the time of study enrollment - Patients must be newly-diagnosed primary localized germinoma of the suprasellar and/or pineal region by pathology and/or serum and/or CSF hCGbeta 5-50 mIU/mL AND institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists), including tumors with contiguous ventricular or unifocal parenchymal extension. No histologic confirmation required - Patients with EITHER (A) bifocal (pineal + suprasellar) involvement OR (B) pineal lesion with diabetes insipidus (DI) AND hCGbeta ≤ 100 mIU/mL in serum and/or CSF AND institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists) in both serum and CSF. No histologic confirmation required - Patients with hCGbeta 51-100 mIU/mL in serum and/or CSF and institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists) in both serum and CSF. Histologic confirmation of germinoma IS required - Patients with germinoma of the basal ganglia and or/thalamic primary sites are eligible - Patients with metastatic germinoma including non-contiguous disease or distant disease in the brain, ventricles, or spine are eligible - Patients with germinoma admixed with mature teratoma are eligible - Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age - Patients must have eligibility confirmed by Rapid Central Imaging Review performed on APEC14B1-CNS - Imaging studies must be obtained within 31 days prior to study enrollment and start of protocol therapy. (Note: for patients that have had surgery and post-operative imaging performed, it is the post-operative MRI that must be obtained within 31 days prior to enrollment.) - Patients must have a cranial magnetic resonance imaging (MRI) with and without gadolinium at diagnosis/prior to enrollment. If surgical resection is performed, patients must have pre-operative and post-operative brain MRI with and without gadolinium. The post-operative brain MRI should be obtained within 72 hours of surgery. If patient has a biopsy only, post-operative brain MRI is recommended but not required - Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment - Patients must be enrolled, and protocol therapy must begin, no later than 31 days after definitive surgery or clinical diagnosis, whichever is later - Patients must have eligibility confirmed by Rapid Central Tumor Marker Review performed on APEC14B1-CNS - Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be obtained at the time of surgery, then it should be performed at least 10 days following surgery and prior to study enrollment. False positive cytology can occur within 10 days of surgery. Of note, lumbar CSF should not be performed prior to obtaining spine MRI, as this can make interpretation of the spine MRI less clear - Patients must have CSF tumor markers obtained prior to study enrollment unless medically contraindicated. Ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first. Ideally serum and CSF tumor markers should be collected at the same time and processed without delay - For patients with solid tumors: Peripheral absolute neutrophil count (ANC) >= 1000/uL (Must be performed within 7 days prior to enrollment unless otherwise indicated) - For patients with solid tumors: Platelet count >= 100,000/uL (transfusion independent) (Must be performed within 7 days prior to enrollment unless otherwise indicated) - For patients with solid tumors: Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (Must be performed within 7 days prior to enrollment unless otherwise indicated) - For pediatric patients (age 3-17 years): A serum creatinine based on age/gender as follows (Must be performed within 7 days prior to enrollment unless otherwise indicated): - Age: 3 to < 6 years; maximum serum creatinine (mg/dL): 0.8 (male); 0.8 (female) - Age: 6 to < 10 years; maximum serum creatinine (mg/dL): 1 (male); 1 (female) - Age: 10 to < 13 years; maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female) - Age: 13 to < 16 years; maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female) - Age: ≥ 17 years; maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female) OR a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m^2 OR a glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard). - Note: Estimated GFR (eGFR) from serum or plasma creatinine, cystatin C or other estimates are not acceptable for determining eligibility. - For adult patients (age 18 years or older) (Must be performed within 7 days prior to enrollment unless otherwise indicated): - Creatinine clearance ≥ 70 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight - Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age (Must be performed within 7 days prior to enrollment unless otherwise indicated) - Serum glutamic-pyruvic transaminase (SGPT) (alanine transaminase [ALT]) ≤ 135 U/L (Must be performed within 7 days prior to enrollment unless otherwise indicated) - Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L - No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination - Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled - CNS toxicity =< grade 2 - Patients must not be in status epilepticus, coma or assisted ventilation prior to study enrollment - HIV-infected patients on effective anti-retroviral therapy with undetectable viral load are eligible for this study
Exclusion Criteria
- Patients with any of the following malignant pathological elements are not eligible: - Endodermal sinus (yolk sac) - Embryonal carcinoma, choriocarcinoma - Malignant/immature teratoma and mixed germ cell tumor (GCT) (i.e., may include some germinoma) - Patients with only mature teratoma upon tumor sampling at diagnosis and negative tumor markers are not eligible - Patients who have received any prior tumor-directed therapy for their diagnosis of germinoma other than surgical intervention and corticosteroids are not eligible - Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential. - Note: Serum and urine pregnancy tests may be falsely positive due to HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by institutional standards - Lactating females who plan to breastfeed their infants - Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation - All patients and/or their parents or legal guardians must sign a written informed consent - All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Stratum I (carboplatin, etoposide, 3D-CRT, IMRT, surgery) |
See Detailed Description. |
|
|
Experimental Stratum II (carboplatin, etoposide, 3D-CRT, IMRT) |
Patients receive carboplatin 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 with localized germinoma achieving PR with normalization of markers who do not undergo second-look surgery undergo 3DRT or IMRT QD 5 days a week for 20 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up. |
|
|
Experimental Stratum III (carboplatin, etoposide, 3D-CRT, IMRT) |
Patients receive carboplatin 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 with localized germinoma with normalization of markers who fail to achieve CR or PR who do not undergo second-look surgery undergo 3DRT or IMRT QD 5 days a week for 24 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up. |
|
|
Experimental Stratum IV (carboplatin, etoposide, 3D-CRT, IMRT, surgery) |
Patients receive carboplatin 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 with metastatic germinoma achieving CR undergo 3DRT or IMRT 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 3DRT or IMRT QD 5 days a week for 20 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up. |
|
|
Experimental Stratum V (carboplatin, etoposide, 3D-CRT, IMRT) |
Patients receive carboplatin 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 with metastatic germinoma with normalization of markers who fail to achieve CR who do not undergo second-look surgery undergo 3DRT or IMRT QD 5 days a week for 24 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up. |
|
|
Experimental Stratum VI (carboplatin, etoposide, 3D-CRT, IMRT, surgery) |
Patients receive carboplatin 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 with basal ganglia and thalamic germinoma achieving CR undergo 3DRT or IMRT 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 3DRT or IMRT QD 5 days a week for 20 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up. |
|
|
Experimental Stratum VII (carboplatin, etoposide, 3D-CRT, IMRT) |
Patients receive carboplatin 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 with basal ganglia and thalamic germinoma with normalization of markers who fail to achieve CR who do not undergo second-look surgery undergo 3DRT or IMRT QD 5 days a week for 24 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up. |
|
Recruiting Locations
USA Health Strada Patient Care Center
Mobile 4076598, Alabama 4829764 36604
Mobile 4076598, Alabama 4829764 36604
Contact:
Site Public Contact
800-388-8721
Site Public Contact
800-388-8721
Phoenix Childrens Hospital
Phoenix 5308655, Arizona 5551752 85016
Phoenix 5308655, Arizona 5551752 85016
Contact:
Site Public Contact
602-546-0920
Site Public Contact
602-546-0920
Arkansas Children's Hospital
Little Rock 4119403, Arkansas 4099753 72202-3591
Little Rock 4119403, Arkansas 4099753 72202-3591
Contact:
Site Public Contact
501-364-7373
Site Public Contact
501-364-7373
Loma Linda University Medical Center
Loma Linda 5367696, California 5332921 92354
Loma Linda 5367696, California 5332921 92354
Contact:
Site Public Contact
909-558-4050
Site Public Contact
909-558-4050
Children's Hospital Los Angeles
Los Angeles 5368361, California 5332921 90027
Los Angeles 5368361, California 5332921 90027
Contact:
Site Public Contact
323-361-4110
Site Public Contact
323-361-4110
UCSF Benioff Children's Hospital Oakland
Oakland 5378538, California 5332921 94609
Oakland 5378538, California 5332921 94609
Children's Hospital of Orange County
Orange 5379513, California 5332921 92868
Orange 5379513, California 5332921 92868
Lucile Packard Children's Hospital Stanford University
Palo Alto 5380748, California 5332921 94304
Palo Alto 5380748, California 5332921 94304
Rady Children's Hospital - San Diego
San Diego 5391811, California 5332921 92123
San Diego 5391811, California 5332921 92123
Contact:
Site Public Contact
858-966-5934
Site Public Contact
858-966-5934
UCSF Medical Center-Mission Bay
San Francisco 5391959, California 5332921 94158
San Francisco 5391959, California 5332921 94158
Children's Hospital Colorado
Aurora 5412347, Colorado 5417618 80045
Aurora 5412347, Colorado 5417618 80045
Connecticut Children's Medical Center
Hartford 4835797, Connecticut 4831725 06106
Hartford 4835797, Connecticut 4831725 06106
Contact:
Site Public Contact
860-545-9981
Site Public Contact
860-545-9981
Alfred I duPont Hospital for Children
Wilmington 4145381, Delaware 4142224 19803
Wilmington 4145381, Delaware 4142224 19803
Children's National Medical Center
Washington D.C. 4140963, District of Columbia 4138106 20010
Washington D.C. 4140963, District of Columbia 4138106 20010
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood 4158928, Florida 4155751 33021
Hollywood 4158928, Florida 4155751 33021
Nemours Children's Clinic-Jacksonville
Jacksonville 4160021, Florida 4155751 32207
Jacksonville 4160021, Florida 4155751 32207
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami 4164138, Florida 4155751 33136
Miami 4164138, Florida 4155751 33136
Contact:
Site Public Contact
305-243-2647
Site Public Contact
305-243-2647
Nicklaus Children's Hospital
Miami 4164138, Florida 4155751 33155
Miami 4164138, Florida 4155751 33155
Contact:
Site Public Contact
888-624-2778
Site Public Contact
888-624-2778
Arnold Palmer Hospital for Children
Orlando 4167147, Florida 4155751 32806
Orlando 4167147, Florida 4155751 32806
Nemours Children's Hospital
Orlando 4167147, Florida 4155751 32827
Orlando 4167147, Florida 4155751 32827
Nemours Children's Clinic - Pensacola
Pensacola 4168228, Florida 4155751 32504
Pensacola 4168228, Florida 4155751 32504
Johns Hopkins All Children's Hospital
St. Petersburg 4171563, Florida 4155751 33701
St. Petersburg 4171563, Florida 4155751 33701
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa 4174757, Florida 4155751 33607
Tampa 4174757, Florida 4155751 33607
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta 4180439, Georgia 4197000 30329
Atlanta 4180439, Georgia 4197000 30329
Saint Luke's Cancer Institute - Boise
Boise 5586437, Idaho 5596512 83712
Boise 5586437, Idaho 5596512 83712
Lurie Children's Hospital-Chicago
Chicago 4887398, Illinois 4896861 60611
Chicago 4887398, Illinois 4896861 60611
Contact:
Site Public Contact
773-880-4562
Site Public Contact
773-880-4562
University of Chicago Comprehensive Cancer Center
Chicago 4887398, Illinois 4896861 60637
Chicago 4887398, Illinois 4896861 60637
Loyola University Medical Center
Maywood 4901514, Illinois 4896861 60153
Maywood 4901514, Illinois 4896861 60153
Contact:
Site Public Contact
708-226-4357
Site Public Contact
708-226-4357
University of Iowa/Holden Comprehensive Cancer Center
Iowa City 4862034, Iowa 4862182 52242
Iowa City 4862034, Iowa 4862182 52242
Contact:
Site Public Contact
800-237-1225
Site Public Contact
800-237-1225
Norton Children's Hospital
Louisville 4299276, Kentucky 6254925 40202
Louisville 4299276, Kentucky 6254925 40202
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore 4347778, Maryland 4361885 21287
Baltimore 4347778, Maryland 4361885 21287
Dana-Farber Cancer Institute
Boston 4930956, Massachusetts 6254926 02215
Boston 4930956, Massachusetts 6254926 02215
Contact:
Site Public Contact
877-442-3324
Site Public Contact
877-442-3324
C S Mott Children's Hospital
Ann Arbor 4984247, Michigan 5001836 48109
Ann Arbor 4984247, Michigan 5001836 48109
Contact:
Site Public Contact
800-865-1125
Site Public Contact
800-865-1125
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids 4994358, Michigan 5001836 49503
Grand Rapids 4994358, Michigan 5001836 49503
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis 5037649, Minnesota 5037779 55404
Minneapolis 5037649, Minnesota 5037779 55404
University of Minnesota/Masonic Cancer Center
Minneapolis 5037649, Minnesota 5037779 55455
Minneapolis 5037649, Minnesota 5037779 55455
Contact:
Site Public Contact
612-624-2620
Site Public Contact
612-624-2620
Mayo Clinic in Rochester
Rochester 5043473, Minnesota 5037779 55905
Rochester 5043473, Minnesota 5037779 55905
Contact:
Site Public Contact
855-776-0015
Site Public Contact
855-776-0015
University of Mississippi Medical Center
Jackson 4431410, Mississippi 4436296 39216
Jackson 4431410, Mississippi 4436296 39216
Contact:
Site Public Contact
601-815-6700
Site Public Contact
601-815-6700
Children's Mercy Hospitals and Clinics
Kansas City 4393217, Missouri 4398678 64108
Kansas City 4393217, Missouri 4398678 64108
Cardinal Glennon Children's Medical Center
St Louis 4407066, Missouri 4398678 63104
St Louis 4407066, Missouri 4398678 63104
Contact:
Site Public Contact
314-268-4000
Site Public Contact
314-268-4000
Washington University School of Medicine
St Louis 4407066, Missouri 4398678 63110
St Louis 4407066, Missouri 4398678 63110
Children's Hospital and Medical Center of Omaha
Omaha 5074472, Nebraska 5073708 68114
Omaha 5074472, Nebraska 5073708 68114
Contact:
Site Public Contact
402-955-3949
Site Public Contact
402-955-3949
University of Nebraska Medical Center
Omaha 5074472, Nebraska 5073708 68198
Omaha 5074472, Nebraska 5073708 68198
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas 5506956, Nevada 5509151 89135
Las Vegas 5506956, Nevada 5509151 89135
Summerlin Hospital Medical Center
Las Vegas 5506956, Nevada 5509151 89144
Las Vegas 5506956, Nevada 5509151 89144
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon 5088597, New Hampshire 5090174 03756
Lebanon 5088597, New Hampshire 5090174 03756
Hackensack University Medical Center
Hackensack 5098706, New Jersey 5101760 07601
Hackensack 5098706, New Jersey 5101760 07601
Contact:
Site Public Contact
551-996-2897
Site Public Contact
551-996-2897
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick 5101717, New Jersey 5101760 08903
New Brunswick 5101717, New Jersey 5101760 08903
Contact:
Site Public Contact
732-235-8675
Site Public Contact
732-235-8675
Newark Beth Israel Medical Center
Newark 5101798, New Jersey 5101760 07112
Newark 5101798, New Jersey 5101760 07112
Saint Joseph's Regional Medical Center
Paterson 5102466, New Jersey 5101760 07503
Paterson 5102466, New Jersey 5101760 07503
Albany Medical Center
Albany 5106834, New York 5128638 12208
Albany 5106834, New York 5128638 12208
Contact:
Site Public Contact
518-262-5513
Site Public Contact
518-262-5513
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York 5128581, New York 5128638 10016
New York 5128581, New York 5128638 10016
Mount Sinai Hospital
New York 5128581, New York 5128638 10029
New York 5128581, New York 5128638 10029
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York 5128581, New York 5128638 10032
New York 5128581, New York 5128638 10032
Memorial Sloan Kettering Cancer Center
New York 5128581, New York 5128638 10065
New York 5128581, New York 5128638 10065
Contact:
Site Public Contact
212-639-7592
Site Public Contact
212-639-7592
State University of New York Upstate Medical University
Syracuse 5140405, New York 5128638 13210
Syracuse 5140405, New York 5128638 13210
Contact:
Site Public Contact
315-464-5476
Site Public Contact
315-464-5476
Montefiore Medical Center - Moses Campus
The Bronx 5110266, New York 5128638 10467
The Bronx 5110266, New York 5128638 10467
UNC Lineberger Comprehensive Cancer Center
Chapel Hill 4460162, North Carolina 4482348 27599
Chapel Hill 4460162, North Carolina 4482348 27599
Wake Forest University Health Sciences
Winston-Salem 4499612, North Carolina 4482348 27157
Winston-Salem 4499612, North Carolina 4482348 27157
Contact:
Site Public Contact
336-713-6771
Site Public Contact
336-713-6771
Sanford Broadway Medical Center
Fargo 5059163, North Dakota 5690763 58122
Fargo 5059163, North Dakota 5690763 58122
Rainbow Babies and Childrens Hospital
Cleveland 5150529, Ohio 5165418 44106
Cleveland 5150529, Ohio 5165418 44106
Contact:
Site Public Contact
216-844-5437
Site Public Contact
216-844-5437
Nationwide Children's Hospital
Columbus 4509177, Ohio 5165418 43205
Columbus 4509177, Ohio 5165418 43205
University of Oklahoma Health Sciences Center
Oklahoma City 4544349, Oklahoma 4544379 73104
Oklahoma City 4544349, Oklahoma 4544379 73104
Oregon Health and Science University
Portland 5746545, Oregon 5744337 97239
Portland 5746545, Oregon 5744337 97239
Children's Hospital of Philadelphia
Philadelphia 4560349, Pennsylvania 6254927 19104
Philadelphia 4560349, Pennsylvania 6254927 19104
Saint Christopher's Hospital for Children
Philadelphia 4560349, Pennsylvania 6254927 19134
Philadelphia 4560349, Pennsylvania 6254927 19134
Contact:
Site Public Contact
215-427-8991
Site Public Contact
215-427-8991
Children's Hospital of Pittsburgh of UPMC
Pittsburgh 5206379, Pennsylvania 6254927 15224
Pittsburgh 5206379, Pennsylvania 6254927 15224
Rhode Island Hospital
Providence 5224151, Rhode Island 5224323 02903
Providence 5224151, Rhode Island 5224323 02903
Contact:
Site Public Contact
401-444-1488
Site Public Contact
401-444-1488
Prisma Health Richland Hospital
Columbia 4575352, South Carolina 4597040 29203
Columbia 4575352, South Carolina 4597040 29203
BI-LO Charities Children's Cancer Center
Greenville 4580543, South Carolina 4597040 29605
Greenville 4580543, South Carolina 4597040 29605
Sanford USD Medical Center - Sioux Falls
Sioux Falls 5231851, South Dakota 5769223 57117-5134
Sioux Falls 5231851, South Dakota 5769223 57117-5134
Saint Jude Children's Research Hospital
Memphis 4641239, Tennessee 4662168 38105
Memphis 4641239, Tennessee 4662168 38105
Dell Children's Medical Center of Central Texas
Austin 4671654, Texas 4736286 78723
Austin 4671654, Texas 4736286 78723
Driscoll Children's Hospital
Corpus Christi 4683416, Texas 4736286 78411
Corpus Christi 4683416, Texas 4736286 78411
Medical City Dallas Hospital
Dallas 4684888, Texas 4736286 75230
Dallas 4684888, Texas 4736286 75230
Contact:
Site Public Contact
972-566-5588
Site Public Contact
972-566-5588
UT Southwestern/Simmons Cancer Center-Dallas
Dallas 4684888, Texas 4736286 75390
Dallas 4684888, Texas 4736286 75390
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston 4699066, Texas 4736286 77030
Houston 4699066, Texas 4736286 77030
M D Anderson Cancer Center
Houston 4699066, Texas 4736286 77030
Houston 4699066, Texas 4736286 77030
Children's Hospital of San Antonio
San Antonio 4726206, Texas 4736286 78207
San Antonio 4726206, Texas 4736286 78207
University of Texas Health Science Center at San Antonio
San Antonio 4726206, Texas 4736286 78229
San Antonio 4726206, Texas 4736286 78229
Primary Children's Hospital
Salt Lake City 5780993, Utah 5549030 84113
Salt Lake City 5780993, Utah 5549030 84113
Contact:
Site Public Contact
801-585-5270
Site Public Contact
801-585-5270
University of Virginia Cancer Center
Charlottesville 4752031, Virginia 6254928 22908
Charlottesville 4752031, Virginia 6254928 22908
Children's Hospital of The King's Daughters
Norfolk 4776222, Virginia 6254928 23507
Norfolk 4776222, Virginia 6254928 23507
Seattle Children's Hospital
Seattle 5809844, Washington 5815135 98105
Seattle 5809844, Washington 5815135 98105
Contact:
Site Public Contact
866-987-2000
Site Public Contact
866-987-2000
Providence Sacred Heart Medical Center and Children's Hospital
Spokane 5811696, Washington 5815135 99204
Spokane 5811696, Washington 5815135 99204
University of Wisconsin Carbone Cancer Center - University Hospital
Madison 5261457, Wisconsin 5279468 53792
Madison 5261457, Wisconsin 5279468 53792
More Details
- NCT ID
- NCT06368817
- Status
- Recruiting
- Sponsor
- Children's Oncology Group
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 (3DCRT) or intensity-modulated radiation therapy (IMRT) 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 3DRT or IMRT 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 3DRT or IMRT QD 5 days a week for 16 days. Patients with bifocal germinoma undergo 3DRT or IMRT 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 3DRT or IMRT 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 3DRT or IMRT QD 5 days a week for 24 days. STRATUM IV: Patients with metastatic germinoma achieving CR undergo 3DRT or IMRT 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 3DRT or IMRT 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 3DRT or IMRT QD 5 days a week for 24 days. STRATUM VI: Patients with basal ganglia and thalamic germinoma achieving CR undergo 3DRT or IMRT 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 3DRT or IMRT 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 3DRT or IMRT 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.