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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04684368




Registration number
NCT04684368
Ethics application status
Date submitted
15/12/2020
Date registered
24/12/2020
Date last updated
10/06/2024

Titles & IDs
Public title
A Study of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT
Scientific title
A Phase 2 Trial of Chemotherapy Followed by Response-Based Whole Ventricular &Amp; Spinal Canal Irradiation (WVSCI) for Patients With Localized Non-Germinomatous Central Nervous System Germ Cell Tumor
Secondary ID [1] 0 0
NCI-2020-13175
Secondary ID [2] 0 0
ACNS2021
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Central Nervous System Nongerminomatous Germ Cell Tumor 0 0
Choriocarcinoma 0 0
Embryonal Carcinoma 0 0
Immature Teratoma 0 0
Malignant Teratoma 0 0
Mixed Germ Cell Tumor 0 0
Pineal Region Germ Cell Tumor 0 0
Pineal Region Immature Teratoma 0 0
Pineal Region Yolk Sac Tumor 0 0
Suprasellar Germ Cell Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Testicular
Cancer 0 0 0 0
Other cancer types
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Reproductive Health and Childbirth 0 0 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Biospecimen Collection
Treatment: Drugs - Carboplatin
Treatment: Drugs - Etoposide
Other interventions - Filgrastim
Treatment: Drugs - Ifosfamide
Treatment: Surgery - Magnetic Resonance Imaging
Treatment: Drugs - Mesna
Other interventions - Pegfilgrastim
Treatment: Surgery - Peripheral Blood Stem Cell Transplantation
Other interventions - Questionnaire Administration
Treatment: Other - Radiation Therapy
Treatment: Other - Radiation Therapy
Treatment: Surgery - Second-Look Surgery
Treatment: Drugs - Thiotepa

Experimental: Plan A (chemotherapy, WVSCI, second-look surgery if needed) - See Outline in Detailed Description.

Experimental: Plan B (chemotherapy, HDCSCR, second-look surgery if needed) - See Outline in Detailed Description.


Treatment: Surgery: Biospecimen Collection
Undergo collection of CSF and blood samples

Treatment: Drugs: Carboplatin
Given IV

Treatment: Drugs: Etoposide
Given IV

Other interventions: Filgrastim
Given subcutaneously (SC) or IV

Treatment: Drugs: Ifosfamide
Given IV

Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI

Treatment: Drugs: Mesna
Given IV or orally

Other interventions: Pegfilgrastim
Given SC

Treatment: Surgery: Peripheral Blood Stem Cell Transplantation
Undergo PBSC transplant

Other interventions: Questionnaire Administration
Ancillary studies

Treatment: Other: Radiation Therapy
Undergo WVSCI radiation therapy

Treatment: Other: Radiation Therapy
Undergo radiation therapy

Treatment: Surgery: Second-Look Surgery
Undergo second-look surgery if needed

Treatment: Drugs: Thiotepa
Given IV
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Other interventions
Intervention code [4] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Failure rate
Timepoint [1] 0 0
Within 2 years of enrollment
Primary outcome [2] 0 0
Spinal failure rate
Timepoint [2] 0 0
Within 2 years of enrollment
Secondary outcome [1] 0 0
Radiographic complete response (CR)/partial response (PR) with marker normalization rate post induction/second-look surgery
Timepoint [1] 0 0
Approximately 6 to 9 months post-treatment initiation
Secondary outcome [2] 0 0
Radiographic complete response (CR)/partial response (PR) with marker normalization rate post high-dose chemotherapy with peripheral stem cell rescue (HDCSCR)
Timepoint [2] 0 0
Up to 2 years post-treatment initiation
Secondary outcome [3] 0 0
Progression-free survival (PFS)
Timepoint [3] 0 0
From enrollment until disease progression or death from any cause for patients with events, and until final follow up for those who are event free at the time of analysis, assessed up to 10 years
Secondary outcome [4] 0 0
Overall survival (OS)
Timepoint [4] 0 0
From enrollment until death from any cause for patients with events and until final follow up for those who are alive at the time of analysis, assessed up to 10 years
Secondary outcome [5] 0 0
Patterns of disease recurrence/failure
Timepoint [5] 0 0
Up to 10 years

Eligibility
Key inclusion criteria
- Patients must be >= 3 years and < 30 years at the time of study enrollment

- Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar
and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevation
of AFP above institutional normal or > 10 ng/mL or human chorionic gonadotropin (hCG)
beta > 100 mIU/mL as confirmed by Rapid Central Marker Screening Review on
APEC14B1-CNS. Suprasellar, pineal and bifocal tumors are included. (CSF tumor markers
and cytology must be within 31 days prior to enrollment and start of protocol therapy
[repeat if necessary]. Serum tumor markers, AFP and hCGbeta must be within 7 days
prior to enrollment and start of protocol therapy [repeat if necessary]). Basal
ganglia or other primary sites are excluded

- Patients with any of the following pathological elements are eligible: endodermal
sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma
and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant
elements listed above are present. Patients with only mature teratoma are excluded.
Patients with pure germinoma admixed with mature teratoma are excluded (would be
eligible for pure germinoma protocols)

- Patients must have a cranial 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 (within 31 days prior to
study enrollment and start of protocol therapy )

- Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to
enrollment. Spine MRI with and without gadolinium is recommended (within 31 days prior
to study enrollment and start of protocol therapy)

- 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

- Patients must have RAPID CENTRAL TUMOR MARKER REVIEW CSF tumor markers obtained prior
to 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

- Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to
enrollment)

- Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to
enrollment)

- Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days
prior to enrollment)

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (within 7 days
prior to enrollment):

- Age: Maximum serum creatinine (mg/dL)

- 3 to < 6 years: 0.8 (male), 0.8 (female)

- 6 to < 10 years: 1 (male), 1 (female)

- 10 to < 13 years: 1.2 (male), 1.2 (female)

- 13 to < 16 years: 1.5 (male), 1.4 (female)

- >= 16 years: male (1.7), 1.4 (female)

- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment)

- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L (within 7 days prior to enrollment)

- Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L

- Central nervous system function defined as:

- Patients with seizure disorder may be enrolled if on anticonvulsants and well
controlled

- Patients must not be in status epilepticus, coma or assisted ventilation prior to
study enrollment

- Protocol therapy must begin within 31 calendar days of definitive surgery or clinical
diagnosis, whichever is later. If a biopsy only was performed, the biopsy date will be
considered the date of definitive surgery. For patients who have a biopsy or
incomplete resection at diagnosis followed by additional surgery, the date of the last
resection will be considered the date of definitive surgery.

- 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

- NEUROCOGNITIVE FUNCTION AND QUALITY OF LIFE ASSESSMENT:

- English-, Spanish-, or French- speaking

- Note: Patients who speak a language other than English, Spanish, or French will
be allowed to participate in ACNS2021 but will not complete the neurocognitive
and quality of life assessments

- No known history of neurodevelopmental disorder prior to diagnosis of NGGCT (e.g.,
Down syndrome, fragile X, William syndrome, intellectual disability). Patients with
NF1 will be allowed to participate

- Additional eligibility criteria for the COG Standardized Neuropsychological Battery
only: must be at a site that has a psychologist to administer the battery

- Note: If not eligible for the COG Standardized Battery, patients should still
complete the Behavior Rating Inventory of Executive Function, Second Edition
(BRIEF-2), Pediatric Quality of Life Inventory (PedsQL), Adaptive Behavior
Assessment System Third Edition (ABAS-3), and Behavior Assessment System for
Children, Third Edition (BASC-3) questionnaires
Minimum age
3 Years
Maximum age
29 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with tumors located outside the ventricles (i.e., basal ganglia, thalamus)

- Patients with only mature teratoma and non-elevated markers upon tumor sampling at
diagnosis

- Patients who have received any prior tumor-directed therapy for their diagnosis of
NGGCT other than surgical intervention and corticosteroids

- Patients with metastatic disease (i.e., MRI evaluation, lumbar CSF cytology or
intraoperative evidence of dissemination)

- Female patients who are pregnant, since fetal toxicities and teratogenic effects have
been noted for several of the study drugs

- 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

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
13/07/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
21/12/2029
Actual
Sample size
Target
160
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [3] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [4] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment postcode(s) [4] 0 0
6009 - Perth
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
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
Arizona
Country [4] 0 0
United States of America
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Arkansas
Country [5] 0 0
United States of America
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California
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United States of America
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Colorado
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Connecticut
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United States of America
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Delaware
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United States of America
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District of Columbia
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United States of America
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Florida
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United States of America
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Iowa
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Kentucky
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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Nebraska
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Nevada
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New Jersey
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New York
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North Carolina
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North Dakota
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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South Dakota
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Tennessee
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Texas
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Utah
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Virginia
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Washington
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West Virginia
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United States of America
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Wisconsin
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Canada
State/province [46] 0 0
Alberta
Country [47] 0 0
Canada
State/province [47] 0 0
Manitoba
Country [48] 0 0
Canada
State/province [48] 0 0
Quebec
Country [49] 0 0
New Zealand
State/province [49] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This phase II trial studies the best approach to combine chemotherapy and radiation therapy
(RT) based on the patient's response to induction chemotherapy in patients with
non-germinomatous germ cell tumors (NGGCT) that have not spread to other parts of the brain
or body (localized). This study has 2 goals: 1) optimizing radiation for patients who respond
well to induction chemotherapy to diminish spinal cord relapses, 2) utilizing higher dose
chemotherapy followed by conventional RT in patients who did not respond to induction
chemotherapy. Chemotherapy drugs, such as carboplatin, etoposide, ifosfamide, and thiotepa,
work in different ways to stop the growth of tumor cells, either by killing the cells, by
stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high
energy x-rays or high-energy protons to kill tumor cells and shrink tumors. Studies have
shown that patients with newly-diagnosed localized NGGCT, whose disease responds well to
chemotherapy before receiving radiation therapy, are more likely to be free of the disease
for a longer time than are patients for whom the chemotherapy does not efficiently eliminate
or reduce the size of the tumor. The purpose of this study is to see how well the tumors
respond to induction chemotherapy to decide what treatment to give next. Some patients will
be given RT to the spine and a portion of the brain. Others will be given high dose
chemotherapy and a stem cell transplant before RT to the whole brain and spine. Giving
treatment based on the response to induction chemotherapy may lower the side effects of
radiation in some patients and adjust the therapy to a more efficient one for other patients
with localized NGGCT.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04684368
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Shannon M MacDonald
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04684368