A Phase 2 interventional study of Alisertib and Laboratory Biomarker Analysis in Hepatoblastoma, Previously Treated Childhood Rhabdomyosarcoma and Recurrent Childhood Acute Lymphoblastic Leukemia, sponsored by Children's Oncology Group. Completed at 105 sites in 2 countries. Open to participants aged 1 Year to 21 Years. Per ClinicalTrials.gov, last updated 2020-05-13.
Sponsored by Children's Oncology Group · Phase 2, Interventional, and Treatment
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.
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.
82 studies on the registry are indexed under Hepatoblastoma; 17 are open to participants now.
This study's enrollment of 118 is above the median of 30 across 60 interventional studies indexed under Hepatoblastoma.
Browse Hepatoblastoma studies →Children's Oncology Group is the lead sponsor of 448 studies on the registry; 36 are open to participants now.
Of its 12 completed or terminated interventional studies of FDA-regulated products, 11 (92%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients must have had histologic verification of at original diagnosis or at relapse, to include any of the following malignancies (no other histology is eligible):
Disease status for solid tumor patients:
Note: The following do not qualify as measurable disease:
Disease status for leukemia patients:
Acute lymphoid leukemia:
Acute myeloid leukemia according to FAB classification
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:
Myelosuppressive chemotherapy:
Solid tumors:
Leukemia:
For patients with solid tumors without bone marrow involvement:
For patients with solid tumors and known bone marrow disease:
or radioisotope (GFR) 70 mL/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Alisertib · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study
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.
Drug: Alisertib · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study
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.
Drug: Alisertib · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study
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.
Drug: Alisertib · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study
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.
Drug: Alisertib · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study
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.
Drug: Alisertib · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study
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.
Drug: Alisertib · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study
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.
Drug: Alisertib · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study
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.
Drug: Alisertib · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study
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.
Drug: Alisertib · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study
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.
Drug: Alisertib · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study
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.
Drug: Alisertib · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study
Given orally
Also known as: Aurora A Kinase Inhibitor MLN8237, MLN-8237, MLN8237
Correlative studies
Correlative studies
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.
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
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
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
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
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
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
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
| Milestone | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 20 | 12 | 10 | 10 | 10 | 8 | 6 | 7 | 10 | 10 | 11 | 4 |
| Completed | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Not completed | 20 | 10 | 10 | 10 | 10 | 8 | 6 | 7 | 9 | 10 | 11 | 4 |
| Withdrew: Withdrawal by subject | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 0 |
| Withdrew: Progressive disease | 13 | 8 | 9 | 9 | 8 | 8 | 5 | 6 | 8 | 6 | 10 | 3 |
| Withdrew: Physician decision | 1 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 1 | 1 | 1 |
| Withdrew: Adverse event | 5 | 2 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
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.
| Patients | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Number of Participants With Overall Response | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
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.
| Patient-cycle | All Patients |
|---|---|
| Abdominal Pain | 3 |
| Prolonged Partial Thromboplatin Time | 1 |
| Acute Kidney Injury | 1 |
| Agitation | 1 |
| Alanine Aminotransferase Elevation | 25 |
| Allergic Reaction | 1 |
| Alopecia | 27 |
| Anal Mucocitis | 1 |
| Anemia | 141 |
| Anorexia | 8 |
| Aspartate Aminotransferase Increase | 15 |
| Back Pain | 1 |
| Blood Bilirubin Increase | 7 |
| Blurred Vision | 2 |
| Bullous Dermatitis | 1 |
| Colitis | 2 |
| Confusion | 1 |
| Dehydration | 5 |
| Depression | 1 |
| Diarrhea | 8 |
| Dizziness | 15 |
| Dry Mouth | 1 |
| Enterocolitis | 1 |
| Erectile Dysfunction | 1 |
| Euphoria | 3 |
| Eye Pain | 1 |
| Fatigue | 14 |
| Febrile Neutropenia | 13 |
| Other Gastrointestinal Disorders | 1 |
| GGT Increase | 2 |
| Headache | 3 |
| Hepatic Hemhorrage | 1 |
| Hyperkalemia | 1 |
| Hypersomnia | 1 |
| Hyperuricemia | 1 |
| Hypoalbuminemia | 7 |
| Hypocalcemia | 2 |
| Hypokalemia | 9 |
| Hyponatremia | 3 |
| Hypophosphatemia | 1 |
| Other Infections | 1 |
| INR Increase | 1 |
| Keratitis | 1 |
| Lethargy | 1 |
| Lung Infection | 1 |
| Lymphocyte Count Decrease | 65 |
| Lymphocyte Count Increase | 1 |
| Mucosal Infection | 2 |
| Oral Mucocitis | 35 |
| Nausea | 11 |
| Decreased Neutrophil Count | 208 |
| Oral Pain | 12 |
| Otitis Media | 1 |
| Pain in an Extremity | 1 |
| Palmar-Plantar Erythrodysesthesia Syndrome | 10 |
| Photophobia | 4 |
| Platelet Count Decrease | 92 |
| Pruritis | 4 |
| Psychiatric Disorders | 1 |
| Respiratory Failure | 1 |
| Serum Amylase Increase | 1 |
| Skin Infection | 1 |
| Somnolence | 2 |
| Sore Throat | 1 |
| Tumor Lysis Syndrome | 1 |
| Upper Respiratory Infection | 1 |
| Urticaria | 1 |
| Urinary Tract Infection | 4 |
| Vomiting | 1 |
| White Blood Cell Decrease | 163 |
Serum concentration of alisertib prior to the first day of administration in nanograms/milliliter.
| ng/ml | All Patients |
|---|---|
| Serum Concentration of Alisertib Prior to the First Day of Administration | 0 ± 0 |
Serum concentration of alisertib on the first day of administration one hour after administration in nanograms/milliliter.
| ng/ml | All Patients |
|---|---|
| Serum Concentration of Alisertib on the First Day of Administration One Hour After Administration | 1874.0625 ± 1131.87375 |
Serum concentration of alisertib on the first day of administration three hours after administration in nanograms/milliliter.
| ng/ml | All Patients |
|---|---|
| Serum Concentration of Alisertib on the First Day of Administration Three Hours After Administration | 1863.9375 ± 588.116822 |
Serum concentration of alisertib on the first day of administration six hours after administration in nanograms/milliliter.
| ng/ml | All Patients |
|---|---|
| Serum Concentration of Alisertib on the First Day of Administration Six Hours After Administration | 1234 ± 512.203475 |
Serum concentration of alisertib on the fourth day of administration prior to the administration of the day 4 dose in nanograms/milliliter.
| ng/ml | All Patients |
|---|---|
| Serum Concentration of Alisertib on the Fourth Day of Administration Prior to the Administration of the Day 4 Dose | 1123.73333 ± 715.013235 |
Serum concentration of alisertib on the seventh day of administration prior to the administration of the day 7 dose in nanograms/milliliter.
| ng/ml | All Patients |
|---|---|
| Serum Concentration of Alisertib on the Seventh Day of Administration Prior to the Administration of the Day 7 Dose. | 1097.50645 ± 1012.34016 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Recurrent Neuroblastoma With Measurable Disease at Enrollment | — | 7/20 (35%) | 15/20 (75%) |
| Recurrent Neuroblastoma Only MIBG Evaluable Disease at Enroll | — | 5/12 (41.7%) | 11/12 (91.7%) |
| Previously Treated Childhood Rhabdomyosarcoma | — | 4/10 (40%) | 8/10 (80%) |
| Recurrent Osteosarcoma | — | 7/10 (70%) | 9/10 (90%) |
| Recurrent Ewing Sarcoma /Peripheral Neuroectodermal Tumor | — | 5/10 (50%) | 9/10 (90%) |
| Recurrent Childhood Soft Tissue Sarcoma | — | 3/8 (37.5%) | 6/8 (75%) |
| Childhood Hepatoblastoma | — | 6/6 (100%) | 3/6 (50%) |
| Recurrent Childhood Germ Cell Tumor | — | 1/7 (14.3%) | 5/7 (71.4%) |
| Recurrent Wilms Tumor and Other Childhood Kidney Tumors | — | 3/10 (30%) | 9/10 (90%) |
| Recurrent Childhood Acute Lympohblastic Leukemia | — | 8/10 (80%) | 10/10 (100%) |
| Recurrent Childhood Acute Myeloid Leukemia | — | 5/11 (45.5%) | 9/11 (81.8%) |
| Rhaboid Malignancy | — | 2/4 (50%) | 2/4 (50%) |
| Event | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Febrile neutropeniaBlood and lymphatic system disorders | 1/20 | 1/12 | 0/10 | 1/10 | 0/10 | 0/8 | 1/6 | 0/7 | 0/10 | 5/10 | 4/11 | 0/4 |
| HypoalbuminemiaMetabolism and nutrition disorders | 0/20 | 0/12 | 1/10 | 3/10 | 0/10 | 0/8 | 0/6 | 0/7 | 0/10 | 1/10 | 0/11 | 1/4 |
| Gastrointestinal disorders - Other, specifyGastrointestinal disorders | 0/20 | 0/12 | 0/10 | 0/10 | 0/10 | 0/8 | 0/6 | 0/7 | 0/10 | 0/10 | 0/11 | 1/4 |
| HypocalcemiaMetabolism and nutrition disorders | 1/20 | 0/12 | 0/10 | 0/10 | 0/10 | 0/8 | 0/6 | 0/7 | 1/10 | 0/10 | 0/11 | 1/4 |
| HypokalemiaMetabolism and nutrition disorders | 0/20 | 0/12 | 0/10 | 0/10 | 0/10 | 0/8 | 0/6 | 0/7 | 0/10 | 2/10 | 1/11 | 1/4 |
| HyponatremiaMetabolism and nutrition disorders | 0/20 | 0/12 | 0/10 | 1/10 | 1/10 | 0/8 | 1/6 | 0/7 | 0/10 | 1/10 | 0/11 | 1/4 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 1/20 | 0/12 | 0/10 | 1/10 | 0/10 | 0/8 | 0/6 | 0/7 | 0/10 | 0/10 | 0/11 | 1/4 |
| KeratitisEye disorders | 0/20 | 0/12 | 0/10 | 0/10 | 0/10 | 0/8 | 0/6 | 0/7 | 0/10 | 0/10 | 0/11 | 1/4 |
| Mucositis oralGastrointestinal disorders | 3/20 | 1/12 | 0/10 | 2/10 | 0/10 | 0/8 | 0/6 | 0/7 | 1/10 | 2/10 | 0/11 | 0/4 |
| Skin infectionInfections and infestations | 0/20 | 0/12 | 0/10 | 0/10 | 2/10 | 0/8 | 0/6 | 0/7 | 0/10 | 0/10 | 0/11 | 0/4 |
| Event | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Neutrophil count decreasedInvestigations | 15/20 | 10/12 | 6/10 | 7/10 | 4/10 | 1/8 | 2/6 | 4/7 | 7/10 | 2/10 | 6/11 | 2/4 |
| AnemiaBlood and lymphatic system disorders | 9/20 | 7/12 | 5/10 | 5/10 | 3/10 | 1/8 | 2/6 | 1/7 | 6/10 | 7/10 | 7/11 | 2/4 |
| Platelet count decreasedInvestigations | 11/20 | 5/12 | 4/10 | 4/10 | 3/10 | 1/8 | 2/6 | 2/7 | 5/10 | 7/10 | 6/11 | 1/4 |
| White blood cell decreasedInvestigations | 13/20 | 8/12 | 5/10 | 7/10 | 7/10 | 0/8 | 2/6 | 4/7 | 6/10 | 4/10 | 4/11 | 2/4 |
| Lymphocyte count decreasedInvestigations | 10/20 | 4/12 | 3/10 | 5/10 | 5/10 | 3/8 | 1/6 | 1/7 | 2/10 | 4/10 | 4/11 | 0/4 |
| HypokalemiaMetabolism and nutrition disorders | 1/20 | 1/12 | 2/10 | 1/10 | 1/10 | 0/8 | 1/6 | 0/7 | 0/10 | 4/10 | 0/11 | 0/4 |
| Aspartate aminotransferase increasedInvestigations | 3/20 | 2/12 | 0/10 | 0/10 | 1/10 | 0/8 | 2/6 | 0/7 | 0/10 | 2/10 | 0/11 | 0/4 |
| Mucositis oralGastrointestinal disorders | 3/20 | 4/12 | 3/10 | 1/10 | 3/10 | 1/8 | 1/6 | 1/7 | 2/10 | 1/10 | 3/11 | 0/4 |
| Upper respiratory infectionInfections and infestations | 0/20 | 1/12 | 0/10 | 0/10 | 0/10 | 0/8 | 2/6 | 0/7 | 0/10 | 0/10 | 0/11 | 0/4 |
| AlopeciaSkin and subcutaneous tissue disorders | 6/20 | 1/12 | 2/10 | 1/10 | 3/10 | 0/8 | 0/6 | 2/7 | 0/10 | 0/10 | 0/11 | 1/4 |
| Age, Continuous(Years) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Median | 8 (3 to 20) | 8 (5 to 17) | 12 (4 to 21) | 17 (12 to 21) | 14 (6 to 20) | 16 (13 to 21) | 5 (3 to 14) | 11 (3 to 19) | 10 (3 to 18) | 13 (7 to 19) | 10 (3 to 15) | 5 (2 to 7) | 11 (2 to 21) |
| Sex: Female, Male(Participants) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Female | 10 | 2 | 7 | 3 | 3 | 4 | 1 | 4 | 7 | 3 | 6 | 2 | 52 |
| Male | 10 | 10 | 3 | 7 | 7 | 4 | 5 | 3 | 3 | 7 | 5 | 2 | 66 |
| Ethnicity (NIH/OMB)(Participants) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 3 | 1 | 1 | 3 | 1 | 2 | 3 | 2 | 4 | 2 | 4 | 1 | 27 |
| Not Hispanic or Latino | 15 | 10 | 7 | 7 | 8 | 5 | 3 | 4 | 5 | 8 | 5 | 3 | 80 |
| Unknown or Not Reported | 2 | 1 | 2 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 2 | 0 | 11 |
| Race (NIH/OMB)(Participants) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 2 | 1 | 1 | 2 | 0 | 1 | 1 | 0 | 2 | 2 | 2 | 0 | 14 |
| White | 15 | 7 | 7 | 7 | 8 | 3 | 3 | 4 | 5 | 5 | 2 | 3 | 69 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 3 | 4 | 2 | 1 | 2 | 4 | 2 | 3 | 3 | 3 | 7 | 1 | 35 |
| Region of Enrollment(participants) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Canada | 1 | 2 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 8 |
| United States | 18 | 9 | 9 | 10 | 10 | 8 | 5 | 6 | 8 | 10 | 10 | 4 | 107 |
| United Kingdom | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
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The record gives a start of Feb 2011, a primary completion of Dec 2015 and a completion of Jun 2019. It does not say whether these dates are actual or estimated.
Results were first posted in Jun 2017, 1 year 5 months after primary completion.
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This study is completed, as verified in Sep 2017. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: MLN 8237