Plerixafor and Bevacizumab in Treating Patients with Recurrent High-Grade Glioma

Inclusion Criteria

• Patients must have a histologic diagnosis of glioblastoma (GBM), gliosarcoma, anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), or anaplastic mixed oligoastrocytoma (AOA); patients are eligible if the original histology was lower-grade glioma
• Patients must have an unequivocal progression by magnetic resonance imaging (MRI) or computed tomography (CT) scan; a scan must be performed within 14 days prior to registration and on a steroid dose that has been stable or decreasing for at least 5 days; if the steroid dose is increased between the date of imaging and first dose of plerixafor, a new baseline MRI/CT is required; the same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement; a patient who develops a contraindication to undergo an MRI scan during study treatment may remain on study and undergo contrast enhanced CT scans
• For patients enrolled in Part 2 (surgical substudy), CT or MRI should be performed ideally within 14 days prior to study registration, but because the screening MRI for this subset of subjects will not be used for evaluation of response, it is acceptable for this MRI/CT to have been performed greater than 14 days prior to registration if unavoidable; furthermore, for this same reason, fluctuation in corticosteroid dose around this MRI does not warrant repeat scan so long as there is documented unequivocal evidence of tumor progression available
• Patients with recurrence who undergo resection and are left without measurable or evaluable disease are eligible
• Patients must have recurrent disease and may have had any number of prior relapses (including no prior relapses) on NON-anti-vascular endothelial growth factor (VEGF)(receptor [R]) containing regimens; relapse is defined as progression following initial therapy; for patients who progressed on a prior anti-VEGF(R) containing regimen including bevacizumab, only one prior relapse on an anti-VEGF(R) containing regimen is allowed
• Karnofsky performance status (KPS) >= 60
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin less than institutional upper limit of normal; NOTE: patients with a diagnosis or history of Gilberts will be eligible
• Aspartate aminotransferase (AST) (serum glutamic oxalo-acetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
• Creatinine less than institutional upper limit of normal or creatinine clearance >= 60 mL/min/1.73 m^2 for subjects with creatinine levels above the institutional normal
• Protocol treatment must begin within 5 consecutive days after registration
• For patients enrolled in Part 2 (surgical substudy), patients must be willing to undergo surgical resection and have pre-treatment archival tumor tissue (15 unstained paraffin slides) available for molecular analysis
• Women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours before the start of the investigational product; in addition, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for a minimum of 4 month following last plerixafor dose and 6 months following last bevacizumab dose * Effective birth control includes: ** Birth control pills, depot progesterone, or an intrauterine device plus one barrier method ** Or 2 barrier methods * Effective barrier methods are male and female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm) * Hormonal contraceptive methods are not sufficient, as information about any interaction of plerixafor with hormonal contraceptives is not known * Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients who have had prior chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C); patients must be off treatment with temozolomide for at least 23 days; patients who received non-cytotoxic drug therapy must be off treatment for at least 2 weeks; for patients enrolling in Part 1 or Part 3 AND who have progressed on a prior bevacizumab-containing regimen, patients may continue treatment with bevacizumab 10 mg/kg monotherapy, with last dose of bevacizumab administered no fewer than 14 days from start of plerixafor and bevacizumab; for participants enrolling in Part 1 or Part 3 AND who have progressed on a prior anti-VEGF(R) (other than bevacizumab) containing regimen, patients must be off anti-VEGF(R) treatment for at least 28 days before receiving plerixafor and bevacizumab; for patients enrolled in Part 2 (surgical substudy) AND who have progressed on a prior bevacizumab or other anti-VEGF(R) containing regimen, patients must be off anti-VEGF(R) treatment for at least 28 days prior to surgery; NOTE: participants must have recovered to a grade 0 or 1 from the toxic effects of prior therapy (with the exception of lymphopenia, which is common after therapy with temozolomide); for any patient who received prior bevacizumab or an anti-VEGF(R) therapy, patient must NOT have discontinued that treatment regimen due to a treatment-related toxicity
• Patients must not have received prior Gliadel wafers
• In order to prevent registering patients with pseudo progression rather than true disease progression, patients must not have received any form of cranial radiation within 12 weeks of study entry; NOTE: patients who have received cranial radiation within 12 weeks of study entry will be allowed to register to trial only if either progressive disease is confirmed via biopsy or there is a new area of enhancement consistent with recurrent tumor outside the radiation field (defined as the region outside the high-dose region or 80% isodose line)
• Major surgical procedure (including craniotomy) or significant traumatic injury less than 28 days or those who receive minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 7 days
• Patients may not be receiving any other investigational agents within the past 28 days; NOTE: if agent’s half-life x 5 is < 28 days, patient may have taken it within the last 28 days, provided at least 5 half-lives have passed since having last taken it
• Patients who have had prior therapy with chemokine receptor type 4 (CXCR4) inhibitors
• Patients with one prior relapse on a bevacizumab or an anti-VEGF(R) (i.e., VEGF-trap, vandetanib, cediranib, sunitinib, sorafenib, XL184, etc.) containing regimen are allowed to participate
• Prior therapy with thalidomide and lenalidomide is allowed
• Patients who have received prior treatment with implanted radiotherapy or chemotherapy sources such as wafers of polifeprosan 20 with carmustine
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to plerixafor or bevacizumab
• Anti-coagulation at baseline: * For the first 20 patients to register to trial, no anti-coagulation is allowed; patients requiring therapeutic anticoagulation with warfarin or therapeutic or prophylactic therapy with a low-molecular weight heparin at baseline are excluded * For all subsequent patients screened, patients requiring therapeutic anticoagulation with warfarin at baseline are excluded; however, therapeutic or prophylactic therapy with a low-molecular weight heparin at baseline is acceptable
• Patients must not have a known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhages in the past
• Patients whose MRI scan demonstrates intratumoral hemorrhage or peritumoral hemorrhage are not eligible for treatment if deemed significant by the treating physician
• Patients with gastrointestinal bleeding or any other hemorrhage/bleeding event Common Terminology Criteria for Adverse Events (CTCAE) grade >= 3 within 30 days prior to study entry
• Uncontrolled intercurrent illness including, but not limited to: * Uncontrolled hypertension (for the purpose of this trial, well-controlled hypertension is defined as systolic blood pressure of < 140 mm Hg and diastolic pressure < 90 mm Hg) ** NOTE: the use of anti-hypertensive medication to control hypertension is permitted, provided it is not noted as a prohibited med elsewhere in protocol * Ongoing or active infection * Symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or * Psychiatric illness/social situations that would limit compliance with study requirements
• Patients with greater than 1+ proteinuria on a urine dipstick or equivalent routine laboratory analysis will require further testing with a urine protein to creatinine ratio (UPCR); UPCR must be calculated as follows: UPCR = protein concentration (mg/dL)/creatinine (mg/dL); if the UPCR >= 1 then the patient will not be eligible for study entry; however, if urinalysis or equivalent routine laboratory analysis shows no protein, then UPC testing is not required
• Patients with a history of myocardial infarction, unstable angina, stroke, or transient ischemic attack (TIA) within 6 months prior to planned day 1 of dosing are ineligible
• Patients with a history of non-healing wounds or ulcers, or bone refractures within 3 months of fracture
• Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to planned day 1 of dosing are ineligible
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
• Patients with a history of a different malignancy are ineligible except for the following circumstances: * Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy * Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: ** Cervical cancer in situ ** Basal cell or squamous cell carcinoma of the skin
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with bevacizumab
• Female subjects of child-bearing potential and male subjects with partners of child-bearing potential must agree to use an effective means of birth control while on study therapy and for a minimum of 4 months following last plerixafor dose and 6 months following last bevacizumab dose * Effective birth control includes: ** Birth control pills, depot progesterone, or an intrauterine device plus one barrier method ** or 2 barrier methods * Effective barrier methods are male and female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm) * Hormonal contraceptive methods are not sufficient, as information about any interaction of plerixafor with hormonal contraceptives is not known * Men or women of child-bearing potential (WOCP) who are unwilling or unable to use an acceptable method to avoid pregnancy (noted above) for the entire study period and for up to 2 weeks after the last dose of study drug are excluded from this study