Capecitabine + Bevacizumab in Patients With Recurrent Glioblastoma

NCT02669173 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CASE7315
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study involves participants with recurrent glioblastoma brain tumors (GBM). This means that a participant's brain tumor has either returned after being treated by a previous therapy, or has continued to progress despite being treated. The purpose of this study is to provide proof of concept that suppression of MDSCs (myeloid-derived suppressor cells) is feasible in patients with GBM. Rather than targeting tumor cells or immune checkpoints, which has been the focus of recent therapeutic efforts, direct targeting of MDSCs with low dose capecitabine has the potential to reverse the immunosuppressed microenvironment of GBM and thereby reduce tumors

Conditions

Glioblastoma

Keywords

Myeloid derived suppressor cells; brain tumor; MDSC; GBM; recurrent

Outcome Measures

Primary Outcomes (1)

• Change of concentration in circulating MDSCs after treatment with low dose capecitabine

  baseline to eight months after

Secondary Outcomes (4)

• Concentration of MDSCs in resected glioblastoma after treatment with low dose capecitabine

  Eight months

• Concentration of T-regulatory cells after treatment with low dose capecitabine

  Eight months

• Number of participants with adverse events relating to treatment with low-dose capecitabine alone as assessed by CTCAE v4.0

  Nine months

• Number of participants with adverse events relating to treatment with low-dose capecitabine combined with bevacizumab as assessed by CTCAE v4.0

  Nine months

Other Outcomes (1)

• To obtain a signal for efficacy as measured by progression-free survival rate at 6 months

  Six months

Study Arms (1)

Treatment: Capecitabine + Bevacizumab

EXPERIMENTAL

Capecitabine, PO dose to be determined by phase 1 dose escalation, cycle length 28 days. Treated with Bevacizumab, IV, 10 mg/kg days 1, 15 every 28 days, until progression.

Drug: Capecitabine; Drug: Bevacizumab

Interventions

Bevacizumab DRUG

Drug given by IV, 10 mg/kg days 1, 15 every 28 days, until progression.

Treatment: Capecitabine + Bevacizumab

Capecitabine DRUG

Drug given orally. Dose to be determined by phase 1 dose escalation, cycle length 28 days. Treatment until progression

Treatment: Capecitabine + Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically or cytologically confirmed WHO grade 4 glioma for which a clinically indicated tumor resection is planned.
• Subjects must not have received capecitabine or bevacizumab for this disease.
• Performance status: Karnofsky Performance status ≥ 60%
• Subjects must have adequate organ function and laboratory parameters within 21 days of study entry as defined below:
• Hemoglobin ≥ 8 g/dl
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Total bilirubin \< 1.5 x institutional upper limit of normal (ULN)
• AST (SGOT) ≤ 3 X institutional ULN
• ALT (SGPT) ≤ 3 X institutional ULN
• Calculated creatinine clearance ≥ 50 mL/min
• Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio. For UPC ratio \> 0.5, 24-hour urine protein must be obtained and must be \< 1000 mg.
• Prothrombin time/international normalized ratio (PT/INR) \< 1.4 for patients not on warfarin
• Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria:
• No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)

You may not qualify if:

• Prior treatment toxicities not resolved to ≤ Grade 1 according to NCI CTCAE Version 4.0 except alopecia and neuropathy.
• Subjects receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to capecitabine or bevacizumab.
• Subjects with 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 study requirements.
• HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with capecitabine and/or bevacizumab. In addition, these subjects are at increased risk of lethal infections when treated with marrow suppressive therapy.
• Other malignancy within the past 2 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or vulva; c) prostate cancer of Gleason Score 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder, or benign tumors of the adrenal or pancreas.
• Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events Version 4.0 \[CTCAE v.4.0\] diarrhea of any etiology at screening).
• Active infection with hepatitis B or hepatitis C virus.
• Pregnant or breastfeeding.
• Known dihydropyrimidine dehydrogenase deficiency.
• Known hypersensitivity to 5-fluorouracil, capecitabine, bevacizumab or to any component of the investigational products or compounds of similar chemical composition.
• Unable or unwilling to swallow tablets.
• Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that would, in the Investigator's judgment, make the patient inappropriate for this study.
• Arterial ischemic event (e.g., unstable angina, myocardial infarction, stroke) within 6 months of study entry

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

Related Publications (1)

• Peereboom DM, Alban TJ, Grabowski MM, Alvarado AG, Otvos B, Bayik D, Roversi G, McGraw M, Huang P, Mohammadi AM, Kornblum HI, Radivoyevitch T, Ahluwalia MS, Vogelbaum MA, Lathia JD. Metronomic capecitabine as an immune modulator in glioblastoma patients reduces myeloid-derived suppressor cells. JCI Insight. 2019 Nov 14;4(22):e130748. doi: 10.1172/jci.insight.130748.

  PMID: 31600167 DERIVED

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms; Recurrence

Interventions

Capecitabine; Bevacizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David Peereboom, MD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2016
• First Posted: February 1, 2016
• Study Start: October 11, 2016
• Primary Completion: January 7, 2025
• Study Completion: January 7, 2025
• Last Updated: February 23, 2026

Record last verified: 2026-02

Locations

US (1)