Alisertib in Treating Patients With Recurrent or Persistent Leiomyosarcoma of the Uterus
Condition: Recurrent Uterine Corpus Sarcoma; Uterine Corpus Leiomyosarcoma
MeSH terms: Leiomyosarcoma; 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: 23.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well alisertib works in treating patients with leiomyosarcoma
      of the uterus that has come back or persistent. 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 incurable recurrent or persistent uterine leiomyosarcoma;
             histologic confirmation of the original primary tumor is required

          -  Patients must have measurable disease; measurable disease is defined by Response
             Evaluation Criteria in Solid Tumors (RECIST) (version 1.1); measurable disease is
             defined as at least one lesion that can be accurately measured in at least one
             dimension (longest diameter to be recorded); each lesion must be >= 10 mm when
             measured by computed tomography (CT), magnetic resonance imaging (MRI), or caliper
             measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes
             must be >= 15 mm in short axis when measured by CT or MRI

          -  Patients must have at least one "target lesion" to be used to assess response on this
             protocol as defined by RECIST version 1.1; tumors within a previously irradiated field
             will be designated as "non-target" lesions unless progression is documented or a
             biopsy is obtained to confirm persistence at least 90 days following completion of
             radiation therapy

          -  Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG)
             protocol, if one exists; in general, this would refer to any active GOG phase III
             protocol for the same patient population (12/10/2012)

          -  Patients who have received one prior regimen must have a GOG performance status of 0,
             1, or 2; patients who have received two prior regimens must have a GOG performance
             status of 0 or 1

          -  Patients should be free of active infection requiring antibiotics (with the exception
             of uncomplicated urinary tract infection [UTI])

          -  Any hormonal therapy directed at the malignant tumor must be discontinued at least one
             week prior to registration

          -  Any other prior therapy directed at the malignant tumor, including chemotherapy and
             immunologic agents, must be discontinued at least three weeks prior to registration
             (12/10/2012)

          -  Any prior radiation therapy must be discontinued at least four weeks prior to
             registration (12/10/2012)

          -  Patients must have had at least one prior chemotherapeutic regimen for management of
             leiomyosarcoma

          -  Patients are allowed to receive, but are not required to receive, one additional
             cytotoxic regimen for management of recurrent or persistent disease (12/10/2012)

          -  Patients must NOT have received any prior therapy directed at Aurora kinase for
             management of recurrent or persistent disease; patients who were treated on GOG-0250
             (gemcitabine + docetaxel plus bevacizumab vs placebo) are eligible; treatment on
             GOG-0250 would count as ONE prior regimen

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Serum creatinine =< institutional upper limit of normal (ULN) OR creatinine clearance
             >= 60 mL/min/1.73m^2 (calculated or measured)

          -  Bilirubin =< ULN

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN

          -  Alkaline phosphatase =< 2.5 x ULN

          -  Patients must have signed an approved informed consent and authorization permitting
             release of personal health information

          -  Patients of childbearing potential must have a negative serum pregnancy test prior to
             the study entry and be practicing an effective form of contraception; pregnant women
             are excluded from this study

          -  Patients must be able to take oral medication and to maintain a fast for 2 hours
             before and 1 hour after MLN8237 administration

          -  Patient must not have taken agents that effect gastric pH within 4 days (any proton
             pump inhibitor), or 1 day (any histamine-2 antagonist) of the planned start of
             therapy; patients must be able to avoid all other types of antacids for 2 hours before
             and 2 hours after each dose of MLN8237

        Exclusion Criteria:

          -  Patients who have had prior therapy with MLN8237 or taken part in a study of an
             investigational compound or device within 4 weeks of entering this study

          -  Patients who have had surgery (excluding biopsy), radiotherapy, or chemotherapy within
             4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to the planned start of
             protocol treatment or those who have not recovered from adverse events due to agents
             administered more than 4 weeks earlier; patients who have had hormonal agents within 1
             week of the planned start of protocol treatment

          -  Patients with other invasive malignancies, with the exception of non-melanoma skin
             cancer, carcinoma in situ of the cervix, or ductal carcinoma in situ of the breast,
             are excluded if there is any evidence of other malignancy being present within the
             last three years

          -  Patients who have received prior radiotherapy to any portion of the abdominal cavity
             or pelvis OTHER THAN for the treatment of uterine leiomyosarcoma within the last three
             years are excluded; thus, patients with a history of prior pelvic radiation for
             uterine leiomyosarcoma are eligible; prior radiation for localized cancer of the
             breast, head and neck, or skin is permitted, provided that it was completed more than
             three years prior to registration, and the patient remains free of recurrent or
             metastatic disease

          -  Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER
             THAN for the treatment of uterine leiomyosarcoma within the last three years are
             excluded; patients may have received prior adjuvant chemotherapy for localized breast
             cancer, provided that it was completed more than three years prior to registration,
             and that the patient remains free of recurrent or metastatic disease

          -  Patients who are nursing because there is an unknown but potential risk for adverse
             events in nursing infants from MLN8237

          -  Patients with a history of central nervous system metastases and/or carcinomatous
             meningitis

          -  Patients with a 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

          -  Patients who are known to be human immunodeficiency virus (HIV) positive

          -  Patients who have had prior allogeneic bone marrow or organ transplantation

          -  Patients with a 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

          -  Patients who require constant administration of proton pump inhibitor, H2 antagonist,
             or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are allowed

          -  Patients who are unable to swallow oral medication or to maintain a fast as required
             for 2 hours before and 1 hour after MLN8237 administration or any condition that would
             modify small bowel absorption of oral medications, including malabsorption, or
             resection of pancreas or upper bowel

          -  Patients who have had 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

          -  Patients who have had a myocardial infarction within 6 months prior to enrollment or
             have New York Heart Association (NYHA) class III (marked limitation of physical
             activity, comfortable at rest, but less than ordinary activity causes fatigue,
             palpitation, or dyspnea) or IV (unable to carry out any physical activity without
             discomfort, symptoms of cardiac insufficiency at rest, if any physical activity is
             undertaken, discomfort is increased) heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities; prior to study entry, any
             electrocardiogram (ECG) abnormality at screening has to be documented by the
             investigator as not medically relevant

          -  Patients must limit alcohol consumption to no more than 1 standard unit of alcohol (12
             oz beer [350 mL], 1.5 oz [45 mL] of 80-proof alcohol, or one 6-oz [175 mL] glass of
             wine) per day during the study and for 30 days from the last dose of MLN8237; patients
             who are unable to comply with these restrictions are not eligible