Completed

Radiotherapy Alone Versus Chemotherapy Followed By Response-Based Radiotherapy For Newly Diagnosed Primary CNS Germinoma

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What is being tested

filgrastim

+ carboplatin
+ cisplatin
Biological
Drug
Radiation
Who is being recruted

Neoplasms
+4

+ Neoplasms by Site
+ Nervous System Diseases
From 3 to 25 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 3
Interventional
Study Start: January 2007
See protocol details

Summary

Principal SponsorChildren's Oncology Group
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner
Study start date: January 1, 2007Actual date on which the first participant was enrolled.

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.

Official TitleRadiotherapy Alone Versus Chemotherapy Followed By Response-Based Radiotherapy For Newly Diagnosed Primary CNS Germinoma 
NCT00085098
Principal SponsorChildren's Oncology Group
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
24 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are placed into groups randomly, like flipping a coin. This ensures that the study is fair and unbiased, making the results more reliable. By assigning participants by chance, researchers can better compare treatments without external influences.

Other Ways to Assign Participants
Non-randomized allocation
: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

None (Single-arm trial)
: If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants are divided into different groups, each receiving a specific treatment at the same time. This helps researchers compare how well different treatments work against each other.

Other Ways to Assign Treatments
Single-group assignment
: Everyone gets the same treatment.

Cross-over assignment
: Participants switch between treatments during the study.

Factorial assignment
: Participants receive different combinations of treatments.

Sequential assignment
: Participants receive treatments one after another in a specific order, possibly based on individual responses.

Other assignment
: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled
: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind
: Participants do not know which treatment they are receiving, but researchers do.

Double-blind
: Neither participants nor researchers know which treatment is given.

Triple-blind
: Participants, researchers, and outcome assessors do not know which treatment is given.

Quadruple-blind
: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
From 3 to 25 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Neoplasms
Neoplasms by Site
Nervous System Diseases
Nervous System Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Central Nervous System Neoplasms
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


Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
2 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
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

Given by infusion or injection

Given IV over 1 hour

Given IV over 6 hours

Given IV over 1 hour

Given IV over 2 hours

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

Patients undergo radiotherapy 5 days a week
Study Objectives
Primary Objectives

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 Objectives

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.

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

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.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 107 locations
Suspended
Lurleen Wallace Comprehensive Cancer at University of Alabama - BirminghamBirmingham, United StatesSee the location
Suspended
Phoenix Children's HospitalPhoenix, United States
Suspended
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, United States
Suspended
Southern California Permanente Medical GroupDowney, United States

Completed107 Study Centers
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