Plerixafor (AMD3100) and Bevacizumab for Recurrent High-Grade Glioma
Phase: Phase 1
Diagnosis: Brain/Neuro Cancer: Recurrent Glioblastoma
NCT ID: NCT01339039
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 10-329
Plerixafor in combination with bevacizumab is a drug combination that may stop cancer cells from growing abnormally. Bevacizumab, also known as Avastin, is FDA approved for use in patients with recurrent glioblastoma and has been studied extensively in other types of solid tumors. Plerixafor, also known as Mozobil, is FDA approved for use in patients with non-Hodgkin's lymphoma and multiple myeloma and has been used in treatment for other cancers. Information from experiments in laboratories suggests that the combination of plerixafor and bevacizumab may help prevent the growth of gliomas. Part 1: The investigators are looking for the highest dose of plerixafor that can be given safely with bevacizumab (with a 21 days on/7 days off regimen of plerixafor). The investigators will also do blood tests to find out how the body uses and breaks down the drug combination. Part 2: The investigators are looking to see if plerixafor can get past the blood-brain barrier and into brain tumors. The investigators will also do blood tests to find out how the body uses and breaks down the drug combination. Part 3: The investigators are looking for for more information re: safety and tolerability of plerixafor in combination with bevacizumab (with a 28 days on/0 days off regimen of plerixafor). The investigators will also do blood tests to find out how the body uses and breaks down the drug combination.
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital
Patrick Wen, MD,
Dana-Farber Cancer Institute
Elizabeth Gerstner, MD,
Massachusetts General Hospital
Dana-Farber Cancer Institute:
Massachusetts General Hospital:
Cancer Trials Call Center, 877-789-6100
- 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 supratentorial disease without infratentorial involvement.
- Unequivocal progression by MRI or CT
- 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). Relapse is defined as progression following initial
- 18 years of age or older
- Life expectancy of greater than 8 weeks
- Karnofsky performance status of 60 or greater
- Normal organ and marrow function as outlined in the protocol
- Protocol treatment must begin within 5 consecutive days after registration
- Patients enrolled in Part 2 must be willing to undergo surgical resection and have
pre-treatment archival tumor tissue available for molecular analysis
- Women of child-bearing potential must have a negative serum or urine pregnancy test
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 the duration of the study participation.
- Ability to understand and the willingness to sign a written informed consent
- Patients who have had prior chemotherapy within the past 4 weeks (6 weeks for
nitrosoureas or mitomycin C) or those who have not recovered from adverse events due
to agents administered more than 4 weeks earlier. Patients who received
non-cytotoxic drug therapy must be off treatment for at least 2 weeks.
- Patients who have received any form of cranial radiation within 3 months of study
- 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
- Patients who have had prior therapy with CXCR4 inhibitors or anti-VEGF targeted
agents. 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.
- 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
- Patients with gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE
Grade > 3 within 30 days prior to study entry.
- Uncontrolled intercurrent illness including but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
- 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
- History of non-healing wounds or ulcers, or bone refractures within 3 months of
- HIV-positive patients on combination antiretroviral therapy
- Participants 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, and basal cell or squamous cell carcinoma of the skin.
- Pregnant women
- Men or women of childbearing potential who are unwilling or unable to use an
acceptable method to avoid pregnancy for the entire study period and for up to 2
weeks after the last dose of study drug.