Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia
Condition: 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
MeSH terms: Neoplasms; Leukemia; Sarcoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neuroblastoma; Osteosarcoma; Rhabdomyosarcoma; Sarcoma, Ewing; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Rhabdomyosarcoma, Embryonal; Neuroectodermal Tumors, Primitive, Peripheral; Hepatoblastoma; Kidney Neoplasms; Recurrence
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Alisertib; Laboratory Biomarker Analysis; Pharmacological Study
Intervention type(s): Drug; Other; Other
Intervention description(s): Given orally; Correlative studies; Correlative studies
Other intervention name(s): Aurora A Kinase Inhibitor MLN8237; MLN-8237; MLN8237
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment