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, Recurrent Childhood Rhabdomyosarcoma, Recurrent Childhood Soft Tissue Sarcoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Neuroblastoma, Recurrent Osteosarcoma
Conditions
Brief 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.
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). 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.
Interventions
DRUGAlisertib
Given orally
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERPharmacological Study
Correlative studies
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Response | From first dose of alisertib through 6 cycles of protocol therapy or until removal from protocol therapy whichever occurred first. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Concentration of Alisertib Prior to the First Day of Administration | day 1 of protocol therapy | Serum concentration of alisertib prior to the first day of administration in nanograms/milliliter. |
| Serum Concentration of Alisertib on the First Day of Administration One Hour After Administration | day 1 of protocol therapy | Serum concentration of alisertib on the first day of administration one hour after administration in nanograms/milliliter. |
| Serum Concentration of Alisertib on the First Day of Administration Three Hours After Administration | day 1 of protocol therapy | Serum concentration of alisertib on the first day of administration three hours after administration in nanograms/milliliter. |
| Number of Patients Cycles With Grade 3 or Higher Adverse Event | Up to 24 months | 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. |
| Serum Concentration of Alisertib on the Fourth Day of Administration Prior to the Administration of the Day 4 Dose | day 4 of protocol therapy | Serum concentration of alisertib on the fourth day of administration prior to the administration of the day 4 dose in nanograms/milliliter. |
| Serum Concentration of Alisertib on the Seventh Day of Administration Prior to the Administration of the Day 7 Dose. | day 7 of protocol therapy | Serum concentration of alisertib on the seventh day of administration prior to the administration of the day 7 dose in nanograms/milliliter. |
| Serum Concentration of Alisertib on the First Day of Administration Six Hours After Administration | day 1 of protocol therapy | Serum concentration of alisertib on the first day of administration six hours after administration in nanograms/milliliter. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Recurrent Neuroblastoma With Measurable Disease at Enrollment Experimental: Arm 1 | 20 |
| Recurrent Neuroblastoma Only MIBG Evaluable Disease at Enroll Experimental: Arm 2 | 12 |
| Previously Treated Childhood Rhabdomyosarcoma Experimental: Arm 3 | 10 |
| Recurrent Osteosarcoma Experimental: Arm 4 | 10 |
| Recurrent Ewing Sarcoma /Peripheral Neuroectodermal Tumor Experimental: Arm 5 | 10 |
| Recurrent Childhood Soft Tissue Sarcoma Experimental: Arm 6 | 8 |
| Childhood Hepatoblastoma Experimental: Arm 7 | 6 |
| Recurrent Childhood Germ Cell Tumor Experimental: Arm 8 | 7 |
| Recurrent Wilms Tumor and Other Childhood Kidney Tumors Experimental: Arm 9 | 10 |
| Recurrent Childhood Acute Lympohblastic Leukemia Experimental: Arm 10 | 10 |
| Recurrent Childhood Acute Myeloid Leukemia Experimental: Arm 11 | 11 |
| Rhaboid Malignancy Experimental: Arm 12 | 4 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 1 | 1 | 1 |
| Overall Study | Progressive Disease | 13 | 8 | 9 | 9 | 8 | 8 | 5 | 6 | 8 | 6 | 10 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Recurrent Neuroblastoma With Measurable Disease at Enrollment | Recurrent Neuroblastoma Only MIBG Evaluable Disease at Enroll | Previously Treated Childhood Rhabdomyosarcoma | Recurrent Osteosarcoma | Recurrent Ewing Sarcoma /Peripheral Neuroectodermal Tumor | Recurrent Childhood Soft Tissue Sarcoma | Childhood Hepatoblastoma | Recurrent Childhood Germ Cell Tumor | Recurrent Wilms Tumor and Other Childhood Kidney Tumors | Recurrent Childhood Acute Lympohblastic Leukemia | Recurrent Childhood Acute Myeloid Leukemia | Rhaboid Malignancy | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 8 Years | 8 Years | 12 Years | 17 Years | 14 Years | 16 Years | 5 Years | 11 Years | 10 Years | 13 Years | 10 Years | 5 Years | 11 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 2 Participants | 4 Participants | 1 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 10 Participants | 7 Participants | 7 Participants | 8 Participants | 5 Participants | 3 Participants | 4 Participants | 5 Participants | 8 Participants | 5 Participants | 3 Participants | 80 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 2 Participants | 1 Participants | 2 Participants | 4 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 7 Participants | 1 Participants | 35 Participants |
| Race (NIH/OMB) White | 15 Participants | 7 Participants | 7 Participants | 7 Participants | 8 Participants | 3 Participants | 3 Participants | 4 Participants | 5 Participants | 5 Participants | 2 Participants | 3 Participants | 69 Participants |
| Region of Enrollment Canada | 1 participants | 2 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 1 participants | 0 participants | 1 participants | 0 participants | 8 participants |
| Region of Enrollment United Kingdom | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Region of Enrollment United States | 18 participants | 9 participants | 9 participants | 10 participants | 10 participants | 8 participants | 5 participants | 6 participants | 8 participants | 10 participants | 10 participants | 4 participants | 107 participants |
| Sex: Female, Male Female | 10 Participants | 2 Participants | 7 Participants | 3 Participants | 3 Participants | 4 Participants | 1 Participants | 4 Participants | 7 Participants | 3 Participants | 6 Participants | 2 Participants | 52 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 3 Participants | 7 Participants | 7 Participants | 4 Participants | 5 Participants | 3 Participants | 3 Participants | 7 Participants | 5 Participants | 2 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 20 | 11 / 12 | 8 / 10 | 9 / 10 | 9 / 10 | 6 / 8 | 3 / 6 | 5 / 7 | 9 / 10 | 10 / 10 | 9 / 11 | 2 / 4 |
| serious Total, serious adverse events | 7 / 20 | 5 / 12 | 4 / 10 | 7 / 10 | 5 / 10 | 3 / 8 | 6 / 6 | 1 / 7 | 3 / 10 | 8 / 10 | 5 / 11 | 2 / 4 |
Outcome results
Primary
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.
Time frame: From first dose of alisertib through 6 cycles of protocol therapy or until removal from protocol therapy whichever occurred first.
Population: Of the 118 enrolled patients, two were not evaluable for the primary outcome measure. Neither received protocol therapy. One was enrolled in arm 11, one was enrolled in Arm 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Participants With Overall Response | 0 Patients |
| Recurrent Neuroblastoma Only MIBG Evaluable Disease at Enroll | Number of Participants With Overall Response | 1 Patients |
| Previously Treated Childhood Rhabdomyosarcoma | Number of Participants With Overall Response | 0 Patients |
| Recurrent Osteosarcoma | Number of Participants With Overall Response | 0 Patients |
| Recurrent Ewing Sarcoma /Peripheral Neuroectodermal Tumor | Number of Participants With Overall Response | 0 Patients |
| Recurrent Childhood Soft Tissue Sarcoma | Number of Participants With Overall Response | 0 Patients |
| Childhood Hepatoblastoma | Number of Participants With Overall Response | 0 Patients |
| Recurrent Childhood Germ Cell Tumor | Number of Participants With Overall Response | 0 Patients |
| Recurrent Wilms Tumor and Other Childhood Kidney Tumors | Number of Participants With Overall Response | 1 Patients |
| Recurrent Childhood Acute Lympohblastic Leukemia | Number of Participants With Overall Response | 0 Patients |
| Recurrent Childhood Acute Myeloid Leukemia | Number of Participants With Overall Response | 0 Patients |
| Rhaboid Malignancy | Number of Participants With Overall Response | 0 Patients |
Secondary
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.
Time frame: Up to 24 months
Population: 116 patients contributed 360 patient-cycles to the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | White Blood Cell Decrease | 163 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Abdominal Pain | 3 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Prolonged Partial Thromboplatin Time | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Acute Kidney Injury | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Agitation | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Alanine Aminotransferase Elevation | 25 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Allergic Reaction | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Alopecia | 27 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Anal Mucocitis | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Anemia | 141 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Anorexia | 8 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Aspartate Aminotransferase Increase | 15 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Back Pain | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Blood Bilirubin Increase | 7 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Blurred Vision | 2 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Bullous Dermatitis | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Colitis | 2 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Confusion | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Dehydration | 5 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Depression | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Diarrhea | 8 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Dizziness | 15 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Dry Mouth | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Enterocolitis | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Erectile Dysfunction | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Euphoria | 3 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Eye Pain | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Fatigue | 14 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Febrile Neutropenia | 13 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Other Gastrointestinal Disorders | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | GGT Increase | 2 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Headache | 3 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Hepatic Hemhorrage | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Hyperkalemia | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Hypersomnia | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Hyperuricemia | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Hypoalbuminemia | 7 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Hypocalcemia | 2 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Hypokalemia | 9 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Hyponatremia | 3 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Hypophosphatemia | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Other Infections | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | INR Increase | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Keratitis | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Lethargy | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Lung Infection | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Lymphocyte Count Decrease | 65 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Lymphocyte Count Increase | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Mucosal Infection | 2 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Oral Mucocitis | 35 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Nausea | 11 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Decreased Neutrophil Count | 208 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Oral Pain | 12 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Otitis Media | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Pain in an Extremity | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Palmar-Plantar Erythrodysesthesia Syndrome | 10 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Photophobia | 4 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Platelet Count Decrease | 92 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Pruritis | 4 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Psychiatric Disorders | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Respiratory Failure | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Serum Amylase Increase | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Skin Infection | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Somnolence | 2 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Sore Throat | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Tumor Lysis Syndrome | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Upper Respiratory Infection | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Urticaria | 1 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Urinary Tract Infection | 4 Patient-cycle |
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Number of Patients Cycles With Grade 3 or Higher Adverse Event | Vomiting | 1 Patient-cycle |
Secondary
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.
Time frame: day 1 of protocol therapy
Population: Of all eligible patients enrolled, 16 provided a first day of administration one hour after administration infusion sample for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Serum Concentration of Alisertib on the First Day of Administration One Hour After Administration | 1874.0625 ng/ml | Standard Deviation 1131.87375 |
Secondary
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.
Time frame: day 1 of protocol therapy
Population: Of all eligible patients enrolled, 16 provided a first day of administration six hours after administration sample for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Serum Concentration of Alisertib on the First Day of Administration Six Hours After Administration | 1234 ng/ml | Standard Deviation 512.203475 |
Secondary
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.
Time frame: day 1 of protocol therapy
Population: Of all eligible patients enrolled, 16 provided a first day of administration three hours after administration sample for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Serum Concentration of Alisertib on the First Day of Administration Three Hours After Administration | 1863.9375 ng/ml | Standard Deviation 588.116822 |
Secondary
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.
Time frame: day 4 of protocol therapy
Population: Of all eligible patients enrolled, 30 provided a fourth day of administration prior to the administration of the day 4 dose sample for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Serum Concentration of Alisertib on the Fourth Day of Administration Prior to the Administration of the Day 4 Dose | 1123.73333 ng/ml | Standard Deviation 715.013235 |
Secondary
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.
Time frame: day 7 of protocol therapy
Population: Of all eligible patients enrolled, 31 provided a seventh day of administration prior to the administration of the day 7 dose sample for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Serum Concentration of Alisertib on the Seventh Day of Administration Prior to the Administration of the Day 7 Dose. | 1097.50645 ng/ml | Standard Deviation 1012.34016 |
Secondary
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.
Time frame: day 1 of protocol therapy
Population: Of all eligible patients enrolled, 32 provided a prior to the first day of administration sample for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | Serum Concentration of Alisertib Prior to the First Day of Administration | 0 ng/ml | Standard Deviation 0 |