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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06368817




Registration number
NCT06368817
Ethics application status
Date submitted
8/04/2024
Date registered
16/04/2024
Date last updated
25/03/2025

Titles & IDs
Public title
A Study of Lower Radiotherapy Dose to Treat Children With CNS Germinoma
Scientific title
A Phase II Trial Evaluating Chemotherapy Followed by Response-Based Reduced Radiation Therapy for Patients With Central Nervous System Germinomas
Secondary ID [1] 0 0
NCI-2024-03518
Secondary ID [2] 0 0
ACNS2321
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Basal Ganglia Germinoma 0 0
Central Nervous System Germinoma 0 0
Diabetes Insipidus 0 0
Pineal Region Germinoma 0 0
Suprasellar Germinoma 0 0
Thalamic Germinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types
Metabolic and Endocrine 0 0 0 0
Diabetes
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - 3-Dimensional Conformal Radiation Therapy
Treatment: Surgery - Biospecimen Collection
Treatment: Drugs - Carboplatin
Treatment: Drugs - Etoposide
Treatment: Other - Intensity-Modulated Radiation Therapy
Treatment: Surgery - Lumbar Puncture
Treatment: Surgery - Magnetic Resonance Imaging
Other interventions - Questionnaire Administration
Treatment: Surgery - Surgical Procedure

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.


Treatment: Other: 3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT

Treatment: Surgery: Biospecimen Collection
Undergo blood and CSF sample collection

Treatment: Drugs: Carboplatin
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Other: Intensity-Modulated Radiation Therapy
Undergo IMRT

Treatment: Surgery: Lumbar Puncture
Undergo LP

Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI

Other interventions: Questionnaire Administration
Ancillary studies

Treatment: Surgery: Surgical Procedure
Undergo second-look surgery
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Surgery
Intervention code [3] 0 0
Treatment: Drugs
Intervention code [4] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free survival (EFS) (Stratum I)
Timepoint [1] 0 0
Evaluated at 2- and 3-years post-radiation initiation
Secondary outcome [1] 0 0
EFS (Stratum II)
Timepoint [1] 0 0
Evaluated at 2- and 3-years post-radiation initiation
Secondary outcome [2] 0 0
EFS (Stratum III)
Timepoint [2] 0 0
Evaluated at 2- and 3-years post-radiation initiation
Secondary outcome [3] 0 0
Radiographic response rate
Timepoint [3] 0 0
Following the completion of Induction therapy, approximately 12 weeks post-chemotherapy initiation
Secondary outcome [4] 0 0
Marker tumor response rate
Timepoint [4] 0 0
Following the completion of Induction therapy, approximately 12 weeks post-chemotherapy initiation
Secondary outcome [5] 0 0
Overall survival (OS)
Timepoint [5] 0 0
Time from initiation of radiation therapy until death by any cause, up to 10 years post-enrollment
Secondary outcome [6] 0 0
Neuroendocrine dysfunction (including growth hormone deficiency)
Timepoint [6] 0 0
Time from initiation of RT until date of diagnosis of neuroendocrine dysfunction event, up to 10 years post-enrollment
Secondary outcome [7] 0 0
Processing speed
Timepoint [7] 0 0
At 9 months (+/- 3 months), 30 months (+/- 3 months), and 60 months (+/- 3 months) after diagnosis

Eligibility
Key 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
Minimum age
3 Years
Maximum age
29 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/10/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
4/11/2033
Actual
Sample size
Target
240
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Delaware
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Idaho
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Iowa
Country [11] 0 0
United States of America
State/province [11] 0 0
Kentucky
Country [12] 0 0
United States of America
State/province [12] 0 0
Maryland
Country [13] 0 0
United States of America
State/province [13] 0 0
Michigan
Country [14] 0 0
United States of America
State/province [14] 0 0
Minnesota
Country [15] 0 0
United States of America
State/province [15] 0 0
Mississippi
Country [16] 0 0
United States of America
State/province [16] 0 0
Missouri
Country [17] 0 0
United States of America
State/province [17] 0 0
Nebraska
Country [18] 0 0
United States of America
State/province [18] 0 0
New Hampshire
Country [19] 0 0
United States of America
State/province [19] 0 0
New Jersey
Country [20] 0 0
United States of America
State/province [20] 0 0
New York
Country [21] 0 0
United States of America
State/province [21] 0 0
North Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
Ohio
Country [23] 0 0
United States of America
State/province [23] 0 0
Oregon
Country [24] 0 0
United States of America
State/province [24] 0 0
Pennsylvania
Country [25] 0 0
United States of America
State/province [25] 0 0
Rhode Island
Country [26] 0 0
United States of America
State/province [26] 0 0
Tennessee
Country [27] 0 0
United States of America
State/province [27] 0 0
Texas
Country [28] 0 0
United States of America
State/province [28] 0 0
Utah
Country [29] 0 0
United States of America
State/province [29] 0 0
Virginia
Country [30] 0 0
United States of America
State/province [30] 0 0
Washington
Country [31] 0 0
United States of America
State/province [31] 0 0
Wisconsin
Country [32] 0 0
Canada
State/province [32] 0 0
Nova Scotia
Country [33] 0 0
Canada
State/province [33] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Mohamed S Abdelbaki
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06368817