Radiation Therapy Compared With Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Primary CNS Germ Cell Tumor - Full Text View

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00085098

Purpose

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.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: etoposide Drug: filgrastim Procedure: radiation therapy	Phase III

MedlinePlus related topics: Cancer

Drug Information available for: Cyclophosphamide Carboplatin Filgrastim Etoposide Cisplatin Etoposide phosphate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control
Official Title:	Radiotherapy Alone VS. Chemotherapy Followed By Response-Based Radiotherapy For Newly Diagnosed Primary CNS Germinoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Event-free survival [ Designated as safety issue: No ]
Response [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Quality of life [ Designated as safety issue: No ]

Estimated Enrollment:	225
Study Start Date:	January 2007
Estimated Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Regimen A (radiotherapy only): Active Comparator Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks.	Procedure: radiation therapy Patients undergo radiotherapy 5 days a week
Regimen B (chemotherapy plus radiotherapy): Experimental Patients will receive a 1-hour infusion of carboplatin on days 1 and 2 and a 2-hour infusion of etoposide on days 1-3. Treatment may be repeated every 3 weeks for two courses. Within 3 weeks of completing chemotherapy, some patients may then undergo low-dose radiation therapy 5 days a week for 5 weeks. Other patients will receive a 6-hour infusion of cisplatin on day 1, a 1-hour infusion of cyclophosphamide on days 2 and 3, and infusions or injections of filgrastim beginning on day 4 and continuing until blood counts return to normal. Treatment may be repeated every 3 weeks for two courses. Patients will then undergo low-dose radiation therapy 5 days a week for 5 weeks. Some patients may undergo a second biopsy and staging to evaluate the size of the tumor and then receive radiation therapy as on Regimen A.	Drug: carboplatin Given IV over 1 hour Drug: cisplatin Given IV over 6 hours Drug: cyclophosphamide Given IV over 1 hour Drug: etoposide Given IV over 2 hours Drug: filgrastim Given by infusion or injection Procedure: radiation therapy Patients undergo radiotherapy 5 days a week

Arms

Assigned Interventions

Regimen A (radiotherapy only): Active Comparator

Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks.

Procedure: radiation therapy

Patients undergo radiotherapy 5 days a week

Regimen B (chemotherapy plus radiotherapy): Experimental

Patients will receive a 1-hour infusion of carboplatin on days 1 and 2 and a 2-hour infusion of etoposide on days 1-3. Treatment may be repeated every 3 weeks for two courses. Within 3 weeks of completing chemotherapy, some patients may then undergo low-dose radiation therapy 5 days a week for 5 weeks. Other patients will receive a 6-hour infusion of cisplatin on day 1, a 1-hour infusion of cyclophosphamide on days 2 and 3, and infusions or injections of filgrastim beginning on day 4 and continuing until blood counts return to normal. Treatment may be repeated every 3 weeks for two courses. Patients will then undergo low-dose radiation therapy 5 days a week for 5 weeks. Some patients may undergo a second biopsy and staging to evaluate the size of the tumor and then receive radiation therapy as on Regimen A.

Drug: carboplatin

Given IV over 1 hour

Drug: cisplatin

Given IV over 6 hours

Drug: cyclophosphamide

Given IV over 1 hour

Drug: etoposide

Given IV over 2 hours

Drug: filgrastim

Given by infusion or injection

Procedure: radiation therapy

Patients undergo radiotherapy 5 days a week

Show Detailed Description

Eligibility

Ages Eligible for Study:	3 Years to 25 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 (β-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)
AST or 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00085098

Show 104 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Jeffrey C. Allen, MD	New York University School of Medicine
Investigator:	Bernadine Donahue, MD	Tisch Hospital

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000367294, COG-ACNS0232
Study First Received:	June 10, 2004
Last Updated:	January 13, 2009
ClinicalTrials.gov Identifier:	NCT00085098
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

childhood central nervous system germ cell tumor

Study placed in the following topic categories:

Cisplatin
Neoplasms, Germ Cell and Embryonal
Carboplatin
Cyclophosphamide

Central Nervous System Neoplasms
Etoposide phosphate
Etoposide
Nervous System Neoplasms

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Nervous System Diseases
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions

Neoplasms
Neoplasms by Site
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009