Phase I Study of Alisertib With Concurrent Fractionated Stereotactic Radiation Treatment for Recurrent High Grade Gliomas
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.
• 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.
• Patients must have recovered from the toxic effects of prior therapy.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Total bilirubin ≤ ULN, SGOT (AST) and SGPT (ALT)\< 1.5 x ULN, within 14 days of registration.
⁃ Adequate renal function as defined by: calculated creatinine clearance must be ≥40 mL/minute (Cockcroft-Gault), within 14 days of registration.
⁃ Age \>18 years.
⁃ ECOG performance status \<2 (see Appendix I).
⁃ Life expectancy of greater than 2 months.
⁃ Women of childbearing potential must have a negative β-HCG pregnancy test documented within 7 days prior to registration.
⁃ 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.
⁃ Ability to understand and the willingness to sign a written informed consent document.