Alisertib and Fractionated Stereotactic Radiosurgery in Treating Patients With Recurrent High Grade Gliomas
Condition: Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Tumor
MeSH terms: Glioblastoma; Glioma; Astrocytoma; Ependymoma; Gliosarcoma; Oligodendroglioma; Recurrence
Intervention: Hyperfractionated radiation therapy; Stereotactic radiosurgery; Alisertib; Quality-of-life assessment
Intervention description: Undergo hyperfractionated radiation therapy; Undergo stereotactic radiosurgery; Given PO; Ancillary studies
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase I trial studies the side effects and best dose of alisertib when combined with
      fractionated stereotactic radiosurgery in treating patients with high-grade gliomas that have
      returned after previous treatment with radiation therapy (recurrent). Alisertib may stop the
      growth of tumor cells by blocking an enzyme needed for the cells to divide. Radiation therapy
      uses high energy x rays to kill tumor cells. Stereotactic radiosurgery uses special
      positioning equipment to send a single high dose of radiation directly to the tumor and cause
      less damage to normal tissue. Delivering stereotactic radiosurgery over multiple doses
      (fractionation) may cause more damage to tumor tissue than normal tissue while maintaining
      the advantage of its accuracy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients must have a previously histologically or cytologically confirmed high grade
             glioma (astrocytic or oligodendroglial supratentorial tumors grade 3 or 4) that has
             been previously treated with fractionated radiation therapy and now shows evidence of
             recurrence.

          2. Patients must have recovered from the toxic effects of prior therapy.

          3. Patients must have recovered from the effects of surgery. There must be a minimum of
             21 days from the day of surgery to the day of protocol treatment. For core or needle
             biopsy, a minimum of 7 days must have elapsed prior to the day of protocol treatment.

          4. Prior treatment with cytotoxic and biological agents is permissible. There should be
             at least a 2-week break between prior treatment and the protocol treatment.

          5. Prior treatment with fractionated radiation therapy (up to 60Gy) is an eligibility
             criterion, however there should not have been a second course of fractionated
             radiotherapy to the supratentorial area.

          6. One prior single fraction radiosurgical procedure within the treatment field is
             acceptable if V12<5 cc (V12 is the volume of normal brain (outside GTV) receiving 12
             or more Gy). Additional radiosurgical procedures outside of the treatment area are
             acceptable.

          7. Subject must be able to take oral medication and to maintain a fast, is required for 2
             hours before and 1 hour after MLN8237 administration.

          8. ANC > 1500/mm³, platelets > 100,000/mm³, Hgb > 9 g/dL. Values must be obtained without
             need for myeloid growth factor or platelet transfusion support within 14 days of
             registration. However, erythrocyte growth factor is allowed as per published ASCO
             guidelines.

          9. Total bilirubin ≤ ULN, SGOT (AST) and SGPT (ALT)< 1.5 x ULN, within 14 days of
             registration.

         10. Adequate renal function as defined by: calculated creatinine clearance must be ≥40
             mL/minute (Cockcroft-Gault), within 14 days of registration.

         11. Age >18 years.

         12. ECOG performance status <2 (see Appendix I).

         13. Life expectancy of greater than 2 months.

         14. Women of childbearing potential must have a negative β-HCG pregnancy test documented
             within 7 days prior to registration.

         15. Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             4 months after last dose.

         16. Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. Known history of uncontrolled sleep apnea syndrome and other conditions that could
             result in excessive daytime sleepiness such as severe chronic obstructive pulmonary
             disease requiring supplemental oxygen.

          2. Systemic infection requiring IV antibiotic therapy within 14 days preceding the first
             dose of study drug, or other severe infection.

          3. Myocardial infarction within 6 months prior to enrollment, New York Heart Association
             (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled
             ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active
             conduction system abnormalities. Prior to study entry, any ECG abnormality at
             Screening has to be documented by the investigator as not medically relevant.

          4. Female subject is pregnant or breast-feeding. Confirmation that the subject is not
             pregnant must be established by a negative serum β-human chorionic gonadotropin
             (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not
             required for post-menopausal or surgically sterilized women.

          5. Patient has received other investigational drugs within 14 days before enrollment

          6. Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.

          7. Other severe acute or chronic medical or psychiatric condition, including uncontrolled
             diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement
             for pancreatic enzymes, any condition that would modify small bowel absorption of oral
             medications, or laboratory abnormality that may increase the risk associated with
             study participation or investigational product administration or may interfere with
             the interpretation of study results and, in the judgment of the investigator, would
             make the patient inappropriate for enrollment in this study.

          8. Treatment with clinically significant enzyme inducers, such as the enzyme-inducing
             antiepileptic drugs phenytoin, carbamazepine 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.

          9. Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or
             hepatitis C. Testing is not required in the absence of clinical findings or suspicion.

         10. Patients have a history of any other malignancy from which the patient has been
             disease-free for less than 2 years, with the exception of adequately treated basal or
             squamous cell carcinoma of skin, superficial bladder cancer or carcinoma in situ of
             cervix, AJCC (version 7.0) stage 0 or I breast cancer, AJCC (version 7.0) stage I, or
             II prostate cancer.

         11. Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is
             considered to be over 25%.

         12. Patients who cannot swallow whole tablets (i.e. medication tablets)