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A Study Evaluating Limited Target Volume Boost Irradiation and Reduced Dose Craniospinal Radiotherapy (18.00 Gy) and Chemotherapy in Children With Newly Diagnosed Standard Risk Medulloblastoma: A Phase III Double Randomized Trial


Phase 3
3 Years
21 Years
Open (Enrolling)
Both
Brain Tumor, Central Nervous System Tumor

Thank you

Trial Information

A Study Evaluating Limited Target Volume Boost Irradiation and Reduced Dose Craniospinal Radiotherapy (18.00 Gy) and Chemotherapy in Children With Newly Diagnosed Standard Risk Medulloblastoma: A Phase III Double Randomized Trial


OBJECTIVES:

Primary

- Compare event-free and overall survival of pediatric patients (3 to 7 years of age)
with newly diagnosed standard-risk medulloblastoma treated with standard-dose vs
reduced-dose craniospinal radiotherapy and posterior fossa boost vs tumor bed boost
radiotherapy in combination with chemotherapy comprising vincristine, cisplatin,
lomustine, and cyclophosphamide.

- Compare event-free and overall survival of these patients (8 to 21 years of age)
treated with standard-dose craniospinal radiotherapy and posterior fossa boost vs tumor
bed boost radiotherapy in combination with this chemotherapy regimen.

Secondary

- Compare patterns of failure in patients treated with these regimens.

- Compare the cognitive, auditory, and endocrinologic effects of these regimens in these
patients.

- Compare the audiologic and endocrinologic toxicity from these regimens in these
patients.

- Develop an optimal gene expression medulloblastoma outcome predictor.

- Assess quality of life and functional status in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients will undergo radiotherapy on days
1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). Patients receive vincristine
IV on days 8, 15, 22, 29, 36, and 43 (weeks 1-6) beginning 31 days after surgery.Patients 3
to 7 years of age are randomized to 1 of 2 chemoradiotherapy arms. Patients 8-21 years old
are assigned to arm II.

- Chemoradiotherapy:Patients will undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26,
29-33, 36-40, and 43-47 (weeks 0-6). Patients receive vincristine IV on days 8, 15, 22,
29, 36, and 43 (weeks 1-6) beginning 31 days after surgery. Patients 3 to 7 years of
age are randomized to 1 of 2 radiotherapy arms (arms I and II). Patients 8-21 years old
are assigned to arm II.

- Radiotherapy (first randomization):

- Arm I: Patients undergo reduced-dose craniospinal radiotherapy with boost.

- Arm II: Patients undergo standard-dose craniospinal radiotherapy with boost.
All patients are then randomized to 1 of 2 chemoradiotherapy arms (arms III
and IV).

- Radiotherapy boost (second randomization):

- Arm III: Patients will undergo radiotherapy boost to the entire posterior
fossa.

- Arm IV: Patients will undergo radiotherapy boost to the tumor bed only.

- Maintenance chemotherapy: Beginning 4 weeks after completion of chemoradiotherapy,
patients receive 2 different regimens of maintenance chemotherapy for a total of 9
courses. Each course in regimen A is 6 weeks (42 days) in duration. Each course in
regimen B is 4 weeks (28 days) in duration.

- Regimen A (courses 1, 2, 4, 5, 7, and 8): Patients receive oral lomustine and
cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of
weeks 11, 17, 27, 33, 43, and 49.

- Regimen B (courses 3, 6, and 9): Patients receive cyclophosphamide IV over 1 hour
on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at 3-6 months after completion of radiotherapy and at 3-4 years
after study entry. Neurocognitive function may also be assessed.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then
annually thereafter.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed medulloblastoma located in the posterior fossa

- Standard-risk disease

- Minimal volume, non-disseminated disease, defined by the following:

- Residual tumor ≤ 1.5 cm^2 confirmed by MRI with contrast imaging within 21 days
after surgery

- No metastatic disease in the head, spine, or cerebrospinal fluid (CSF) confirmed
by both of the following:

- Enhanced MRI of the spine within 5 days before surgery OR within 28 days
after surgery

- Negative cytological examination of CSF after surgery, but before study
enrollment

- Brain stem involvement allowed

PATIENT CHARACTERISTICS:

Age

- 3 to 21 at diagnosis

Performance status

- Karnofsky 50-100% (> 16 years of age) OR

- Lansky 30-100% (≤ 16 years of age)

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count > 1,500/mm^3

- Platelet count > 100,000/mm^3 (transfusion independent)

- Hemoglobin > 10 g/dL (transfusions allowed)

Hepatic

- Bilirubin < 1.5 times upper limit of normal (ULN)

- AST or ALT < 1.5 times ULN

Renal

- Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- No prior chemotherapy

Endocrine therapy

- Prior corticosteroids allowed

Radiotherapy

- No prior radiotherapy

Surgery

- See Disease Characteristics

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to event-free survival (EFS)

Outcome Description:

Time-to-event for radiation therapy question will be based on logrank test. Interim monitoring for each study question will be based on the Lan-Demets criterion, with spending function αt. The time point for 100% information is defined as two years after the last patient has enrolled. Information expended will be computed based on the current available follow-up, using the parametric cure model for A9961.

Outcome Time Frame:

Time from study entry to disease progression, disease recurrence, death from any cause, or occurrence of a second malignant neoplasm, assessed up to 3 years

Safety Issue:

No

Principal Investigator

Jeff M. Michalski, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Washington University Siteman Cancer Center

Authority:

United States: Federal Government

Study ID:

ACNS0331

NCT ID:

NCT00085735

Start Date:

April 2004

Completion Date:

Related Keywords:

  • Brain Tumor
  • Central Nervous System Tumor
  • untreated childhood medulloblastoma
  • Brain Neoplasms
  • Medulloblastoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms

Name

Location

National Naval Medical CenterBethesda, Maryland  20889
Roswell Park Cancer InstituteBuffalo, New York  14263
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywood, Illinois  60153-5500
University of Chicago Cancer Research CenterChicago, Illinois  60637
Tripler Army Medical CenterHonolulu, Hawaii  96859-5000
Hurley Medical CenterFlint, Michigan  48503
Medical City Dallas HospitalDallas, Texas  75230
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
Bronson Methodist HospitalKalamazoo, Michigan  49007
CCOP - MeritCare HospitalFargo, North Dakota  58122
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
University of Wisconsin Paul P. Carbone Comprehensive Cancer CenterMadison, Wisconsin  53792-6164
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
Newark Beth Israel Medical CenterNewark, New Jersey  07112
New York Medical CollegeValhalla, New York  10595
Deaconess Medical CenterSpokane, Washington  99210-0248
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical CenterLebanon, New Hampshire  03756-0002
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
CCOP - Scott and White HospitalTemple, Texas  76508
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
MBCCOP - LSU Health Sciences CenterNew Orleans, Louisiana  70112
Brooke Army Medical CenterFort Sam Houston, Texas  78234-6200
Children's Hospital of Orange CountyOrange, California  92668
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Mercy HospitalKansas City, Missouri  64108
St. Joseph's Hospital and Medical CenterPaterson, New Jersey  07503
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
University of California Davis Cancer CenterSacramento, California  95817
Nemours Children's ClinicJacksonville, Florida  32207
Miami Children's HospitalMiami, Florida  33155-4069
All Children's HospitalSt. Petersburg, Florida  33701
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Saint Jude Midwest AffiliatePeoria, Illinois  61637
Children's Hospital of New OrleansNew Orleans, Louisiana  70118
Cardinal Glennon Children's HospitalSaint Louis, Missouri  63104
Schneider Children's HospitalNew Hyde Park, New York  11042
St. Christopher's Hospital for ChildrenPhiladelphia, Pennsylvania  19134-1095
Driscoll Children's HospitalCorpus Christi, Texas  78466
Cook Children's Medical Center - Fort WorthFort Worth, Texas  76104
Inova Fairfax HospitalFalls Church, Virginia  22042-3300
Fletcher Allen Health Care - University Health Center CampusBurlington, Vermont  05401
Phoenix Children's HospitalPhoenix, Arizona  85016-7710
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Palmetto Health South Carolina Cancer CenterColumbia, South Carolina  29203
East Tennessee Children's HospitalKnoxville, Tennessee  37901
Covenant Children's HospitalLubbock, Texas  79410
Children's Hospital of the King's DaughtersNorfolk, Virginia  23507
Midwest Children's Cancer Center at Children's Hospital of WisconsinMilwaukee, Wisconsin  53226
Arizona Cancer Center at University of Arizona Health Sciences CenterTucson, Arizona  85724
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Carol G. Simon Cancer Center at Morristown Memorial HospitalMorristown, New Jersey  07962
Winthrop University HospitalMineola, New York  11501
Loma Linda University Cancer Institute at Loma Linda University Medical CenterLoma Linda, California  92354
Jonathan Jaques Children's Cancer Center at Miller Children's HospitalLong Beach, California  90801
Kaiser Permanente Medical Center - OaklandSacramento, California  95825
Yale Cancer CenterNew Haven, Connecticut  06520-8028
Lee Cancer Care of Lee Memorial Health SystemFort Myers, Florida  33901
Broward General Medical Center Cancer CenterFt. Lauderdale, Florida  33316
University of Florida Shands Cancer CenterGainesville, Florida  32610-0232
Nemours Children's Clinic - OrlandoOrlando, Florida  32806
Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlando, Florida  32803-1273
St. Joseph's Cancer Institute at St. Joseph's HospitalTampa, Florida  33607
St. Vincent Indianapolis HospitalIndianapolis, Indiana  46260
Blank Children's HospitalDes Moines, Iowa  50309
Floating Hospital for Children at Tufts - New England Medical CenterBoston, Massachusetts  02111
Breslin Cancer Center at Ingham Regional Medical CenterLansing, Michigan  48910
Hackensack University Medical Center Cancer CenterHackensack, New Jersey  07601
Albert Einstein Cancer Center at Albert Einstein College of MedicineBronx, New York  10461
NYU Cancer Institute at New York University Medical CenterNew York, New York  10016
Stony Brook University Cancer CenterStony Brook, New York  11794-8174
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Presbyterian Cancer Center at Presbyterian HospitalCharlotte, North Carolina  28233-3549
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Rainbow Babies and Children's HospitalCleveland, Ohio  44106-5000
Toledo HospitalToledo, Ohio  43606
Rhode Island Hospital Comprehensive Cancer CenterProvidence, Rhode Island  02903
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Texas Tech University Health Sciences Center School of Medicine - AmarilloAmarillo, Texas  79106
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390
Baylor University Medical Center - HoustonHouston, Texas  77030-2399
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Naval Medical Center - PortsmouthPortsmouth, Virginia  23708-2197
Providence Cancer Center at Sacred Heart Medical CenterSpokane, Washington  99220-2555
Edwards Comprehensive Cancer Center at Cabell Huntington HospitalHuntington, West Virginia  25701
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
Saint Peter's University HospitalNew Brunswick, New Jersey  08901-1780
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
Greenebaum Cancer Center at University of Maryland Medical CenterBaltimore, Maryland  21201
UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680
Memorial Cancer Institute at Memorial Regional HospitalHollywood, Florida  33021
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical CenterLos Angeles, California  90048-1865
Childrens Hospital Los AngelesLos Angeles, California  90027
Children's Hospital and Research Center OaklandOakland, California  94609
Lucile Packard Children's Hospital at Stanford University Medical CenterPalo Alto, California  95798
Rady Children's Hospital - San DiegoSan Diego, California  92123-4282
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Alfred I. duPont Hospital for ChildrenWilmington, Delaware  19803
M.D. Anderson Cancer Center at OrlandoOrlando, Florida  32806
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston CampusAtlanta, Georgia  30322
MBCCOP - Medical College of Georgia Cancer CenterAugusta, Georgia  30912-3730
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical CenterSavannah, Georgia  31403-3089
Mountain States Tumor Institute at St. Luke's Regional Medical CenterBoise, Idaho  83712-6297
Keyser Family Cancer Center at Advocate Hope Children's HospitalOak Lawn, Illinois  60453
Advocate Lutheran General Cancer Care CenterPark Ridge, Illinois  60068-1174
Simmons Cooper Cancer InstituteSpringfield, Illinois  62794-9677
Lucille P. Markey Cancer Center at University of KentuckyLexington, Kentucky  40536-0093
Tulane Cancer Center Office of Clinical ResearchAlexandria, Louisiana  71315-3198
CancerCare of Maine at Eastern Maine Medical CenterBangor, Maine  04401
Maine Children's Cancer Program at Barbara Bush Children's HospitalScarborough, Maine  04074-9308
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer InstituteBoston, Massachusetts  02115
C.S. Mott Children's Hospital at University of Michigan Medical CenterAnn Arbor, Michigan  48109-0286
Masonic Cancer Center at University of MinnesotaMinneapolis, Minnesota  55455
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, Minnesota  55404
Children's Hospitals and Clinics of Minnesota - St. PaulSt. Paul, Minnesota  55102-2392
University of Mississippi Cancer ClinicJackson, Mississippi  39216-4505
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
Children's HospitalOmaha, Nebraska  68114-4113
CCOP - Nevada Cancer Research FoundationLas Vegas, Nevada  89109-2306
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Albany Medical Center HospitalAlbany, New York  12208-3419
Herbert Irving Comprehensive Cancer Center at Columbia University Medical CenterNew York, New York  10032
Akron Children's HospitalAkron, Ohio  44308-1062
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Dayton Children's - DaytonDayton, Ohio  45404-1815
Tod Children's HospitalYoungstown, Ohio  44501
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Knight Cancer Institute at Oregon Health and Science UniversityPortland, Oregon  97239-3098
Geisinger Cancer Institute at Geisinger HealthDanville, Pennsylvania  17822-0001
Penn State Children's HospitalHershey, Pennsylvania  17033-0850
Dell Children's Medical Center of Central TexasAustin, Texas  78723
M. D. Anderson Cancer Center at University of TexasHouston, Texas  77030-4009
Virginia Commonwealth University Massey Cancer CenterRichmond, Virginia  23298-0037
Carilion Medical Center for Children at Roanoke Community HospitalRoanoke, Virginia  24014
Madigan Army Medical Center - TacomaTacoma, Washington  98431
West Virginia University Health Sciences Center - CharlestonCharleston, West Virginia  25302
Gundersen Lutheran Center for Cancer and BloodLa Crosse, Wisconsin  54601
Riley's Children Cancer Center at Riley Hospital for ChildrenIndianapolis, Indiana  46202-5225
Massachusetts General HospitalBoston, Massachusetts  02114-2617
University of Miami Sylvester Comprehensive Cancer Center - MiamiMiami, Florida  33136
Lehigh Valley Hospital - MuhlenbergBethlehem, Pennsylvania  18017
T.C. Thompson Children's HospitalChattanooga, Tennessee  37403
Connecticut Children's Medical CenterHartford, Connecticut  06106
Children's Hospital Colorado Center for Cancer and Blood DisordersAurora, Colorado  80045
Nemours Children's Clinic - PensacolaPensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum HealthGrand Rapids, Michigan  49503
Mercy Children's HospitalToledo, Ohio  43608
Legacy Emanuel Children's HospitalPortland, Oregon  97227
BI-LO Charities Children's Cancer CenterGreenville, South Carolina  29605
Children's Hospital of Alabama at University of Alabama at BirminghamBirmingham, Alabama  35233