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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00085098




Registration number
NCT00085098
Ethics application status
Date submitted
10/06/2004
Date registered
11/06/2004
Date last updated
7/09/2018

Titles & IDs
Public title
Radiation Therapy Compared With Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Primary Central Nervous System (CNS) Germ Cell Tumor
Scientific title
Radiotherapy Alone Versus Chemotherapy Followed By Response-Based Radiotherapy For Newly Diagnosed Primary CNS Germinoma
Secondary ID [1] 0 0
CDR0000367294
Secondary ID [2] 0 0
ACNS0232
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain Tumor 0 0
Central Nervous System Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - filgrastim
Treatment: Drugs - carboplatin
Treatment: Drugs - cisplatin
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - etoposide
Treatment: Other - radiation therapy

Experimental: Regimen A (radiotherapy only) - Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks.

Experimental: Regimen B (chemotherapy plus radiotherapy) - Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses.
Within 3 weeks of completing chemotherapy, patients with CR undergo low-dose radiation therapy 5 days a week for 5 weeks. Patients with MRD, a PR, or SD receive chemotherapy courses 3 and 4 as outlined below.
Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF), subcutaneous (SC) or IV beginning on day 4 and continuing until blood counts recover.
Treatment repeats every 21 days for 2 courses. Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or progressive disease (PD) are restaged and may undergo standard radiation therapy as in regimen A. Reduced-dose radiation therapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks


Other interventions: filgrastim
Given by infusion or injection

Treatment: Drugs: carboplatin
Given IV over 1 hour

Treatment: Drugs: cisplatin
Given IV over 6 hours

Treatment: Drugs: cyclophosphamide
Given IV over 1 hour

Treatment: Drugs: etoposide
Given IV over 2 hours

Treatment: Other: radiation therapy
Patients undergo radiotherapy 5 days a week

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free Survival - Data will be summarized as number of patients in the following categories at the time of data cutoff for analyses of 3-year EFS: 1)Experienced a qualifying event (QE) (see below);2)Event-free through 3 years of follow-up;3)Event-free until data cutoff (if less than 3 years of follow-up);4)Withdrew from study;5)Lost to follow-up.
QEs: 1)disease progression, defined as increase >= 40% in tumor volume or >= 25% in tumor area of target lesions;2)development of new lesions;3)occurrence of a second malignant neoplasm, defined as a malignancy with different histological type from trial-qualifying diagnosis;4)death from any cause.
Stat. analyses will be based on time from enrollment to the earliest of: 1)occurrence of any of the QEs;2)withdrawal from study or lost to follow-up;3)completion of three years of follow-up event-free;4)data cutoff for completion of the statistical analyses for the protocol's primary objective.
NOTE: Reported data are through May 2009 (see Caveats section).
Timepoint [1] 0 0
Study enrollment until date of earliest qualifying event (QE), date last known to be QE-free if the patient is followed for less than three years and is QE-free at the time of analysis, or 3 years if the patient is QE-free at 3 years
Secondary outcome [1] 0 0
Number of Participants With a Response to Regimen B - To assess the complete response rate to pre-radiotherapy chemotherapy (Reg B only). Response was determined after completing 2-4 cycles of chemotherapy on Reg B. Complete Response (CR) is defined as disappearance of all target lesions.
Timepoint [1] 0 0
5 years from beginning of treatment
Secondary outcome [2] 0 0
Toxicity and Safety as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 - The analysis of toxicity will focus on estimating the rates of key acute and subacute toxicity occurring during the first induction chemotherapy. The list of toxicities of interest include Anemia or Febrile Neutropenia; Nausea or Vomiting; Infections and Infestations; Neutrophil or White blood count decrease; and Hypokalemia or Hyponatremia
Timepoint [2] 0 0
From the beginning of treatment, assessed up to 5 years
Secondary outcome [3] 0 0
Quality of Life (QOL) and Neurocognitive Assessment (NP) - The primary endpoints for QOL and NP assessments will be the global scale value from each of these instruments at the two-year time point. Analyses of subscales (if they exist) and of assessments at other times will be of secondary interest. It is assumed that scale values are standardized to a reference normal population. The scores range from 0 to 100 with higher score reflecting better QoL or neurocognitive assessment.
Timepoint [3] 0 0
2 years from beginning of treatment

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS:

- Histologically confirmed primary CNS pure germ cell tumor

- Diagnosed within the past 31 days

- Meets any 1 OR none (i.e., M0 [localized disease]) of the following staging criteria:

- M+ (disseminated disease)

- Leptomeningeal or intraventricular metastases visualized on MRI scans of the
brain and spine

- Clumps of tumor cells on lumbar cerebrospinal fluid (CSF) cytology

- Visible tumor studding the walls of the lateral or third ventricles noted
during endoscopy or surgery

- Primary tumor arising within the parenchyma of the brain, brainstem, or
spinal cord

- Measurable multi-focal tumors arising in both the pineal and suprasellar
regions (i.e., multiple midline tumors)

- Infiltrative, intra-axial extension on brain MRI > 1 cm beyond enhancing
tumor

- Modified M+ (occult multi-focal disease)

- M0 at diagnosis with a localized pineal region tumor with signs and symptoms
of diabetes insipidus without measurable disease in the suprasellar region

- Lumbar CSF assay meeting criteria for the following marker profiles:

- Serum and CSF beta human chorionic gonadotropin (ß-HCG) = 50 IU/dL

- Serum alpha fetoprotein (AFP) = 10 IU/L AND = institutional norm

- CSF AFP = 2.0 IU/L AND = institutional norm

PATIENT CHARACTERISTICS:

Age

- 3 to 25

Performance status

- Not specified

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count > 1,000/mm^3

- Platelet count > 100,000/mm^3 (transfusion independent)

- Hemoglobin > 10.0 g/dL (transfusion allowed)

Hepatic

- Bilirubin = 1.5 times upper limit of normal (ULN)

- aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 times ULN

Renal

- Creatinine adjusted according to age as follows*:

- No greater than 0.4 mg/dL (= 5 months)

- No greater than 0.5 mg/dL (6 months -11 months)

- No greater than 0.6 mg/dL (1 year-23 months)

- No greater than 0.8 mg/dL (2 years-5 years)

- No greater than 1.0 mg/dL (6 years-9 years)

- No greater than 1.2 mg/dL (10 years-12 years)

- No greater than 1.4 mg/dL (13 years and over [female])

- No greater than 1.5 mg/dL (13 years to 15 years [male])

- No greater than 1.7 mg/dL (16 years and over [male]) AND

- Creatinine clearance OR radioisotope glomerular filtration rate > 70 mL/min

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Euthyroid (with or without levothyroxine sodium therapy) as determined by normal T4 ±
thyroid-stimulating hormone levels*

- Diabetes insipidus allowed provided patient is relatively stable on desmopressin
acetate

- Normal endogenous cortisol function*

- Adequate antidiuretic hormone reserves* NOTE: *Unless receiving replacement therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- Not specified

Endocrine therapy

- Concurrent replacement hormones allowed (e.g., corticosteroids, levothyroxine sodium,
and desmopressin acetate)

Radiotherapy

- Not specified

Surgery

- Prior surgery for germ cell tumor allowed

Other

- No other prior therapy for germ cell tumor

- Concurrent anticonvulsants allowed
Minimum age
3 Years
Maximum age
25 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Royal Children's Hospital - Brisbane
Recruitment hospital [2] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [3] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
4029 - Brisbane
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment postcode(s) [3] 0 0
6001 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arizona
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Arkansas
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California
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Colorado
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Connecticut
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Delaware
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District of Columbia
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Florida
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Georgia
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Idaho
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Illinois
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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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Nevada
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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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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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Washington
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West Virginia
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Wisconsin
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
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Newfoundland and Labrador
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Canada
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Ontario
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Canada
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Quebec
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Puerto Rico
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Santurce

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
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in
chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or
die. It is not yet known whether radiation therapy alone is as effective as chemotherapy plus
radiation therapy in treating germ cell tumor.

PURPOSE: This randomized phase III trial is studying radiation therapy alone to see how well
it works compared to chemotherapy and radiation therapy in treating patients with newly
diagnosed primary CNS germ cell tumor.
Trial website
https://clinicaltrials.gov/show/NCT00085098
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jeffrey C. Allen, MD
Address 0 0
NYU Langone Health
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