This phase 0/I trial studies how well continuous low-dose capecitabine given alone and with bevacizumab works in targeting myeloid derived suppressor cells (MDSCs) in patients with glioblastoma that has either returned after being treated by a previous therapy or has continued to progress despite being treated. MDSCs are a group of immune cells found in the tissue and blood that may reduce the ability of the immune system to fight tumors. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumors cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Giving a continuous low dose of capecitabine, with and without bevacizumab, may help reduce the number of MDSCs found in the tumor and be a better treatment for patients with glioblastoma.
Additional locations may be listed on ClinicalTrials.gov for NCT02669173.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To achieve a 20-fold MDSC reduction in the concentration of circulating MDSCs after treatment with low dose capecitabine.
SECONDARY OBJECTIVES:
I. To determine the concentration of circulating MDSCs in patients with recurrent glioblastoma after treatment with low dose capecitabine.
II. To determine the concentration of tissue MDSCs and T-regulatory cells in resected glioblastoma after treatment with low dose capecitabine.
III. To determine the safety and toxicity of continuous low dose capecitabine alone and with standard dose bevacizumab.
IV. To obtain a signal for efficacy as measured by progression-free survival rate at 6 months.
OUTLINE: This is a dose-escalation study of capecitabine.
Patients receive low-dose capecitabine orally (PO) once daily (QD) beginning 5-7 days before surgery with the final dose given the morning of surgery and then again beginning no sooner than 10 days post-operation and no later than 28 days post-operation. Patients also receive bevacizumab intravenously (IV) over on days 1 and 15 beginning in cycle 2. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Lead OrganizationCase Comprehensive Cancer Center
Principal InvestigatorDavid Marc Peereboom
