Overview

This trial is active, not recruiting.

Conditions brain tumor, central nervous system tumor
Treatments filgrastim, carboplatin, cisplatin, cyclophosphamide, etoposide, radiation therapy
Phase phase 3
Sponsor Children's Oncology Group
Collaborator National Cancer Institute (NCI)
Start date January 2007
End date May 2009
Trial size 24 participants
Trial identifier NCT00085098, ACNS0232, CDR0000367294, COG-ACNS0232

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks.
radiation therapy
Patients undergo radiotherapy 5 days a week
(Experimental)
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
filgrastim Granulocyte Colony-Stimulating Factor
Given by infusion or injection
carboplatin Paraplatin
Given IV over 1 hour
cisplatin Cis-diamminedichloroplatinum II
Given IV over 6 hours
cyclophosphamide Cytoxan
Given IV over 1 hour
etoposide VePesid
Given IV over 2 hours
radiation therapy
Patients undergo radiotherapy 5 days a week

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
Response
time frame: Up to 5 years
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
Quality of Life (QOL) and Neurocognitive Assessment (NP)
time frame: Up to 2 years

Eligibility Criteria

Male or female participants from 3 years up to 25 years old.

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

Additional Information

Official title Radiotherapy Alone Versus Chemotherapy Followed By Response-Based Radiotherapy For Newly Diagnosed Primary CNS Germinoma
Description OBJECTIVES: Primary - Compare event-free survival and overall survival of patients with newly diagnosed primary CNS germ cell tumor treated with conventional radiotherapy alone (regimen A) vs chemotherapy followed by tumor response-based radiotherapy (regimen B). Secondary - Determine the complete response rate in patients treated with regimen B. - Determine the acute and subacute toxicity of regimen B in these patients. - Compare treatment-related morbidity, in terms of verbal learning and memory, executive functioning, and quality of life, in patients treated with these regimens. - Determine the prognostic value of baseline serum, lumbar, and intraventricular levels of human chorionic gonadotropin levels from patients treated with these regimens. - Determine the prognostic value of extent of disease (M+ vs modified M+ vs M0) on event-free survival and overall survival of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor location (pineal vs suprasellar vs pineal + suprasellar or other), and disease stage (disseminated vs occult multi-focal vs localized). Patients are randomized to 1 of 2 treatment regimens. All patients undergo an operative procedure (endoscopic biopsy, stereotactic biopsy, or open craniotomy) to confirm the diagnosis of pure germ cell germinoma followed by an intraoperative and perioperative staging evaluation. - Regimen A (radiotherapy only): Within 52 days of surgery, patients undergo standard-dose radiotherapy once daily on days 1-5 for approximately 5-6 weeks. - 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. Patients achieving a complete response (CR) proceed to reduced-dose radiotherapy. Patients with minimal residual disease (MRD), a partial response (PR), or stable disease (SD) receive chemotherapy courses 3 and 4 as outlined below. Patients with progressive disease undergo a second surgical procedure for biopsy and are restaged. Patients with a confirmed diagnosis of germ cell tumor with no change in tumor markers and no new lesions after restaging proceed to chemotherapy courses 3 and 4. - 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) subcutaneously 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 are restaged. Patients with a confirmed diagnosis of germ cell tumor after restaging undergo standard radiotherapy as in regimen A. - Reduced-dose radiotherapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiotherapy once daily on days 1-5 for 5 weeks. Treatment in both regimens continues in the absence of unacceptable toxicity or in the event that a non-germinomatous germ cell tumor is detected. Quality of life and neuropsychological function within the domains of intelligence, attention-concentration, memory, and executive functioning are assessed at 9, 30, and 60 months after diagnosis. Patients are followed every 4 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 225 patients (approximately 112 per treatment regimen) will be accrued for this study within 5 years.
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by Children's Oncology Group.