Alisertib in Treating Patients With Advanced or Metastatic Sarcoma
Condition: Myxofibrosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Leiomyosarcoma; Recurrent Liposarcoma; Recurrent Malignant Peripheral Nerve Sheath Tumor; Recurrent Undifferentiated Pleomorphic Sarcoma; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7
MeSH terms: Sarcoma; Leiomyosarcoma; Liposarcoma; Nerve Sheath Neoplasms; Neurofibrosarcoma; Histiocytoma, Malignant Fibrous; Recurrence
Intervention: Alisertib; Laboratory Biomarker Analysis
Intervention description: Given PO; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 72.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well alisertib works in treating patients with sarcoma that
      has spread to other places in the body and usually cannot be cured or controlled with
      treatment (advanced) or has spread to other places in the body (metastatic). Alisertib may
      stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed sarcoma that is
             metastatic and/or locally advanced or locally recurrent and unresectable; confirmation
             of pathologic diagnosis will be performed at the registering site; patients will been
             rolled on one of five cohorts of the study:

               -  Cohort 1: liposarcoma

               -  Cohort 2: leiomyosarcoma (non-uterine)

               -  Cohort 3: undifferentiated sarcoma (including malignant fibrous histiocytoma and
                  myxofibrosarcoma)

               -  Cohort 4: malignant peripheral nerve sheath tumor

               -  Cohort 5: other sarcomas

          -  Patients must have measurable disease per Response Evaluation Criteria in Solid
             Tumors(RECIST) 1.1; note: defined as at least one lesion that can be accurately
             measured in at least one dimension (longest diameter to be recorded for non-nodal
             lesions and short axis for nodal lesions) as >= 2 cm with conventional techniques or
             as >= 1 cm with spiral computed tomography (CT) scan, magnetic resonance imaging
             (MRI), or calipers by clinical exam

          -  Any number of prior therapies is permitted; note: the last dose of systemic therapy
             (including tyrosine kinase inhibitors) must have been given >= 4 weeks prior to
             initiation of study therapy; patients receiving BCNU or mitomycin C must have received
             their last dose of such therapy at least 6 weeks prior to initiation of therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelet count >= 100,000/mcL

          -  Total bilirubin =< 1.5 x institutional upper limit of normal

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
             serum glutamate pyruvate transaminase (alanine aminotransferase [AST]) < 3 x
             institutional upper limit of normal if no liver metastases or < 5 x institutional
             upper limit of normal if liver metastases present

          -  Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance >= 60
             mL/min/1.73m^2 for patients with creatinine levels above institutional normal

          -  Women of childbearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation; should a woman become pregnant or suspect she is
             pregnant while she or her partner is participating in this study, she should inform
             her treating physician immediately; men treated or enrolled on this protocol must also
             agree to use adequate contraception prior to the study, for the duration of study
             participation, and 4 months after completion of MLN8237 administration

          -  Ability to understand and the willingness to sign a written informed consent document

          -  According to current guidelines, patients must be able to take oral medication and to
             maintain a fast as required for approximately one hour before and two hours after
             MLN8237 administration

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier;
             patients who have had radiation therapy to more than 25% of the bone marrow; whole
             pelvic radiation is considered to be over 25%

          -  Patients who are receiving any other investigational agents

          -  Patients with known brain metastases

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to MLN8237 including, but not limited to, established allergic reaction to
             benzodiazepines

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, New York Heart Association (NYHA) class II-IV heart failure, unstable
             angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that
             would limit compliance with study requirements

          -  Pregnant women; note: women of child-bearing potential must have a negative serum or
             urine pregnancy test within 7 days prior to registration; breastfeeding should be
             discontinued if the mother is treated with MLN8237

          -  Leiomyosarcoma of the uterus

          -  Patients known to be human immunodeficiency virus (HIV)-positive on antiretroviral
             therapy

          -  Prior allogeneic bone marrow or organ transplantation

          -  Known history of uncontrolled sleep apnea syndrome and other conditions that could
             result in excessive daytime sleepiness such as severe chronic obstructive pulmonary
             disease, requirement for supplemental oxygen, or any conditions that could result in
             excessive toxicity associated with the benzodiazepine-like effects of MLN8237

          -  Requirement for constant administration of proton pump inhibitor, histamine-2 (H2)
             antagonist, or pancreatic enzymes; note: intermittent uses of antacids or H2
             antagonists are allowed

          -  Inability to swallow oral medication or to maintain a required fast for approximately
             one hour before and two hours after MLN8237 administration or any condition that would
             modify small bowel absorption of oral medications, including malabsorption or
             resection of pancreas or upper bowel

          -  Treatment with clinically significant enzyme inducers, such as the enzyme-inducing
             antiepileptic drugs phenytoin, carbamazepine, oxcarbazepine, primidone or
             phenobarbital, or rifampin, rifabutin, rifapentine, or St. John's wort within 14 days
             prior to the first dose of MLN8237 and during the study