Radiation Therapy Compared With Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Primary Central Nervous System (CNS) Germ Cell Tumor

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00085098
First received: June 10, 2004
Last updated: September 3, 2014
Last verified: September 2014
  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 Tumor
Central Nervous System Tumor
Biological: filgrastim
Drug: carboplatin
Drug: cisplatin
Drug: cyclophosphamide
Drug: etoposide
Radiation: radiation therapy
Phase 3

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Event-free Survival [ Time Frame: 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 ] [ Designated as safety issue: No ]

    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).



Secondary Outcome Measures:
  • Response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Toxicity and Safety as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 [ Time Frame: From the beginning of treatment, assessed up to 5 years ] [ Designated as safety issue: Yes ]
    The analysis of toxicity will focus on estimating the rates of key acute and subacute toxicity occurring during the first induction chemotherapy. Estimates will be obtained using life-table methods with an event defined as the first occurrence of a key acute or sub-acute toxicity. Patients who have progression or recurrence of disease will be censored in these analyses. The precision of the estimates of toxicity rate can be approximated by an analysis of binomial proportions.

  • Quality of Life (QOL) and Neurocognitive Assessment (NP) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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. Comparisons of each treatment group with the standard population mean, using a two-sided test with Type I error 0.025 (an adjustment for multiple comparison) will be able to detect differences from the standard mean that are 20% smaller.


Enrollment: 24
Study Start Date: January 2007
Estimated Study Completion Date: May 2019
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Radiation: radiation therapy
Patients undergo radiotherapy 5 days a week
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

Biological: filgrastim
Given by infusion or injection
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC #61462
Drug: carboplatin
Given IV over 1 hour
Other Names:
  • Paraplatin
  • NSC #241240
Drug: cisplatin
Given IV over 6 hours
Other Names:
  • Cis-diamminedichloroplatinum II
  • Platinol-AQ
  • NSC #119875
Drug: cyclophosphamide
Given IV over 1 hour
Other Names:
  • Cytoxan
  • NSC #26271
Drug: etoposide
Given IV over 2 hours
Other Names:
  • VePesid
  • Etopophos
  • VP-16
  • NSC #141540
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)
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 107 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Jeffrey C. Allen, MD New York University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00085098     History of Changes
Other Study ID Numbers: ACNS0232, CDR0000367294, COG-ACNS0232
Study First Received: June 10, 2004
Results First Received: June 7, 2013
Last Updated: September 3, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
childhood central nervous system germ cell tumor

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Carboplatin
Cisplatin
Cyclophosphamide
Etoposide
Lenograstim
Adjuvants, Immunologic
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 21, 2014