Pharmacokinetics (PK) Study of AC480 for Recurrent Glioma

Inclusion Criteria

• •Greater than or equal to 18 years old.
• •Karnofsky Performance Status (KPS) greater than or equal to 60%.
• •Patients must be presenting in first, second or third relapse. Relapse is defined as progression following anti-cancer therapy other than surgery, including non-surgical therapies that are considered standard treatment for high-grade glioma if administered to patients with prior low-grade glioma. Prior therapy must have included external beam radiotherapy.
• •Adequate bone marrow, liver and renal function as assessed by the following:
• •* Hematocrit \> or = to 29%
• •* Absolute neutrophil count (ANC) \> or = to 1,500/mL
• •* Platelet count \> or = to 125,000/mL
• •* Total bilirubin \< or = to 1.5 x ULN
• •* ALT and AST \< or equal to 2.5 x the ULN
• •* INR \< 1.5 or a PT/PTT within normal limits (unless on therapeutic anti-coagulation). Patients receiving anti-coagulation treatment with a low-molecular weight heparin will be allowed to participate, however oral warfarin is not permitted except for low-dose warfarin (1mg po DAILY).
• •* Creatinine \< or = to 1.5 x ULN
• •* Serum Na, K+, Mg2+, Phosphate and Ca2+ Within Normal Limit (WNL)
• •An interval of at least 12 weeks from completion of standard, daily XRT, unless one of the following occurs: a) new area of enhancement on MRI imaging that is outside the XRT field; b) biopsy proven recurrent tumor; c) radiographic evidence of progressive tumor on 2 consecutive scans at least 4 weeks apart.
• •An interval of at least 4 weeks from prior chemotherapy (except nitrosoureas which require 6 weeks) unless there is unequivocal evidence of tumor progression and the patient has recovered from all anticipated toxicities from prior therapy.
• •An interval of a least 4 weeks from exposure to investigational agents, unless there is unequivocal evidence of tumor progression and the patients has recovered from all anticipated toxicities from prior therapy.
• •Signed written informed consent including HIPAA language according to institutional guidelines. This informed consent shall include language whereby Ambit shall have access to the patient's protected health information. A signed informed consent must be obtained prior to any study specific procedures.
• •If sexually active, patients will take contraceptive measures for the duration of the treatments and for 3 months following discontinuation of AC480.
• •Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (sensitivity \< or = to 25IU HCG/L) within 72 hours prior to the start of study drug administration. Males and females age ≥ 18 years. WOCBP include any female that has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not post menopausal (defined as amenorrhea \> 12 consecutive months; or women on hormone replacement therapy \[HRT\] with documented serum follicle stimulating hormone \[FSH\] level \> 35 mIU/mL). Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or are practicing abstinence or where the partner is sterile (e.g., vasectomy), should be considered to be of childbearing potential.
• •Patients having received bevacizumab are eligible four weeks after the last dose of bevacizumab.
• •Drugs (or medical conditions) that are generally accepted to have a risk of causing torsades de pointes (see Appendix E). Subjects who have discontinued any of these medications must have a wash-out period of at least 5 days or 5 half-lives of the drug (whichever is greater) prior to the first dose of AC480.
• •Proton pump inhibitors and histamine H2 antagonists. Other antacid agents may be taken, but not within 8 hours before or 4 hours after dosing of AC480. A detailed log recording administration of other antacids in relation to AC480 must be kept.
• •Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the judgment of the Principal Investigator, could jeopardize subject safety or interfere with the objectives of the study.
• •Patient is \< 3 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ.
• •Concurrent administration of warfarin, rifampin or St. John's Wort, except for low-dose warfarin (1mg po DAILY).
• •Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.