Temozolomide and Irinotecan Hydrochloride With or Without Bevacizumab in Treating Young Patients With Recurrent or Refractory Medulloblastoma or CNS Primitive Neuroectodermal Tumors
Temozolomide With Irinotecan Versus Temozolomide, Irinotecan Plus Bevacizumab (NSC# 704865) for Recurrent/Refractory Medulloblastoma/CNS PNET of Childhood, a COG Randomized Phase II Screening Trial
7 other identifiers
interventional
108
5 countries
158
Brief Summary
This randomized phase II trial studies how well giving temozolomide and irinotecan hydrochloride together with or without bevacizumab works in treating young patients with recurrent or refractory medulloblastoma or central nervous system (CNS) primitive neuroectodermal tumors. Drugs used in chemotherapy, such as temozolomide and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether temozolomide and irinotecan hydrochloride are more effective with or without bevacizumab in treating medulloblastoma or CNS primitive neuroectodermal tumors.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Nov 2010
Longer than P75 for phase_2
158 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 7, 2010
CompletedFirst Posted
Study publicly available on registry
October 8, 2010
CompletedStudy Start
First participant enrolled
November 22, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2017
CompletedResults Posted
Study results publicly available
September 13, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2021
CompletedJuly 23, 2021
June 1, 2021
7.1 years
October 7, 2010
February 5, 2019
July 1, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
Overall Survival
Percentage Probability of remaining alive 5 years after enrollment estimated by the method of Kaplan and Meier
Up to 5 years after enrollment
Secondary Outcomes (2)
Response
Up to 12 cycles of therapy (11 months)
Event-free Survival
Up to 5 years after enrollment
Study Arms (2)
Arm I (temozolomide, irinotecan hydrochloride)
EXPERIMENTALPatients receive temozolomide PO and irinotecan hydrochloride IV over 90 minutes on days 1-5.
Arm II (temozolomide, irinotecan hydrochloride, bevacizumab)
EXPERIMENTALPatients receive temozolomide PO and irinotecan hydrochloride IV as in arm I and bevacizumab IV over 30-90 minutes on days 1 and 15.
Interventions
Given IV
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy; patients with pineoblastoma are eligible
- Patients must have had histologic verification of the malignancy at original diagnosis or at the time of recurrence
- Patients must have clear residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) OR diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular diameters
- All patients must have a brain MRI with and without gadolinium and a spine MRI with gadolinium performed within 2 weeks prior to study enrollment
- Patients must have a Lansky or Karnofsky performance status score of \>= 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2 (use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age)
- Patients must have a life expectancy of \>= 8 weeks
- Patients must have experienced at least one and at most two relapses prior to study enrollment; patients with primary refractory disease are eligible
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea)
- Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent; at least 3 weeks for biologic agents with a long half life, such as antibodies
- External beam radiation therapy (XRT): Must not have received craniospinal radiotherapy within 24 weeks prior to study entry; the tumor designated as "measurable" for protocol purposes must not have received radiation within 12 weeks prior to study entry); focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry
- Stem cell transplant (SCT): For autologous SCT, \>= 3 months must have elapsed prior to study entry
- Study specific limitations on prior therapy:
- Patients must not have previously received bevacizumab, irinotecan, temozolomide or other anti-vascular endothelial growth factor (VEGF) inhibitor
- Patients must not be taking enzyme-inducing antiepileptic medicines within 1 week of study entry
- +35 more criteria
You may not qualify if:
- Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study
- Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry
- Patients must not have a known bleeding diathesis or coagulopathy
- Patients must not have had significant vascular disease (eg, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study entry
- Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome); testing is not required in patients without thrombophilic history
- Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment
- Patients with a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months are not eligible
- Patients must not have serious and inadequately controlled cardiac arrhythmia
- Female patients who are pregnant are not eligible for this study
- Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed
- Female patients of childbearing potential must have a negative pregnancy test
- Sexually active patients of childbearing potential must agree to use an effective method of contraception during the study and for at least 6 months after the completion of bevacizumab therapy
- Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (158)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
Phoenix Childrens Hospital
Phoenix, Arizona, 85016, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205, United States
Kaiser Permanente Downey Medical Center
Downey, California, 90242, United States
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
Valley Children's Hospital
Madera, California, 93636, United States
Kaiser Permanente-Oakland
Oakland, California, 94611, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
Sutter Medical Center Sacramento
Sacramento, California, 95816, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Rady Children's Hospital - San Diego
San Diego, California, 92123, United States
UCSF Medical Center-Parnassus
San Francisco, California, 94143, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Connecticut Children's Medical Center
Hartford, Connecticut, 06106, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Lee Memorial Health System
Fort Myers, Florida, 33901, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908, United States
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
AdventHealth Orlando
Orlando, Florida, 32803, United States
Nemours Children's Clinic - Orlando
Orlando, Florida, 32806, United States
Orlando Health Cancer Institute
Orlando, Florida, 32806, United States
Nemours Children's Hospital
Orlando, Florida, 32827, United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607, United States
Saint Mary's Hospital
West Palm Beach, Florida, 33407, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322, United States
Memorial Health University Medical Center
Savannah, Georgia, 31404, United States
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813, United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
University of Illinois
Chicago, Illinois, 60612, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, 60453, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Blank Children's Hospital
Des Moines, Iowa, 50309, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Norton Children's Hospital
Louisville, Kentucky, 40202, United States
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112, United States
Children's Hospital New Orleans
New Orleans, Louisiana, 70118, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Michigan State University Clinical Center
East Lansing, Michigan, 48824-7016, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Columbia Regional
Columbia, Missouri, 65201, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
University Medical Center of Southern Nevada
Las Vegas, Nevada, 89102, United States
Sunrise Hospital and Medical Center
Las Vegas, Nevada, 89109, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135, United States
Summerlin Hospital Medical Center
Las Vegas, Nevada, 89144, United States
Nevada Cancer Research Foundation NCORP
Las Vegas, Nevada, 89169, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Saint Barnabas Medical Center
Livingston, New Jersey, 07039, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Saint Peter's University Hospital
New Brunswick, New Jersey, 08901, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903, United States
Newark Beth Israel Medical Center
Newark, New Jersey, 07112, United States
Overlook Hospital
Summit, New Jersey, 07902, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87102, United States
Albany Medical Center
Albany, New York, 12208, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Rochester
Rochester, New York, 14642, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
New York Medical College
Valhalla, New York, 10595, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204, United States
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227, United States
Legacy Emanuel Hospital and Health Center
Portland, Oregon, 97227, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
Penn State Children's Hospital
Hershey, Pennsylvania, 17033, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Prisma Health Richland Hospital
Columbia, South Carolina, 29203, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605, United States
Greenville Cancer Treatment Center
Greenville, South Carolina, 29605, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
Driscoll Children's Hospital
Corpus Christi, Texas, 78411, United States
Medical City Dallas Hospital
Dallas, Texas, 75230, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
El Paso Children's Hospital
El Paso, Texas, 79905, United States
Brooke Army Medical Center
Fort Sam Houston, Texas, 78234, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Covenant Children's Hospital
Lubbock, Texas, 79410, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
University of Vermont and State Agricultural College
Burlington, Vermont, 05405, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
John Hunter Children's Hospital
Hunter Regional Mail Centre, New South Wales, 2310, Australia
Sydney Children's Hospital
Randwick, New South Wales, 2031, Australia
The Children's Hospital at Westmead
Westmead, New South Wales, 2145, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029, Australia
Royal Children's Hospital-Brisbane
Herston, Queensland, 4029, Australia
Queensland Children's Hospital
South Brisbane, Queensland, 4101, Australia
Princess Margaret Hospital for Children
Perth, Western Australia, 6008, Australia
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8, Canada
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4, Canada
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9, Canada
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8, Canada
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5, Canada
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7, Canada
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1, Canada
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4, Canada
Centre Hospitalier Universitaire de Quebec
Québec, G1V 4G2, Canada
Starship Children's Hospital
Grafton, Auckland, 1145, New Zealand
Christchurch Hospital
Christchurch, 8011, New Zealand
University Pediatric Hospital
San Juan, 00926, Puerto Rico
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Adam S Levy
Children's Oncology Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 7, 2010
First Posted
October 8, 2010
Study Start
November 22, 2010
Primary Completion
December 31, 2017
Study Completion
June 30, 2021
Last Updated
July 23, 2021
Results First Posted
September 13, 2019
Record last verified: 2021-06