HepatoblastomaPhase 2NCT01154816

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

A Phase 2 study testing Alisertib, Laboratory Biomarker Analysis and Pharmacological Study in people with Hepatoblastoma and Previously Treated Childhood Rhabdomyosarcoma, run by Children's Oncology Group at 105 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 1 year to 21 years
Conditions the study is for: Hepatoblastoma, Previously Treated Childhood Rhabdomyosarcoma, Recurrent Childhood Acute Lymphoblastic Leukemia
What is being tested?: Alisertib, Laboratory Biomarker Analysis and Pharmacological Study
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 118 participants
Where: 105 sitesin 2 countries
Study dates: Feb 2011to 30 Jun 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 1 year to 21 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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

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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

Who cannot join

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

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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

Trial locations and contacts

105 sites in 2 countries.

Country

City, postcode or hospital

105 sites in 2 countries

United States97 sites

University of New Mexico Cancer Center
Albuquerque, New Mexico, 87102
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Children's Hospital of Alabama
Birmingham, Alabama, 35233
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of Vermont College of Medicine
Burlington, Vermont, 05405
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
University of Illinois
Chicago, Illinois, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Palmetto Health Richland
Columbia, South Carolina, 29203
Nationwide Children's Hospital
Columbus, Ohio, 43205
Driscoll Children's Hospital
Corpus Christi, Texas, 78411
Medical City Dallas Hospital
Dallas, Texas, 75230
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Dayton Children's Hospital
Dayton, Ohio, 45404
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Southern California Permanente Medical Group
Downey, California, 90242
Lee Memorial Health System
Fort Myers, Florida, 33901
Cook Children's Medical Center
Fort Worth, Texas, 76104
Saint Vincent Hospital
Green Bay, Wisconsin, 54301
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, 17033
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Riley Hospital for Children
Indianapolis, Indiana, 46202
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
The Childrens Mercy Hospital
Kansas City, Missouri, 64108
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806
Children's Hospital Los Angeles
Los Angeles, California, 90027
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Children's Hospital Central California
Madera, California, 93636-8762
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Children¿s Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Winthrop University Hospital
Mineola, New York, 11501
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903
Yale University
New Haven, Connecticut, 06520
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112
Columbia University/Herbert Irving Cancer Center
New York, New York, 10032
Childrens Hospital-King's Daughters
Norfolk, Virginia, 23507
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
Children's Hospital of Orange County
Orange, California, 92868
Florida Hospital Orlando
Orlando, Florida, 32803
Nemours Children's Clinic - Orlando
Orlando, Florida, 32806
UF Cancer Center at Orlando Health
Orlando, Florida, 32806
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Childrens Oncology Group
Philadelphia, Pennsylvania, 19104
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227
Legacy Emanuel Hospital and Health Center
Portland, Oregon, 97227
Oregon Health and Science University
Portland, Oregon, 97239
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298
Carilion Clinic Children's Hospital
Roanoke, Virginia, 24014
Mayo Clinic
Rochester, Minnesota, 55905
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
Rady Children's Hospital - San Diego
San Diego, California, 92123
UCSF Medical Center-Parnassus
San Francisco, California, 94143
Seattle Children's Hospital
Seattle, Washington, 98105
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Washington University School of Medicine
St Louis, Missouri, 63110
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
All Children's Hospital
St. Petersburg, Florida, 33701
Overlook Hospital
Summit, New Jersey, 07902
State University of New York Upstate Medical University
Syracuse, New York, 13210
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467-2490
Mercy Children's Hospital
Toledo, Ohio, 43608
Natalie Warren Bryant Cancer Center at Saint Francis
Tulsa, Oklahoma, 74136
New York Medical College
Valhalla, New York, 10595
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157

Other trials in United States

Canada8 sites

Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, K7L 5P9
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

About this study

Official title: A Phase II Study of MLN8237, a Selective Aurora A Kinase Inhibitor in Children With Recurrent/Refractory Solid Tumors and Leukemias

Read the detailed description

PRIMARY OBJECTIVE:

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:

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).

ARM I (NEUROBLASTOMA- MEASURABLE): 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.

ARM II (NEUROBLASTOMA-MIBG EVALUABLE): 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.

ARM III (RHABDOMYOSARCOMA): 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.

ARM IV (OSTEOSARCOMA): 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.

ARM V (EWING SARCOMA/ PERIPHERAL PNET): 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.

ARM VI (NON-RMS SOFT TISSUE SARCOMA): 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.

ARM VII (HEPATOBLASTOMA): 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.

ARM VIII (MALIGNANT GERM CELL TUMOR): 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.

ARM IX (WILMS TUMOR): 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.

ARM X (ACUTE LYMPHOBLASTIC LEUKEMIA): 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.

ARM XI (ACUTE MYELOGENOUS LEUKEMIA): 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.

ARM XII (RHABDOID MALIGNANCY): 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.

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.

Conditions: Hepatoblastoma, Previously Treated Childhood Rhabdomyosarcoma, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Recurrent Childhood Kidney Neoplasm, Recurrent Childhood Malignant Germ Cell Tumor
Being tested: Alisertib, Laboratory Biomarker Analysis, Pharmacological Study
Medical subject headings: Hepatoblastoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neuroectodermal Tumors, Primitive, Peripheral, Neuroblastoma, Osteosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AlisertibDrug
Also called Aurora A Kinase Inhibitor MLN8237, MLN-8237, MLN8237
Given orally
Laboratory Biomarker AnalysisOther
Correlative studies
Pharmacological StudyOther
Correlative studies

Study groups in NCT01154816
Study group	Role	What they receive
Arm I (neuroblastoma- measurable)	Experimental	Patients with measurable neuroblastoma 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. Receives: Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Arm II (Neuroblastoma- MIBG evaluable)	Experimental	Patients MIBG evaluable neuroblastoma 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. Receives: Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Arm III (rhabdomyosarcoma)	Experimental	Patients with rhabdomyosarcoma 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. Receives: Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Arm IV (osteosarcoma)	Experimental	Patients with osteosarcoma 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. Receives: Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Arm V (Ewing sarcoma/peripheral PNET)	Experimental	Patients with Ewing sarcoma/peripheral PNET 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. Receives: Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Arm VI (non-RMS soft tissue sarcoma)	Experimental	Patients with non-RMS soft tissue sarcoma 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. Receives: Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Arm VII (hepatoblastoma)	Experimental	Patients hepatoblastoma 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. Receives: Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Arm VIII (malignant germ cell tumor)	Experimental	Patients with malignant germ cell tumor 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. Receives: Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Arm IX (Wilms tumor)	Experimental	Patients with Wilms tumor 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. Receives: Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Arm X (acute lymphoblastic leukemia)	Experimental	Patients with acute lymphoblastic leukemia 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. Receives: Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Arm XI (acute myelogenous leukemia)	Experimental	Patients acute myelogenous leukemia 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. Receives: Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Arm XII (rhabdoid malignancy)	Experimental	Patients with rhabdoid malignancy 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. Receives: Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Overall Response
For patients with recurrent solid tumors a patient who experienced a complete or partial response according to RECIST version 1.1 criteria is considered a responder. For patients with recurrent acute lymphoblastic leukemia a patient who experiences a bone marrow evaluation with < 5% blast cells on morphological evaluation of bone marrow will be considered a responder. For patients with recurrent acute myelogenous leukemia a patient who experiences a complete remission or complete remission with partial recovery of platelet count according to the AML International Working Group Criteria will be considered a responder.
Measured: From first dose of alisertib through 6 cycles of protocol therapy or until removal from protocol therapy whichever occurred first.

Secondary outcomes (7)

Number of Patients Cycles With Grade 3 or Higher Adverse Event
The number of patient-cycles in which the adverse event considered grade 3 or higher AE according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 considered by the treating physician to be possibly, probably or definitely related to alisertib.
Measured: Up to 24 months
Serum Concentration of Alisertib Prior to the First Day of Administration
Serum concentration of alisertib prior to the first day of administration in nanograms/milliliter.
Measured: day 1 of protocol therapy
Serum Concentration of Alisertib on the First Day of Administration One Hour After Administration
Serum concentration of alisertib on the first day of administration one hour after administration in nanograms/milliliter.
Measured: day 1 of protocol therapy
Serum Concentration of Alisertib on the First Day of Administration Three Hours After Administration
Serum concentration of alisertib on the first day of administration three hours after administration in nanograms/milliliter.
Measured: day 1 of protocol therapy
Serum Concentration of Alisertib on the First Day of Administration Six Hours After Administration
Serum concentration of alisertib on the first day of administration six hours after administration in nanograms/milliliter.
Measured: day 1 of protocol therapy
Serum Concentration of Alisertib on the Fourth Day of Administration Prior to the Administration of the Day 4 Dose
Serum concentration of alisertib on the fourth day of administration prior to the administration of the day 4 dose in nanograms/milliliter.
Measured: day 4 of protocol therapy
Serum Concentration of Alisertib on the Seventh Day of Administration Prior to the Administration of the Day 7 Dose.
Serum concentration of alisertib on the seventh day of administration prior to the administration of the day 7 dose in nanograms/milliliter.
Measured: day 7 of protocol therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 201130 Jun 2019

First posted1 Jul 2010 (estimated)
Study startFeb 2011
Primary completion31 Dec 2015
Study completion30 Jun 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for HepatoblastomaStudies of the same condition, open and under way.
More trials run by Children's Oncology GroupThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 118 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01154816
Sponsor's protocol ID: ADVL0921
Other IDs: NCI-2011-02051, CDR0000680512, ADVL0921, ADVL0921, U10CA098543
Status last verified: Sep 2017
First submitted: 30 Jun 2010
Last updated: 13 May 2020
Results posted: Yes, on ClinicalTrials.gov

Publications

Zhou X, Mould DR, Yuan Y, Fox E, Greengard E, Faller DV, Venkatakrishnan K. Population Pharmacokinetics and Exposure-Safety Relationships of Alisertib in Children and Adolescents With Advanced Malignancies. J Clin Pharmacol. 2022 Feb;62(2):206-219. doi: 10.1002/jcph.1958. Epub 2022 Jan 15.
PubMed 34435684
Mosse YP, Fox E, Teachey DT, Reid JM, Safgren SL, Carol H, Lock RB, Houghton PJ, Smith MA, Hall D, Barkauskas DA, Krailo M, Voss SD, Berg SL, Blaney SM, Weigel BJ. A Phase II Study of Alisertib in Children with Recurrent/Refractory Solid Tumors or Leukemia: Children's Oncology Group Phase I and Pilot Consortium (ADVL0921). Clin Cancer Res. 2019 Jun 1;25(11):3229-3238. doi: 10.1158/1078-0432.CCR-18-2675. Epub 2019 Feb 18.
PubMed 30777875

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Advanced Malignant Solid Neoplasm, Recurrent Childhood Ependymoma
Active, not recruitingPhase 2
Agnostic Therapy in Rare Solid Tumors
Urachal Cancer, Parathyroid Carcinoma

All Hepatoblastoma trials

Study at a glance

From the registry record, last updated by the sponsor on 13 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II Study of MLN8237, a Selective Aurora A Kinase Inhibitor in Children With Recurrent/Refractory Solid Tumors and Leukemias
ClinicalTrials.gov ID: NCT01154816
Acronym / sponsor ID: ADVL0921
Conditions: Hepatoblastoma, Previously Treated Childhood Rhabdomyosarcoma, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Recurrent Childhood Kidney Neoplasm, Recurrent Childhood Malignant Germ Cell Tumor
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 118 participants (actual)
Lead sponsor: Children's Oncology GroupResearch network
Collaborators: National Cancer Institute (NCI)
Study start: Feb 2011
Primary completion: 31 Dec 2015 (actual)
Study completion: 30 Jun 2019 (actual)
First posted: 1 Jul 2010 (estimated)
Results: Posted 5 Jun 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVE:

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:

To further define and describe the toxicities of MLN8237 administered on this schedule.