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A Study of Lower Radiotherapy Dose to Treat Children With CNS Germinoma

RecruitingPhase 2

A Phase II Trial Evaluating Chemotherapy Followed by Response-Based Reduced Radiation Therapy for Patients With Central Nervous System Germinomas

Who can join

Ages 3 to 29 · All sexes

Full eligibility criteria
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/sex 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

About the study

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.

What is being tested

Sponsor: Children's Oncology Group · Participants: 240 · Started: Oct 22, 2024

Contact the study team

Official record on ClinicalTrials.gov — NCT06368817

Locations in the U.S.

AlabamaUSA Health Strada Patient Care Center, Mobile
ArizonaPhoenix Childrens Hospital, Phoenix
ArkansasArkansas Children's Hospital, Little Rock
CaliforniaLoma Linda University Medical Center, Loma Linda
Children's Hospital Los Angeles, Los Angeles
UCSF Benioff Children's Hospital Oakland, Oakland
Children's Hospital of Orange County, Orange
Lucile Packard Children's Hospital Stanford University, Palo Alto
Rady Children's Hospital - San Diego, San Diego
UCSF Medical Center-Mission Bay, San Francisco
ColoradoChildren's Hospital Colorado, Aurora
ConnecticutConnecticut Children's Medical Center, Hartford
Yale University, New Haven
DelawareAlfred I duPont Hospital for Children, Wilmington
District of ColumbiaChildren's National Medical Center, Washington D.C.
FloridaMemorial Regional Hospital/Joe DiMaggio Children's Hospital, Hollywood
Nemours Children's Clinic-Jacksonville, Jacksonville
Nicklaus Children's Hospital, Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center, Miami
Arnold Palmer Hospital for Children, Orlando
Nemours Children's Hospital, Orlando
Nemours Children's Clinic - Pensacola, Pensacola
Johns Hopkins All Children's Hospital, St. Petersburg
Saint Joseph's Hospital/Children's Hospital-Tampa, Tampa
GeorgiaChildren's Healthcare of Atlanta - Arthur M Blank Hospital, Atlanta
HawaiiKapiolani Medical Center for Women and Children, Honolulu
IdahoSaint Luke's Cancer Institute - Boise, Boise
IllinoisLurie Children's Hospital-Chicago, Chicago
University of Chicago Comprehensive Cancer Center, Chicago
University of Illinois, Chicago
Loyola University Medical Center, Maywood
IndianaRiley Hospital for Children, Indianapolis
IowaUniversity of Iowa/Holden Comprehensive Cancer Center, Iowa City
KentuckyNorton Children's Hospital, Louisville
MaineMaine Children's Cancer Program, Scarborough
MarylandJohns Hopkins University/Sidney Kimmel Cancer Center, Baltimore
MassachusettsDana-Farber Cancer Institute, Boston
MichiganC S Mott Children's Hospital, Ann Arbor
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital, Grand Rapids
MinnesotaChildren's Hospitals and Clinics of Minnesota - Minneapolis, Minneapolis
University of Minnesota/Masonic Cancer Center, Minneapolis
Mayo Clinic in Rochester, Rochester
MississippiUniversity of Mississippi Medical Center, Jackson
MissouriChildren's Mercy Hospitals and Clinics, Kansas City
Cardinal Glennon Children's Medical Center, St Louis
Washington University School of Medicine, St Louis
NebraskaChildren's Hospital and Medical Center of Omaha, Omaha
University of Nebraska Medical Center, Omaha
NevadaAlliance for Childhood Diseases/Cure 4 the Kids Foundation, Las Vegas
Summerlin Hospital Medical Center, Las Vegas
New HampshireDartmouth Hitchcock Medical Center/Dartmouth Cancer Center, Lebanon
New JerseyHackensack University Medical Center, Hackensack
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital, New Brunswick
Saint Peter's University Hospital, New Brunswick
Newark Beth Israel Medical Center, Newark
Saint Joseph's Regional Medical Center, Paterson
New YorkAlbany Medical Center, Albany
The Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park
Laura and Isaac Perlmutter Cancer Center at NYU Langone, New York
Memorial Sloan Kettering Cancer Center, New York
Mount Sinai Hospital, New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center, New York
State University of New York Upstate Medical University, Syracuse
Montefiore Medical Center - Moses Campus, The Bronx
North CarolinaUNC Lineberger Comprehensive Cancer Center, Chapel Hill
Wake Forest University Health Sciences, Winston-Salem
North DakotaSanford Broadway Medical Center, Fargo
OhioRainbow Babies and Childrens Hospital, Cleveland
Nationwide Children's Hospital, Columbus
OklahomaUniversity of Oklahoma Health Sciences Center, Oklahoma City
OregonOregon Health and Science University, Portland
PennsylvaniaChildren's Hospital of Philadelphia, Philadelphia
Saint Christopher's Hospital for Children, Philadelphia
Children's Hospital of Pittsburgh of UPMC, Pittsburgh
Rhode IslandRhode Island Hospital, Providence
South CarolinaPrisma Health Richland Hospital, Columbia
BI-LO Charities Children's Cancer Center, Greenville
South DakotaSanford USD Medical Center - Sioux Falls, Sioux Falls
TennesseeEast Tennessee Childrens Hospital, Knoxville
Saint Jude Children's Research Hospital, Memphis
Vanderbilt University/Ingram Cancer Center, Nashville
TexasDell Children's Medical Center of Central Texas, Austin
Driscoll Children's Hospital, Corpus Christi
Medical City Dallas Hospital, Dallas
UT Southwestern/Simmons Cancer Center-Dallas, Dallas
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center, Houston
UT MD Anderson Cancer Center, Houston
Children's Hospital of San Antonio, San Antonio
University of Texas Health Science Center at San Antonio, San Antonio
UtahPrimary Children's Hospital, Salt Lake City
VirginiaUniversity of Virginia Cancer Center, Charlottesville
Children's Hospital of The King's Daughters, Norfolk
WashingtonSeattle Children's Hospital, Seattle
Providence Sacred Heart Medical Center and Children's Hospital, Spokane
WisconsinUniversity of Wisconsin Carbone Cancer Center - University Hospital, Madison

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.