Trial record 1 of 1 for:    ADVL0921
Previous Study | Return to List | Next Study

Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01154816
First received: June 30, 2010
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

This phase II trial is studying the side effects of and how well alisertib works in treating young patients with relapsed or refractory solid tumors or leukemia. Alisertib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Childhood Hepatoblastoma
Previously Treated Childhood Rhabdomyosarcoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Malignant Germ Cell Tumor
Recurrent Childhood Rhabdomyosarcoma
Recurrent Childhood Soft Tissue Sarcoma
Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Recurrent Neuroblastoma
Recurrent Osteosarcoma
Recurrent Wilms Tumor and Other Childhood Kidney Tumors
Drug: alisertib
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of MLN8237 (IND# 102984), a Selective Aurora A Kinase Inhibitor in Children With Recurrent/Refractory Solid Tumors and Leukemias

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Objective response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Incidence of adverse events graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Toxicity tables constructed to summarize the observed incidence in each reporting period by type of toxicity and grade. Relative frequency of each type of toxicity quantified as the number of toxicity-evaluable cycles in which the AE was noted at >= grade 3 considered by the treating physician to be possibly, probably or definitely related to alisertib divided by the number toxicity-evaluable cycles administered to patients enrolled on the trial. In addition to the tabular presentation of the data, any adverse experience that results in the filing of an AdEERS report will be identified.

  • Pharmacokinetic parameters of alisertib, including systemic exposure, drug clearance, and other pharmacokinetic parameters [ Time Frame: During the first cycle prior to drug administration and on days 1, 4, and 7 ] [ Designated as safety issue: No ]
    The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).


Estimated Enrollment: 228
Study Start Date: February 2011
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (alisertib)
Patients receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Drug: alisertib
Given orally
Other Names:
  • Aurora A kinase inhibitor MLN8237
  • MLN8237
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have had histologic verification of malignancy at original diagnosis or at relapse, to include any of the following malignancies (no other histology is eligible):

    • Neuroblastoma- measurable
    • Neuroblastoma- MIBG evaluable
    • Rhabdomyosarcoma
    • Osteosarcoma
    • Ewing sarcoma/Peripheral PNET
    • Non-RMS soft tissue sarcoma
    • Hepatoblastoma
    • Malignant germ cell tumor
    • Wilms tumor
    • Acute lymphoblastic leukemia
    • Acute myelogenous leukemia
    • Rhabdoid malignancy
  • Disease status for solid tumor patients:

    • Patients must have radiographically measurable disease (with the exception of neuroblastoma)
    • Measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 20 mm in at least one dimension; for spiral CT, measurable disease is defined as a minimum diameter of 10 mm in at least one dimension
    • Note: The following do not qualify as measurable disease:

      • Malignant fluid collections (e.g., ascites, pleural effusions)
      • Bone marrow infiltration
      • Lesions detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans)
      • Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
      • Previously irradiated lesions that have not demonstrated clear progression post radiation
    • Patients with neuroblastoma who do not have measurable disease but have MIBG+ evaluable disease are eligible
  • Disease status for leukemia patients:

    • Patients with leukemia must be recurrent or refractory to at least two prior induction or treatment regimens, in addition to the following criteria:
    • Acute lymphoid leukemia:

      • 25% blasts in the bone marrow (M3 bone marrow), excluding patients with known central nervous system (CNS) disease
    • Acute myeloid leukemia according to FAB classification

      • ≥ 5 % blasts in the bone marrow (M2/M3 bone marrow); excluding patients with known CNS disease
  • Rhabdoid tumors:

    • To be eligible for enrollment in the rhabdoid tumors stratum, the patient must have a solid tumor where the institutional pathological evaluation of the tumor at initial diagnosis or relapse has confirmed:

      • Morphology and immunophenotypic panel consistent with rhabdoid tumor (required)
      • Loss of SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1 (INI1) confirmed by immunohistochemistry, or
      • Molecular confirmation of tumor-specific bi-allelic INI1 loss/mutation if INI1 immunohistochemistry is not available; note that molecular confirmation of tumor-specific bi-allelic INI1 loss/mutation is encouraged in cases where INI1 immunohistochemistry is equivocal
  • Patients must have a Lansky or Karnofsky performance status score of ≥ 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age; Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study enrollment
  • Myelosuppressive chemotherapy:

    • Solid tumors:

      • Patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
    • Leukemia:

      • Patients with leukemia who relapse while receiving standard maintenance therapy will not be required to have a waiting period before enrollment onto this study
      • Patients who relapse while they are not receiving standard maintenance therapy must have completely recovered from all acute toxic effects of chemotherapy, immunotherapy or radiotherapy prior to study enrollment; at least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea
      • Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of MLN8237
  • At least 7 days must have elapsed since the completion of therapy with a growth factor; at least 14 days must have elapsed after receiving pegfilgrastim
  • At least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
  • At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
  • ≥ 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); ≥ 6 weeks must have elapsed since treatment with therapeutic doses of MIBG; ≥ 6 months must have elapsed if prior craniospinal XRT was received, if ≥ 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; ≥ 6 weeks must have elapsed if other substantial bone marrow irradiation was given
  • No evidence of active graft vs. host disease and ≥ 3 months must have elapsed since transplant
  • For patients with solid tumors without bone marrow involvement:

    • Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
    • Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
    • Hemoglobin > 8.0 g/dL (may receive red blood cell [RBC] transfusions)
  • For patients with solid tumors and known bone marrow metastatic disease:

    • Peripheral absolute neutrophil count (ANC) ≥ 750/mm^3
    • Platelet count ≥ 50,000/mm^3
    • Hemoglobin ≥ 8.0 g/dL
    • Transfusions are permitted to meet both the platelet and hemoglobin criteria; patients must not be known to be refractory to red blood cell or platelet transfusions
  • Patients with leukemia must not be known to be refractory to red blood cell or platelet transfusions
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

    • 1 to < 2 years: 0.6
    • 2 to < 6 years: 0.8
    • 6 to < 10 years: 1
    • 10 to < 13 years: 1.2
    • 13 to < 16 years: 1.5 (male), 1.4 (female)
    • >= 16 years: 1.7 (male), 1.4 (female)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) ≤ 5.0 x ULN for age (≤ 225 U/L); for the purpose of this study, the ULN for SGPT is 45 U/L
  • Serum albumin ≥ 2 g/dL
  • All patients and/or their parents or legal guardians must sign a written informed consent

Exclusion Criteria:

  • Patients who are pregnant or breast-feeding are not eligible for this study; negative pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy; breastfeeding women are excluded
  • Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment (14 days if pegfilgrastim)
  • Patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible
  • Patients who are currently receiving another investigational drug are not eligible
  • Patients who are currently receiving other anti-cancer agents are not eligible
  • Use of daily benzodiazepine therapy excludes a patient from being eligible because of the potential benzodiazepine-like effects of MLN8237
  • Patients who are currently receiving digoxin, cyclosporine, tacrolimus, or sirolimus are not eligible
  • Patients who are unable to swallow tablets are not eligible
  • Patients who have an uncontrolled infection are not eligible
  • Leukemia patients with CNS disease are not eligible
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01154816

  Hide Study Locations
Locations
United States, Alabama
Children's Hospital of Alabama
Birmingham, Alabama, United States, 35233
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Southern California Permanente Medical Group
Downey, California, United States, 90242
Miller Children's Hospital
Long Beach, California, United States, 90806
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Children's Hospital Central California
Madera, California, United States, 93636-8762
Childrens Hospital of Orange County
Orange, California, United States, 92868-3874
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States, 94304
Rady Children's Hospital - San Diego
San Diego, California, United States, 92123
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States, 94143
United States, Connecticut
Connecticut Children's Medical Center
Hartford, Connecticut, United States, 06106
Yale University
New Haven, Connecticut, United States, 06520-8032
United States, Delaware
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
Lee Memorial Health System
Fort Myers, Florida, United States, 33901
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, United States, 32207-8426
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States, 33136
Florida Hospital
Orlando, Florida, United States, 32803
M D Anderson Cancer Center- Orlando
Orlando, Florida, United States, 32806
Nemours Childrens Clinic - Orlando
Orlando, Florida, United States, 32806
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States, 32504
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
Saint Joseph Children's Hospital of Tampa
Tampa, Florida, United States, 33607
United States, Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States, 30322
United States, Hawaii
University of Hawaii
Honolulu, Hawaii, United States, 96813
United States, Illinois
Childrens Memorial Hospital
Chicago, Illinois, United States, 60614
University of Illinois
Chicago, Illinois, United States, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
Saint Jude Midwest Affiliate
Peoria, Illinois, United States, 61602
Southern Illinois University
Springfield, Illinois, United States, 62702
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Louisiana
Tulane University Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
Sinai Hospital of Baltimore
Baltimore, Maryland, United States, 21215
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48202
United States, Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States, 55455
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
The Childrens Mercy Hospital
Kansas City, Missouri, United States, 64108
Saint John's Mercy Medical Center
Saint Louis, Missouri, United States, 63141
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, United States, 68114
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
UMDNJ - Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States, 08903
Overlook Hospital
Summit, New Jersey, United States, 07902
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87106
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Winthrop University Hospital
Mineola, New York, United States, 11501
Columbia University Medical Center
New York, New York, United States, 10032
State University of New York Upstate Medical University
Syracuse, New York, United States, 13210
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Presbyterian Hospital
Charlotte, North Carolina, United States, 28204
Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States, 44106
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
The Children's Medical Center of Dayton
Dayton, Ohio, United States, 45404
Mercy Children's Hospital
Toledo, Ohio, United States, 43608
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
Natalie W Bryant Cancer Center
Tulsa, Oklahoma, United States, 74136
United States, Oregon
Legacy Emanuel Hospital and Health Center
Portland, Oregon, United States, 97227
Legacy Emanuel Children's Hospital
Portland, Oregon, United States, 97227
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, United States, 17033
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States, 19134
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, South Carolina
Palmetto Health Richland
Columbia, South Carolina, United States, 29203
United States, Tennessee
East Tennessee Childrens Hospital
Knoxville, Tennessee, United States, 37916
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
Driscoll Children's Hospital
Corpus Christi, Texas, United States, 78411
Medical City Dallas Hospital
Dallas, Texas, United States, 75230
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Baylor College of Medicine
Houston, Texas, United States, 77030
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229
United States, Vermont
University of Vermont
Burlington, Vermont, United States, 05401
United States, Virginia
Childrens Hospital-King's Daughters
Norfolk, Virginia, United States, 23507
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Carilion Clinic Children's Hospital
Roanoke, Virginia, United States, 24014
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States, 99204
United States, Wisconsin
Saint Vincent Hospital
Green Bay, Wisconsin, United States, 54301
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada, T3B 6A8
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Nova Scotia
IWK Health Centre
Halifax, Nova Scotia, Canada, B3J 3G9
Canada, Ontario
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada, K7L 5P9
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Hospital Sainte-Justine
Montreal, Quebec, Canada, H3T 1C5
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, Canada, H3H 1P3
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Yael Mosse Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01154816     History of Changes
Other Study ID Numbers: ADVL0921, NCI-2011-02051, CDR0000680512, U10CA098543, COG-ADVL0921
Study First Received: June 30, 2010
Last Updated: March 17, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Kidney Neoplasms
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Wilms Tumor
Neuroblastoma
Osteosarcoma
Rhabdomyosarcoma
Neoplasms, Germ Cell and Embryonal
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Hepatoblastoma
Rhabdomyosarcoma, Embryonal
Sarcoma
Sarcoma, Ewing's
Neuroectodermal Tumors, Primitive, Peripheral
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Kidney Diseases
Urologic Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Complex and Mixed

ClinicalTrials.gov processed this record on July 20, 2014