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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01602666




Registration number
NCT01602666
Ethics application status
Date submitted
18/05/2012
Date registered
21/05/2012
Date last updated
29/05/2020

Titles & IDs
Public title
Chemotherapy Followed by Radiation Therapy in Treating Younger Patients With Newly Diagnosed Localized Central Nervous System Germ Cell Tumors
Scientific title
Phase 2 Trial of Response-Based Radiation Therapy for Patients With Localized Central Nervous System Germ Cell Tumors (CNS GCT)
Secondary ID [1] 0 0
NCI-2012-01967
Secondary ID [2] 0 0
ACNS1123
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
Childhood Central Nervous System Germinoma 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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - 3-Dimensional Conformal Radiation Therapy
Treatment: Drugs - Carboplatin
Treatment: Drugs - Etoposide
Treatment: Drugs - Ifosfamide
Treatment: Other - Intensity-Modulated Radiation Therapy

Experimental: Treatment (combination chemotherapy, radiation therapy) - See Detailed Description


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

Treatment: Drugs: Carboplatin
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Drugs: Ifosfamide
Given IV

Treatment: Other: Intensity-Modulated Radiation Therapy
Undergo IMRT

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
3-year progression-free survival (PFS) rate of patients with nongerminomatous germ cell tumor (NGGCT) who were treated with reduced dose whole ventricular-field irradiation - Binomial estimate of the 3-year PFS rate. Patients who were lost to follow-up or withdrew from the trial will be counted as failures.
Timepoint [1] 0 0
3 years
Primary outcome [2] 0 0
3-year PFS rate of patients with localized CNS germinoma who were treated with reduced dose radiation therapy - Binomial estimate of the 3-year PFS rate. Patients who were lost to follow-up or withdrew from the trial will be counted as failures.
Timepoint [2] 0 0
3 years
Primary outcome [3] 0 0
Neurocognitive function using the ALTE07C1 protocol - Estimated scores for processing speed, attention/concentration, and estimated IQ at 9 months, 30 months and 60 months, separately for children and young adults who are treated with reduced radiation dose and volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum 2 (germinoma).
Estimated change over these three timepoints for processing speed, attention/concentration, and estimated IQ, separately for children and young adults who are treated with reduced radiation dose and volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum 2 (germinoma).
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Estimation of the PFS distribution of patients with NGGCT treated with involved-field radiation therapy (IFR) - Kaplan-Meier estimates will be provided. Patients who were progression free at the time of analysis (including those who were lost to follow-up or withdrew) are censored for the purpose of these analyses.
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
Estimation of the overall survival (OS) distribution of patients with NGGCT treated with IFR assessed - Kaplan-Meier estimates will be provided.
Timepoint [2] 0 0
Up to 3 years
Secondary outcome [3] 0 0
Estimation of the PFS distribution of patients with localized germinoma patients and cerebrospinal fluid (CSF) serum hCGbeta of 50 mIU/mL or less or CSF serum hCGbeta greater than 50 mIU/mL and less than or equal to 100 mIU/mL - Kaplan-Meier estimates will be provided. Patients who were progression free at the time of analysis (including those who were lost to follow-up or withdrew) are censored for the purpose of these analyses.
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [4] 0 0
Estimation of the OS distribution of patients with localized germinoma patients and CSF serum hCGbeta of 50 mIU/mL or less or CSF serum hCGbeta greater than 50 mIU/mL and less than or equal to 100 mIU/mL - Kaplan-Meier estimates will be provided.
Timepoint [4] 0 0
Up to 3 years

Eligibility
Key inclusion criteria
- Patients must be newly diagnosed with localized primary CNS NGGCT (Stratum 1) or
localized primary CNS germinoma (Stratum 2); germ cell tumors located in the
suprasellar, pineal, bifocal (pineal + suprasellar) and ventricles are eligible;
tumors present in the above mentioned locations and with unifocal parenchymal
extension are eligible

- Stratum 1(NGGCT): Patients must have one of the following criteria:

- Patients with serum and/or CSF hCGbeta > 100 mIU/mL or any elevation of
serum and/or CSF alpha-fetoprotein (AFP) > 10 ng/mL or greater than the
institutional normal are eligible, irrespective of biopsy results

- Patients with any of the following elements on biopsy/resection are
eligible, irrespective of serum and/or CSF hCGbeta and AFP levels:
endodermal sinus tumor (yolk sac), embryonal carcinoma, choriocarcinoma,
malignant/immature teratoma, and mixed GCT with malignant GCT elements

- Stratum 2 (Germinoma): Patients must have both serum and CSF markers obtained
(unless obtaining CSF is medically contraindicated) and must have one of the
following criteria to be eligible:

- Patients with institutional normal AFP (or =< 10 ng/mL if no institutional
normal exists) in both serum and CSF (unless medically contraindicated) AND
hCGbeta 5 to =< 50 mIU/mL in serum and/or CSF (unless medically
contraindicated) (only 1 is required to be elevated) are eligible; no
histologic confirmation required

- Patients with bifocal (pineal + suprasellar) involvement or pineal lesion
with diabetes insipidus (D1) 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 (unless medically contraindicated) are
eligible; no histologic confirmation required

- Patients with histologically confirmed germinoma or germinoma mixed with
mature teratoma 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 (unless medically contraindicated) are eligible

- All 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 cranial 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 cranial MRI is recommended but not required; all patients must have a
spine MRI with gadolinium obtained at diagnosis/prior to enrollment; Note: if the
spine study is performed for the first time after surgical resection or biopsy, it is
recommended to be obtained with and without gadolinium

- Lumbar CSF must be obtained prior to study enrollment unless medically
contraindicated; if a patient undergoes surgery and lumbar CSF cannot be obtained at
this time, then it should be performed at least 10 days following surgery before study
enrollment; false positive cytology can occur within 10 days of surgery; Note:
patients with positive CSF cytology obtained prior to 10 days after surgery may have
cytology repeated to determine eligibility

- Patients must have 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

- Patients must be enrolled on ALTE07C1 prior to enrollment on ACNS1123; patients must
be enrolled within 31 days of definitive diagnostic surgery (day 0) or clinical
diagnosis

- Peripheral absolute neutrophil count (ANC) >= 1,000/uL

- Platelet count >= 100,000/uL (transfusion independent)

- Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)

- Creatinine clearance or radioisotope glomular filtration rate (GFR) >= 70 mL/min/1.73
m^2 OR serum creatinine based on age/gender as follows:

- 0.8 mg/dL (2 to < 6 years of age)

- 1.0 mg/dL (6 to < 10 years of age)

- 1.2 mg/dL (10 to < 13 years of age)

- 1.5 mg/dL (male) and 1.4 mg/dL (female) (13 to < 16 years of age)

- 1.7 mg/dL (male) and 1.4 mg/dL (female) (>= 16 years of age)

- Total bilirubin =< 1.5 times upper limit of normal (ULN) for age

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5
times ULN

- Patients with seizure disorder may be enrolled if well controlled

- Patients must not be in status, coma, or assisted ventilation prior to study
enrollment
Minimum age
3 Years
Maximum age
21 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with mature teratoma or completely resected immature teratoma with normal
tumor markers are not eligible

- Patients with tumors located outside the ventricles (basal ganglia, thalamus) are not
eligible

- Patients with metastatic disease by cranial or spinal MRI evaluation or CSF cytology
(unless medically contraindicated) are not eligible

- Patients must not have received any prior tumor-directed therapy other than surgical
intervention and corticosteroids

- Female patients who are pregnant are ineligible

- Lactating females are not eligible unless they have agreed not to breastfeed their
infants

- Female patients of childbearing potential are not eligible unless a negative pregnancy
test result has been obtained

- Sexually active patients of reproductive potential are not eligible unless they have
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
N/A
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
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
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 hospital [4] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [5] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [6] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [7] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [8] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment hospital [9] 0 0
Perth Children's Hospital - Perth
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 postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
4101 - South Brisbane
Recruitment postcode(s) [6] 0 0
5006 - North Adelaide
Recruitment postcode(s) [7] 0 0
3052 - Parkville
Recruitment postcode(s) [8] 0 0
6008 - Perth
Recruitment postcode(s) [9] 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
Arizona
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
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Delaware
Country [7] 0 0
United States of America
State/province [7] 0 0
District of Columbia
Country [8] 0 0
United States of America
State/province [8] 0 0
Florida
Country [9] 0 0
United States of America
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Georgia
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United States of America
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Hawaii
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United States of America
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Idaho
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Illinois
Country [13] 0 0
United States of America
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Indiana
Country [14] 0 0
United States of America
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Iowa
Country [15] 0 0
United States of America
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Kentucky
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United States of America
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Louisiana
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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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United States of America
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Missouri
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Nevada
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New Hampshire
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New Jersey
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New Mexico
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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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United States of America
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Oklahoma
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Oregon
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United States of America
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Pennsylvania
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United States of America
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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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United States of America
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Wisconsin
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Canada
State/province [42] 0 0
British Columbia
Country [43] 0 0
Canada
State/province [43] 0 0
Manitoba
Country [44] 0 0
Canada
State/province [44] 0 0
Nova Scotia
Country [45] 0 0
Canada
State/province [45] 0 0
Ontario
Country [46] 0 0
Canada
State/province [46] 0 0
Quebec
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New Zealand
State/province [47] 0 0
Auckland
Country [48] 0 0
New Zealand
State/province [48] 0 0
Christchurch
Country [49] 0 0
Puerto Rico
State/province [49] 0 0
San Juan

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 how well chemotherapy followed by radiation therapy work in
treating younger patients with newly diagnosed central nervous system germ cell tumors that
have not spread to other parts of the brain, spinal canal, or body (localized). Drugs used as
chemotherapy, such as carboplatin, etoposide, and ifosfamide, 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 to kill tumor cells.
Giving chemotherapy followed by radiation therapy may kill more tumor cells.
Trial website
https://clinicaltrials.gov/show/NCT01602666
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ute K Bartels
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
Other publications