RecruitingPhase 2NCT06368817
A Study of Lower Radiotherapy Dose to Treat Children With CNS Germinoma
A Phase II Trial Evaluating Chemotherapy Followed by Response-Based Reduced Radiation Therapy for Patients With Central Nervous System Germinomas
Sponsor
Children's Oncology Group
Enrollment
240 participants
Start Date
Oct 22, 2024
Study Type
INTERVENTIONAL
Conditions
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.
Eligibility
Min Age: 3 YearsMax Age: 29 Years
Inclusion Criteria36
- 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 Criteria12
- 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
Interventions
DRUGCarboplatin
Given IV
DRUGEtoposide
Given IV
RADIATIONIntensity-Modulated Radiation Therapy
Undergo IMRT
PROCEDURELumbar Puncture
Undergo LP
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
OTHERQuestionnaire Administration
Ancillary studies
PROCEDURESurgical Procedure
Undergo second-look surgery
RADIATION3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT
PROCEDUREBiospecimen Collection
Undergo blood and CSF sample collection
Locations(106)
View Full Details on ClinicalTrials.gov
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NCT06368817