Radiotherapy Alone VS. Chemotherapy Followed By Response-Based Radiotherapy For Newly Diagnosed Primary CNS Germinoma
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.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Event-free survival
There is a potential for an early time lag in the discovery of treatment failure events in patients on regimen B. Although it is unlikely that the bias that is introduced will be large enough to noticeably influence the properties of the usual logrank test in this case, a partially-grouped logrank test 34 with grouping time of 6 months will be employed to minimize this bias.
Time from study entry to disease progression, disease recurrence or the development of new lesions, the occurrence of the second malignant neoplasm, or death from any cause, assessed up to 5 years
No
Jeffrey C. Allen, MD
Study Chair
New York University School of Medicine
United States: Federal Government
ACNS0232
NCT00085098
January 2007
Name | Location |
---|---|
Roswell Park Cancer Institute | Buffalo, New York 14263 |
Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
Walter Reed Army Medical Center | Washington, District of Columbia 20307-5000 |
University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
University of Texas Health Science Center at San Antonio | San Antonio, Texas 78284-7811 |
CCOP - Kalamazoo | Kalamazoo, Michigan 49007-3731 |
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center | Farmington, Connecticut 06360-2875 |
Penn State Cancer Institute at Milton S. Hershey Medical Center | Hershey, Pennsylvania 17033-0850 |
Sanford Cancer Center at Sanford USD Medical Center | Sioux Falls, South Dakota 57117-5039 |
Marshfield Clinic - Marshfield Center | Marshfield, Wisconsin 54449 |
Newark Beth Israel Medical Center | Newark, New Jersey 07112 |
Ellis Fischel Cancer Center at University of Missouri - Columbia | Columbia, Missouri 65203 |
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | Chapel Hill, North Carolina 27599-7570 |
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
Sutter Cancer Center | Sacramento, California 95816 |
Children's National Medical Center | Washington, District of Columbia 20010-2970 |
Children's Mercy Hospital | Kansas City, Missouri 64108 |
St. Joseph's Hospital and Medical Center | Paterson, New Jersey 07503 |
Children's Hospital of Pittsburgh | Pittsburgh, Pennsylvania 15213 |
Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
Nemours Children's Clinic | Jacksonville, Florida 32207 |
Miami Children's Hospital | Miami, Florida 33155-4069 |
All Children's Hospital | St. Petersburg, Florida 33701 |
Children's Memorial Hospital - Chicago | Chicago, Illinois 60614 |
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
Cardinal Glennon Children's Hospital | Saint Louis, Missouri 63104 |
St. Christopher's Hospital for Children | Philadelphia, Pennsylvania 19134-1095 |
St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
Driscoll Children's Hospital | Corpus Christi, Texas 78466 |
Cook Children's Medical Center - Fort Worth | Fort Worth, Texas 76104 |
Phoenix Children's Hospital | Phoenix, Arizona 85016-7710 |
Southern California Permanente Medical Group | Downey, California 90242 |
Children's Hospital Central California | Madera, California 93638-8762 |
Kosair Children's Hospital | Louisville, Kentucky 40202-3830 |
Children's Medical Center - Dayton | Dayton, Ohio 45404 |
Palmetto Health South Carolina Cancer Center | Columbia, South Carolina 29203 |
East Tennessee Children's Hospital | Knoxville, Tennessee 37901 |
Midwest Children's Cancer Center at Children's Hospital of Wisconsin | Milwaukee, Wisconsin 53226 |
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
Blumenthal Cancer Center at Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
Overlook Hospital | Summit, New Jersey 07902-0220 |
Loma Linda University Cancer Institute at Loma Linda University Medical Center | Loma Linda, California 92354 |
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital | Long Beach, California 90801 |
Lee Cancer Care of Lee Memorial Health System | Fort Myers, Florida 33901 |
Florida Hospital Cancer Institute at Florida Hospital Orlando | Orlando, Florida 32803-1273 |
Sacred Heart Cancer Center at Sacred Heart Hospital | Pensacola, Florida 32504 |
St. Joseph's Cancer Institute at St. Joseph's Hospital | Tampa, Florida 33607 |
Winship Cancer Institute of Emory University | Atlanta, Georgia 30322 |
Advocate Christ Medical Center | Oak Lawn, Illinois 60453 |
Floating Hospital for Children at Tufts - New England Medical Center | Boston, Massachusetts 02111 |
Albert Einstein Cancer Center at Albert Einstein College of Medicine | Bronx, New York 10461 |
NYU Cancer Institute at New York University Medical Center | New York, New York 10016 |
Stony Brook University Cancer Center | Stony Brook, New York 11794-8174 |
Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
Rainbow Babies and Children's Hospital | Cleveland, Ohio 44106-5000 |
Rhode Island Hospital Comprehensive Cancer Center | Providence, Rhode Island 02903 |
Hollings Cancer Center at Medical University of South Carolina | Charleston, South Carolina 29425 |
Texas Tech University Health Sciences Center School of Medicine - Amarillo | Amarillo, Texas 79106 |
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas | Dallas, Texas 75390 |
Baylor University Medical Center - Houston | Houston, Texas 77030-2399 |
Methodist Children's Hospital of South Texas | San Antonio, Texas 78229-3993 |
Primary Children's Medical Center | Salt Lake City, Utah 84113-1100 |
Saint Peter's University Hospital | New Brunswick, New Jersey 08901-1780 |
James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center | Los Angeles, California 90048-1865 |
Children's Hospital Center for Cancer and Blood Disorders | Aurora, Colorado 80045 |
Alfred I. duPont Hospital for Children | Wilmington, Delaware 19803 |
Mountain States Tumor Institute at St. Luke's Regional Medical Center | Boise, Idaho 83712-6297 |
Lucille P. Markey Cancer Center at University of Kentucky | Lexington, Kentucky 40536-0093 |
Tulane Cancer Center Office of Clinical Research | Alexandria, Louisiana 71315-3198 |
CancerCare of Maine at Eastern Maine Medical Center | Bangor, Maine 04401 |
C.S. Mott Children's Hospital at University of Michigan Medical Center | Ann Arbor, Michigan 48109-0286 |
Butterworth Hospital at Spectrum Health | Grand Rapids, Michigan 49503-2560 |
Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis, Minnesota 55404 |
University of Mississippi Cancer Clinic | Jackson, Mississippi 39216-4505 |
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis | St. Louis, Missouri 63110 |
CCOP - Nevada Cancer Research Foundation | Las Vegas, Nevada 89109-2306 |
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School | New Brunswick, New Jersey 08903 |
University of New Mexico Cancer Center | Albuquerque, New Mexico 87131-5636 |
Maimonides Cancer Center at Maimonides Medical Center | Brooklyn, New York 11219 |
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center | New York, New York 10032 |
Akron Children's Hospital | Akron, Ohio 44308-1062 |
Oklahoma University Cancer Institute | Oklahoma City, Oklahoma 73104 |
Legacy Emanuel Hospital and Health Center and Children's Hospital | Portland, Oregon 97227 |
Dell Children's Medical Center of Central Texas | Austin, Texas 78723 |
M. D. Anderson Cancer Center at University of Texas | Houston, Texas 77030-4009 |
West Virginia University Health Sciences Center - Charleston | Charleston, West Virginia 25302 |
Stanford Cancer Center | Stanford, California 94305-5824 |
University of Miami Sylvester Comprehensive Cancer Center - Miami | Miami, Florida 33136 |
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham | Birmingham, Alabama 35294 |
Greenville Hospital Cancer Center | Greenville, South Carolina 29605 |