A Phase II Study of MLN8237 (IND# 102984), a Selective Aurora A Kinase Inhibitor in Children With Recurrent/Refractory Solid Tumors and Leukemias
PRIMARY OBJECTIVE:
I. To determine the objective response rate to MLN8237 (alisertib) in children with relapsed
or refractory solid tumors and leukemias, administered once daily for 7 days every 21 days.
SECONDARY OBJECTIVES:
I. To further define and describe the toxicities of MLN8237 administered on this schedule.
II. To further characterize the pharmacokinetics of MLN8237 in children with refractory
cancer.
III. To evaluate aurora A kinase expression using immunohistochemistry in solid tumors and
leukemic blasts from tissue obtained at diagnosis and, if available, at relapse.
IV. To explore the relationship between polymorphic variations in the
UDP-glucuronosyltransferase gene UGT1A1 and exposure to MLN8237, and to assess 2 common
polymorphic variants in the aurora A kinase gene, Phe31Ile and Val57Ile.
OUTLINE: This is a multicenter study. Patients are stratified according to type of tumor
(measurable neuroblastoma vs neuroblastoma with metaiodobenzylguanidine [MIBG]-positive
lesions vs osteosarcoma vs Ewing sarcoma/primitive neuroectodermal tumor [PNET] vs
rhabdosarcoma vs non-rhabdomyosarcoma [RMS] soft tissue sarcoma vs hepatoblastoma vs
malignant germ cell tumor vs Wilms tumor vs acute myeloid leukemia [AML] vs acute
lymphoblastic leukemia [ALL] vs rhabdoid tumors).
Patients receive alisertib orally (PO) once daily (QD) on days 1-7. Treatment repeats every
21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Plasma samples are collected from all patients at baseline and periodically during course 1
for pharmacokinetic and other studies.
After completion of study therapy, patients are followed up for 5 years.
Interventional
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective response rate
Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design.
Up to 5 years
No
Yael Mosse
Principal Investigator
Children's Oncology Group
United States: Institutional Review Board
ADVL0921
NCT01154816
February 2011
Name | Location |
---|---|
Baylor College of Medicine | Houston, Texas 77030 |
Johns Hopkins University | Baltimore, Maryland 21205 |
Roswell Park Cancer Institute | Buffalo, New York 14263 |
Mayo Clinic | Rochester, Minnesota 55905 |
Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
University of Iowa Hospitals and Clinics | Iowa City, Iowa 52242 |
University of Mississippi Medical Center | Jackson, Mississippi 39216-4505 |
Washington University School of Medicine | Saint Louis, Missouri 63110 |
Medical City Dallas Hospital | Dallas, Texas 75230 |
Midwest Children's Cancer Center | Milwaukee, Wisconsin 53226 |
Sinai Hospital of Baltimore | Baltimore, Maryland 21225 |
Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
Morristown Memorial Hospital | Morristown, New Jersey 07962-1956 |
New York Medical College | Valhalla, New York 10595 |
Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
Cedars-Sinai Medical Center | Los Angeles, California 90048 |
University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
Hackensack University Medical Center | Hackensack, New Jersey 07601 |
Children's Hospital Los Angeles | Los Angeles, California 90027-0700 |
Children's National Medical Center | Washington, District of Columbia 20010-2970 |
All Children's Hospital | St. Petersburg, Florida 33701 |
Saint Jude Midwest Affiliate | Peoria, Illinois 61637 |
Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
University of Oklahoma Health Sciences Center | Oklahoma City, Oklahoma 73104 |
Legacy Emanuel Hospital and Health Center | Portland, Oregon 97227 |
St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
Driscoll Children's Hospital | Corpus Christi, Texas 78466 |
Southern California Permanente Medical Group | Downey, California 90242 |
Children's Hospital Central California | Madera, California 93638-8762 |
University of Wisconsin Hospital and Clinics | Madison, Wisconsin 53792-0001 |
Overlook Hospital | Summit, New Jersey 07902-0220 |
Winthrop University Hospital | Mineola, New York 11501 |
Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
Methodist Children's Hospital of South Texas | San Antonio, Texas 78229-3993 |
Montefiore Medical Center | Bronx, New York 10467-2490 |
Rady Children's Hospital - San Diego | San Diego, California 92123-4282 |
Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis, Minnesota 55404 |
University of New Mexico Cancer Center | Albuquerque, New Mexico 87131-5636 |
Nationwide Children's Hospital | Columbus, Ohio 43205-2696 |
Children's Hospital of Pittsburgh of UPMC | Pittsburgh, Pennsylvania 15213 |
Children's Hospital and Research Center at Oakland | Oakland, California 94609-1809 |
Presbyterian Hospital | Charlotte, North Carolina 28233-3549 |
Lee Memorial Health System | Fort Myers, Florida 33902 |
University of Alabama at Birmingham | Birmingham, Alabama 35294-3300 |
Children's Hospital of Alabama | Birmingham, Alabama 35233 |
Connecticut Children's Medical Center | Hartford, Connecticut 06106 |
University of North Carolina | Chapel Hill, North Carolina 27599 |
Nemours Children's Clinic - Pensacola | Pensacola, Florida 32504 |
Yale University | New Haven, Connecticut 06520 |
Wayne State University | Detroit, Michigan 48202 |
Mercy Children's Hospital | Toledo, Ohio 43608 |
Legacy Emanuel Children's Hospital | Portland, Oregon 97227 |
University Of Vermont | Burlington,, Vermont 05403 |
University of Texas Southwestern Medical Center | Dallas, Texas |
University of Kentucky | Lexington, Kentucky 40536-0098 |
Oregon Health and Science University | Portland, Oregon 97201 |
Tulane University Health Sciences Center | New Orleans, Louisiana 70112 |
Virginia Commonwealth University | Richmond, Virginia |
Florida Hospital | Orlando, Florida 32803 |
University of Chicago Comprehensive Cancer Center | Chicago, Illinois 60637-1470 |
Seattle Children's Hospital | Seattle, Washington 98105 |
Wake Forest University Health Sciences | Winston-Salem, North Carolina 27157 |
Childrens Memorial Hospital | Chicago, Illinois 60614 |
M D Anderson Cancer Center- Orlando | Orlando, Florida 32806 |
University of Hawaii | Honolulu, Hawaii 96813 |
Saint John's Mercy Medical Center | Saint Louis, Missouri 63141 |
Columbia University Medical Center | New York, New York 10032 |
State University of New York Upstate Medical University | Syracuse, New York 13210 |
Natalie W Bryant Cancer Center | Tulsa, Oklahoma 74136 |
Saint Vincent Hospital | Green Bay, Wisconsin 54301 |
University of Illinois | Chicago, Illinois 60612 |
Cook Children's Medical Center | Fort Worth, Texas 76104 |
The Children's Medical Center of Dayton | Dayton, Ohio 45404 |
University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami, Florida 33136 |
University of Minnesota Medical Center-Fairview | Minneapolis, Minnesota 55455 |
Children's Oncology Group | Arcadia, California 91006-3776 |
Southern Illinois University | Springfield, Illinois 62702 |
Riley Hospital for Children | Indianapolis, Indiana 46202 |
UMDNJ - Robert Wood Johnson University Hospital | New Brunswick, New Jersey 08903 |
Miller Children's Hospital | Long Beach, California 90806 |
Childrens Hospital of Orange County | Orange, California 92868-3874 |
Alfred I duPont Hospital for Children | Wilmington, Delaware 19803 |
Nemours Children's Clinic - Jacksonville | Jacksonville, Florida 32207-8426 |
Nemours Childrens Clinic - Orlando | Orlando, Florida 32806 |
Saint Joseph Children's Hospital of Tampa | Tampa, Florida 33607 |
Children's Healthcare of Atlanta - Egleston | Atlanta, Georgia 30322 |
The Childrens Mercy Hospital | Kansas City, Missouri 64108 |
Rainbow Babies and Childrens Hospital | Cleveland, Ohio 44106 |
Penn State Hershey Children's Hospital | Hershey, Pennsylvania 17033 |
Palmetto Health Richland | Columbia, South Carolina 29203 |
East Tennessee Childrens Hospital | Knoxville, Tennessee 37916 |
Children's Hospital and Medical Center of Omaha | Omaha, Nebraska 68114 |
Childrens Hospital-King's Daughters | Norfolk, Virginia 23507 |
Lucile Packard Children's Hospital Stanford University | Palo Alto, California 94304 |
University of California San Francisco Medical Center-Parnassus | San Francisco, California 94143 |
Saint Christopher's Hospital for Children | Philadelphia, Pennsylvania 19134 |
Carilion Clinic Children's Hospital | Roanoke, Virginia 24014 |
Providence Sacred Heart Medical Center and Children's Hospital | Spokane, Washington 99204 |