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

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	Biological: filgrastim Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: etoposide Radiation: radiation therapy	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Radiotherapy Alone VS. Chemotherapy Followed By Response-Based Radiotherapy For Newly Diagnosed Primary CNS Germinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Cyclophosphamide Cisplatin Etoposide Carboplatin Etoposide phosphate Filgrastim Lenograstim Granulocyte colony-stimulating factor

U.S. FDA Resources

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:

Event-free survival [ Time Frame: Six years after enrollment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response [ Time Frame: 4 cycles of chemotherapy ] [ Designated as safety issue: No ]
Toxicity [ Time Frame: Duration of protocol therapy ] [ Designated as safety issue: Yes ]
Quality of Life [ Time Frame: Two years after enrollment ] [ Designated as safety issue: No ]

Enrollment:	24
Study Start Date:	January 2007
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 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.	Radiation: radiation therapy Patients undergo radiotherapy 5 days a week
Experimental: Regimen B (chemotherapy plus radiotherapy) 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.	Biological: filgrastim Given by infusion or injection 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 Radiation: radiation therapy Patients undergo radiotherapy 5 days a week

Arms

Assigned Interventions

Active Comparator: 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.

Radiation: radiation therapy

Patients undergo radiotherapy 5 days a week

Experimental: Regimen B (chemotherapy plus radiotherapy)

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.

Biological: filgrastim

Given by infusion or injection

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

Radiation: 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 107 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

More Information

Additional Information:

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

No publications provided

Responsible Party:	Children's Oncology Group
ClinicalTrials.gov Identifier:	NCT00085098 History of Changes
Other Study ID Numbers:	ACNS0232, CDR0000367294
Study First Received:	June 10, 2004
Last Updated:	December 30, 2012
Health Authority:	United States: Federal Government

Keywords provided by Children's Oncology Group:

childhood central nervous system germ cell tumor

Additional relevant MeSH terms:

Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Germ Cell and Embryonal
Neoplasms by Site
Neoplasms
Nervous System Diseases
Neoplasms by Histologic Type
Etoposide phosphate
Cisplatin
Cyclophosphamide
Etoposide
Carboplatin
Lenograstim
Antineoplastic Agents

Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on May 16, 2013