Radiation Therapy Compared With Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Primary Central Nervous System (CNS) Germ Cell Tumor
- Conditions
- Central Nervous System TumorBrain Tumor
- Interventions
- Biological: filgrastimRadiation: radiation therapy
- Registration Number
- NCT00085098
- Lead Sponsor
- Children's Oncology Group
- Brief 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.
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Regimen B (chemotherapy plus radiotherapy) radiation therapy 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 Regimen A (radiotherapy only) radiation therapy Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks. Regimen B (chemotherapy plus radiotherapy) filgrastim 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 Regimen B (chemotherapy plus radiotherapy) carboplatin 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 Regimen B (chemotherapy plus radiotherapy) cisplatin 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 Regimen B (chemotherapy plus radiotherapy) cyclophosphamide 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 Regimen B (chemotherapy plus radiotherapy) etoposide 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
- Primary Outcome Measures
Name Time Method Event-free Survival 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 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
Name Time Method Toxicity and Safety as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 From the beginning of treatment, assessed up to 5 years 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
Quality of Life (QOL) and Neurocognitive Assessment (NP) 2 years from beginning of treatment 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.
Number of Participants With a Response to Regimen B 5 years from beginning of treatment 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.
Trial Locations
- Locations (106)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
🇺🇸Dallas, Texas, United States
Driscoll Children's Hospital
🇺🇸Corpus Christi, Texas, United States
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
St. Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
M. D. Anderson Cancer Center at University of Texas
🇺🇸Houston, Texas, United States
Children's Memorial Hospital - Chicago
🇺🇸Chicago, Illinois, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
Saint Peter's University Hospital
🇺🇸New Brunswick, New Jersey, United States
St. Joseph's Hospital and Medical Center
🇺🇸Paterson, New Jersey, United States
Maimonides Cancer Center at Maimonides Medical Center
🇺🇸Brooklyn, New York, United States
University of Miami Sylvester Comprehensive Cancer Center - Miami
🇺🇸Miami, Florida, United States
Miami Children's Hospital
🇺🇸Miami, Florida, United States
CCOP - Nevada Cancer Research Foundation
🇺🇸Las Vegas, Nevada, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
San Jorge Children's Hospital
🇵🇷Santurce, Puerto Rico
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
🇺🇸Farmington, Connecticut, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Alfred I. duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Floating Hospital for Children at Tufts - New England Medical Center
🇺🇸Boston, Massachusetts, United States
Greenville Hospital Cancer Center
🇺🇸Greenville, South Carolina, United States
University of Mississippi Cancer Clinic
🇺🇸Jackson, Mississippi, United States
Palmetto Health South Carolina Cancer Center
🇺🇸Columbia, South Carolina, United States
Hopital Sainte Justine
🇨🇦Montreal, Quebec, Canada
Overlook Hospital
🇺🇸Morristown, New Jersey, United States
CCOP - Kalamazoo
🇺🇸Kalamazoo, Michigan, United States
Walter Reed Army Medical Center
🇺🇸Washington, District of Columbia, United States
Mountain States Tumor Institute at St. Luke's Regional Medical Center
🇺🇸Boise, Idaho, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Butterworth Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
CancerCare of Maine at Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Sanford Cancer Center at Sanford USD Medical Center
🇺🇸Sioux Falls, South Dakota, United States
Tulane Cancer Center Office of Clinical Research
🇺🇸Alexandria, Louisiana, United States
West Virginia University Health Sciences Center - Charleston
🇺🇸Charleston, West Virginia, United States
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
🇺🇸Birmingham, Alabama, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Oklahoma University Cancer Institute
🇺🇸Oklahoma City, Oklahoma, United States
Legacy Emanuel Hospital and Health Center and Children's Hospital
🇺🇸Portland, Oregon, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Midwest Children's Cancer Center at Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Children's Hospital Center for Cancer and Blood Disorders
🇺🇸Aurora, Colorado, United States
St. Joseph's Cancer Institute at St. Joseph's Hospital
🇺🇸Tampa, Florida, United States
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
Southern California Permanente Medical Group
🇺🇸Downey, California, United States
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
🇺🇸Long Beach, California, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
Sacred Heart Cancer Center at Sacred Heart Hospital
🇺🇸Pensacola, Florida, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Advocate Christ Medical Center
🇺🇸Oak Lawn, Illinois, United States
Lucille P. Markey Cancer Center at University of Kentucky
🇺🇸Lexington, Kentucky, United States
Cardinal Glennon Children's Hospital
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Albert Einstein Cancer Center at Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States
NYU Cancer Institute at New York University Medical Center
🇺🇸New York, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
🇺🇸New York, New York, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Stony Brook University Cancer Center
🇺🇸Stony Brook, New York, United States
Blumenthal Cancer Center at Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Medical Center - Dayton
🇺🇸Dayton, Ohio, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Rhode Island Hospital Comprehensive Cancer Center
🇺🇸Providence, Rhode Island, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
East Tennessee Children's Hospital
🇺🇸Knoxville, Tennessee, United States
Texas Tech University Health Sciences Center School of Medicine - Amarillo
🇺🇸Amarillo, Texas, United States
Baylor University Medical Center - Houston
🇺🇸Houston, Texas, United States
Children's Hospital and Regional Medical Center - Seattle
🇺🇸Seattle, Washington, United States
Cook Children's Medical Center - Fort Worth
🇺🇸Fort Worth, Texas, United States
Marshfield Clinic - Marshfield Center
🇺🇸Marshfield, Wisconsin, United States
Royal Children's Hospital
🇦🇺Parkville, Victoria, Australia
Children's & Women's Hospital of British Columbia
🇨🇦Vancouver, British Columbia, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Janeway Children's Health and Rehabilitation Centre
🇨🇦St. John's, Newfoundland and Labrador, Canada
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Loma Linda University Cancer Institute at Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Lee Cancer Care of Lee Memorial Health System
🇺🇸Fort Myers, Florida, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Ellis Fischel Cancer Center at University of Missouri - Columbia
🇺🇸Columbia, Missouri, United States
Sutter Cancer Center
🇺🇸Sacramento, California, United States
Florida Hospital Cancer Institute at Florida Hospital Orlando
🇺🇸Orlando, Florida, United States
Kosair Children's Hospital
🇺🇸Louisville, Kentucky, United States
Hollings Cancer Center at Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
C.S. Mott Children's Hospital at University of Michigan Medical Center
🇺🇸Ann Arbor, Michigan, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States