Trials Today

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 Genders: 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.	Radiation: 3-Dimensional Conformal Radiation Therapy Undergo 3D-CRT Other names: 3-dimensional radiation therapy 3D Conformal 3D CONFORMAL RADIATION THERAPY 3D CRT 3D radiotherapy 3D-CRT Conformal Therapy Radiation Conformal Therapy Radiation, 3D Conformal Three dimensional external beam radiation therapy (procedure) Procedure: Biospecimen Collection Undergo blood and CSF sample collection Other names: Biological Sample Collection Biospecimen Collected Specimen Collection Drug: Carboplatin Given IV Other names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 JM8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo Drug: Etoposide Given IV Other names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP 16213 VP-16 VP-16-213 VP-16213 VP16 VP16213 Radiation: Intensity-Modulated Radiation Therapy Undergo IMRT Other names: IMRT Intensity modulated radiation therapy (procedure) Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy Procedure: Lumbar Puncture Undergo LP Other names: LP Spinal Tap Procedure: Magnetic Resonance Imaging Undergo MRI Other names: Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Other: Questionnaire Administration Ancillary studies Procedure: Surgical Procedure Undergo second-look surgery Other names: Operation Surgery Surgery Type Surgery, NOS Surgical Surgical Intervention Surgical Interventions Surgical Procedures Type of Surgery
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.	Radiation: 3-Dimensional Conformal Radiation Therapy Undergo 3D-CRT Other names: 3-dimensional radiation therapy 3D Conformal 3D CONFORMAL RADIATION THERAPY 3D CRT 3D radiotherapy 3D-CRT Conformal Therapy Radiation Conformal Therapy Radiation, 3D Conformal Three dimensional external beam radiation therapy (procedure) Procedure: Biospecimen Collection Undergo blood and CSF sample collection Other names: Biological Sample Collection Biospecimen Collected Specimen Collection Drug: Carboplatin Given IV Other names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 JM8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo Drug: Etoposide Given IV Other names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP 16213 VP-16 VP-16-213 VP-16213 VP16 VP16213 Radiation: Intensity-Modulated Radiation Therapy Undergo IMRT Other names: IMRT Intensity modulated radiation therapy (procedure) Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy Procedure: Lumbar Puncture Undergo LP Other names: LP Spinal Tap Procedure: Magnetic Resonance Imaging Undergo MRI Other names: Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Other: Questionnaire Administration Ancillary studies
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.	Radiation: 3-Dimensional Conformal Radiation Therapy Undergo 3D-CRT Other names: 3-dimensional radiation therapy 3D Conformal 3D CONFORMAL RADIATION THERAPY 3D CRT 3D radiotherapy 3D-CRT Conformal Therapy Radiation Conformal Therapy Radiation, 3D Conformal Three dimensional external beam radiation therapy (procedure) Procedure: Biospecimen Collection Undergo blood and CSF sample collection Other names: Biological Sample Collection Biospecimen Collected Specimen Collection Drug: Carboplatin Given IV Other names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 JM8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo Drug: Etoposide Given IV Other names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP 16213 VP-16 VP-16-213 VP-16213 VP16 VP16213 Radiation: Intensity-Modulated Radiation Therapy Undergo IMRT Other names: IMRT Intensity modulated radiation therapy (procedure) Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy Procedure: Lumbar Puncture Undergo LP Other names: LP Spinal Tap Procedure: Magnetic Resonance Imaging Undergo MRI Other names: Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Other: Questionnaire Administration Ancillary studies
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.	Radiation: 3-Dimensional Conformal Radiation Therapy Undergo 3D-CRT Other names: 3-dimensional radiation therapy 3D Conformal 3D CONFORMAL RADIATION THERAPY 3D CRT 3D radiotherapy 3D-CRT Conformal Therapy Radiation Conformal Therapy Radiation, 3D Conformal Three dimensional external beam radiation therapy (procedure) Procedure: Biospecimen Collection Undergo blood and CSF sample collection Other names: Biological Sample Collection Biospecimen Collected Specimen Collection Drug: Carboplatin Given IV Other names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 JM8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo Drug: Etoposide Given IV Other names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP 16213 VP-16 VP-16-213 VP-16213 VP16 VP16213 Radiation: Intensity-Modulated Radiation Therapy Undergo IMRT Other names: IMRT Intensity modulated radiation therapy (procedure) Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy Procedure: Lumbar Puncture Undergo LP Other names: LP Spinal Tap Procedure: Magnetic Resonance Imaging Undergo MRI Other names: Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Other: Questionnaire Administration Ancillary studies Procedure: Surgical Procedure Undergo second-look surgery Other names: Operation Surgery Surgery Type Surgery, NOS Surgical Surgical Intervention Surgical Interventions Surgical Procedures Type of Surgery
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.	Radiation: 3-Dimensional Conformal Radiation Therapy Undergo 3D-CRT Other names: 3-dimensional radiation therapy 3D Conformal 3D CONFORMAL RADIATION THERAPY 3D CRT 3D radiotherapy 3D-CRT Conformal Therapy Radiation Conformal Therapy Radiation, 3D Conformal Three dimensional external beam radiation therapy (procedure) Procedure: Biospecimen Collection Undergo blood and CSF sample collection Other names: Biological Sample Collection Biospecimen Collected Specimen Collection Drug: Carboplatin Given IV Other names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 JM8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo Drug: Etoposide Given IV Other names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP 16213 VP-16 VP-16-213 VP-16213 VP16 VP16213 Radiation: Intensity-Modulated Radiation Therapy Undergo IMRT Other names: IMRT Intensity modulated radiation therapy (procedure) Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy Procedure: Lumbar Puncture Undergo LP Other names: LP Spinal Tap Procedure: Magnetic Resonance Imaging Undergo MRI Other names: Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Other: Questionnaire Administration Ancillary studies
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.	Radiation: 3-Dimensional Conformal Radiation Therapy Undergo 3D-CRT Other names: 3-dimensional radiation therapy 3D Conformal 3D CONFORMAL RADIATION THERAPY 3D CRT 3D radiotherapy 3D-CRT Conformal Therapy Radiation Conformal Therapy Radiation, 3D Conformal Three dimensional external beam radiation therapy (procedure) Procedure: Biospecimen Collection Undergo blood and CSF sample collection Other names: Biological Sample Collection Biospecimen Collected Specimen Collection Drug: Carboplatin Given IV Other names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 JM8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo Drug: Etoposide Given IV Other names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP 16213 VP-16 VP-16-213 VP-16213 VP16 VP16213 Radiation: Intensity-Modulated Radiation Therapy Undergo IMRT Other names: IMRT Intensity modulated radiation therapy (procedure) Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy Procedure: Lumbar Puncture Undergo LP Other names: LP Spinal Tap Procedure: Magnetic Resonance Imaging Undergo MRI Other names: Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Other: Questionnaire Administration Ancillary studies Procedure: Surgical Procedure Undergo second-look surgery Other names: Operation Surgery Surgery Type Surgery, NOS Surgical Surgical Intervention Surgical Interventions Surgical Procedures Type of Surgery
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.	Radiation: 3-Dimensional Conformal Radiation Therapy Undergo 3D-CRT Other names: 3-dimensional radiation therapy 3D Conformal 3D CONFORMAL RADIATION THERAPY 3D CRT 3D radiotherapy 3D-CRT Conformal Therapy Radiation Conformal Therapy Radiation, 3D Conformal Three dimensional external beam radiation therapy (procedure) Procedure: Biospecimen Collection Undergo blood and CSF sample collection Other names: Biological Sample Collection Biospecimen Collected Specimen Collection Drug: Carboplatin Given IV Other names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 JM8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo Drug: Etoposide Given IV Other names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP 16213 VP-16 VP-16-213 VP-16213 VP16 VP16213 Radiation: Intensity-Modulated Radiation Therapy Undergo IMRT Other names: IMRT Intensity modulated radiation therapy (procedure) Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy Procedure: Lumbar Puncture Undergo LP Other names: LP Spinal Tap Procedure: Magnetic Resonance Imaging Undergo MRI Other names: Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Other: Questionnaire Administration Ancillary studies

Recruiting Locations

USA Health Strada Patient Care Center
Mobile, Alabama 36604

Contact:
Site Public Contact
800-388-8721

Arkansas Children's Hospital
Little Rock, Arkansas 72202-3591

Contact:
Site Public Contact
501-364-7373

Loma Linda University Medical Center
Loma Linda, California 92354

Contact:
Site Public Contact
909-558-4050

Children's Hospital Los Angeles
Los Angeles, California 90027

Contact:
Site Public Contact
323-361-4110

Lucile Packard Children's Hospital Stanford University
Palo Alto, California 94304

Contact:
Site Public Contact
800-694-0012
ccto-office@stanford.edu

Rady Children's Hospital - San Diego
San Diego, California 92123

Contact:
Site Public Contact
858-966-5934

Children's Hospital Colorado
Aurora, Colorado 80045

Contact:
Site Public Contact
303-764-5056
josh.b.gordon@nsmtp.kp.org

Alfred I duPont Hospital for Children
Wilmington, Delaware 19803

Contact:
Site Public Contact
302-651-5572
Allison.bruce@nemours.org

Children's National Medical Center
Washington, District of Columbia 20010

Contact:
Site Public Contact
202-476-2800
OncCRC_OnCall@childrensnational.org

Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida 33021

Contact:
Site Public Contact
954-265-1847
OHR@mhs.net

Nemours Children's Clinic-Jacksonville
Jacksonville, Florida 32207

Contact:
Site Public Contact
302-651-5572
Allison.bruce@nemours.org

Nicklaus Children's Hospital
Miami, Florida 33155

Contact:
Site Public Contact
888-624-2778

Arnold Palmer Hospital for Children
Orlando, Florida 32806

Contact:
Site Public Contact
321-841-5357
Jennifer.spinelli@orlandohealth.com

Sacred Heart Hospital
Pensacola, Florida 32504

Contact:
Site Public Contact
850-416-4611
eebrou@ascension.org

Johns Hopkins All Children's Hospital
Saint Petersburg, Florida 33701

Contact:
Site Public Contact
727-767-4784
Ashley.Repp@jhmi.edu

Saint Luke's Cancer Institute - Boise
Boise, Idaho 83712

Contact:
Site Public Contact
208-381-2774
eslinget@slhs.org

Loyola University Medical Center
Maywood, Illinois 60153

Contact:
Site Public Contact
708-226-4357

University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa 52242

Contact:
Site Public Contact
800-237-1225

Norton Children's Hospital
Louisville, Kentucky 40202

Contact:
Site Public Contact
502-629-5500
CancerResource@nortonhealthcare.org

Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland 21287

Contact:
Site Public Contact
410-955-8804
jhcccro@jhmi.edu

C S Mott Children's Hospital
Ann Arbor, Michigan 48109

Contact:
Site Public Contact
800-865-1125

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan 49503

Contact:
Site Public Contact
616-267-1925
crcwm-regulatory@crcwm.org

Mayo Clinic in Rochester
Rochester, Minnesota 55905

Contact:
Site Public Contact
855-776-0015

University of Mississippi Medical Center
Jackson, Mississippi 39216

Contact:
Site Public Contact
601-815-6700

Cardinal Glennon Children's Medical Center
Saint Louis, Missouri 63104

Contact:
Site Public Contact
314-268-4000

Washington University School of Medicine
Saint Louis, Missouri 63110

Contact:
Site Public Contact
800-600-3606
info@siteman.wustl.edu

Children's Hospital and Medical Center of Omaha
Omaha, Nebraska 68114

Contact:
Site Public Contact
402-955-3949

University of Nebraska Medical Center
Omaha, Nebraska 68198

Contact:
Site Public Contact
402-559-6941
unmcrsa@unmc.edu

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire 03756

Contact:
Site Public Contact
800-639-6918
cancer.research.nurse@dartmouth.edu

Hackensack University Medical Center
Hackensack, New Jersey 07601

Contact:
Site Public Contact
551-996-2897

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey 08903

Contact:
Site Public Contact
732-235-8675

Newark Beth Israel Medical Center
Newark, New Jersey 07112

Contact:
Site Public Contact
973-926-7230
Christine.Kosmides@rwjbh.org

Saint Joseph's Regional Medical Center
Paterson, New Jersey 07503

Contact:
Site Public Contact
973-754-2207
HallL@sjhmc.org

Albany Medical Center
Albany, New York 12208

Contact:
Site Public Contact
518-262-5513

State University of New York Upstate Medical University
Syracuse, New York 13210

Contact:
Site Public Contact
315-464-5476

UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina 27599

Contact:
Site Public Contact
877-668-0683
cancerclinicaltrials@med.unc.edu

Rainbow Babies and Childrens Hospital
Cleveland, Ohio 44106

Contact:
Site Public Contact
216-844-5437

Nationwide Children's Hospital
Columbus, Ohio 43205

Contact:
Site Public Contact
614-722-6039
Melinda.Triplet@nationwidechildrens.org

Oregon Health and Science University
Portland, Oregon 97239

Contact:
Site Public Contact
503-494-1080
trials@ohsu.edu

Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104

Contact:
Site Public Contact
267-425-5544
CancerTrials@email.chop.edu

Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania 15224

Contact:
Site Public Contact
412-692-8570
jean.tersak@chp.edu

Rhode Island Hospital
Providence, Rhode Island 02903

Contact:
Site Public Contact
401-444-1488

Saint Jude Children's Research Hospital
Memphis, Tennessee 38105

Contact:
Site Public Contact
888-226-4343
referralinfo@stjude.org

Driscoll Children's Hospital
Corpus Christi, Texas 78411

Contact:
Site Public Contact
361-694-5311
Crystal.DeLosSantos@dchstx.org

Children's Hospital of San Antonio
San Antonio, Texas 78207

Contact:
Site Public Contact
210-704-2894
bridget.medina@christushealth.org

University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229

Contact:
Site Public Contact
210-450-3800
phoresearchoffice@uthscsa.edu

Primary Children's Hospital
Salt Lake City, Utah 84113

Contact:
Site Public Contact
801-585-5270

Children's Hospital of The King's Daughters
Norfolk, Virginia 23507

Contact:
Site Public Contact
757-668-7243
CCBDCresearch@chkd.org

Seattle Children's Hospital
Seattle, Washington 98105

Contact:
Site Public Contact
866-987-2000

Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington 99204

Contact:
Site Public Contact
800-228-6618
HopeBeginsHere@providence.org

University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin 53792

Contact:
Site Public Contact
800-622-8922
clinicaltrials@cancer.wisc.edu

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.