A Study of Subcutaneous Bevacizumab in Relapsed / Progressive Glioblastoma

NCT02157103 | Completed Phase 2 Results DMC

• 2 other identifiers: IRB00062998Winship2299-12
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

STUDY BACKGROUND: This research will involve patients with glioblastoma. The drug bevacizumab (Avastin) is FDA approved for the treatment of glioblastoma that gets worse after standard therapy. For glioblastoma, bevacizumab is given by vein every 14 days. The purpose of this study is to see if bevacizumab works as well when it is given as a daily subcutaneous shot as it does when given intravenously. A subcutaneous shot is like an insulin shot or a heparin shot. The dose of bevacizumab given on this study is in total slightly lower than the FDA approved dose for glioblastoma. STUDY DESCRIPTION: About 10 people will take part in the study. Participants or caregivers will be educated on injection and given prefilled syringes to take home. Participants or caregivers will administer bevacizumab subcutaneously each day. The bevacizumab will be stored in the refrigerator. Follow up visits will be weekly for the first 3 weeks, then every 3 weeks. After 18 weeks, the follow up interval can be increased to every 6 weeks at the treating physician's discretion. Participants can keep taking the bevacizumab until:

• Tests show that they are not benefiting from it,
• The participant has a bad side effect related to study treatment,
• The participant can no longer comply with study requirements, or
• The participant or doctor feels it is no longer in the participant's best interest.

Conditions

Glioblastoma

Keywords

GBM; Glioblastoma; Bevacizumab; Avastin; Subcutaneous

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Change in Peritumoral Enhancement/Edema

  To describe MRI response regarding edema and enhancement of glioblastoma and radiation-related brain enhancement when treated with subcutaneous bevacizumab daily. The therapeutic benefit of bevacizumab as regards glioblastoma multiforme (GBM) is largely due to the normalization of brain vasculature. This normalization appears on contrast-enhanced MRI as a reduction in enhancement and reduction in edema. For purposes of this study, any reduction in enhancement/edema by 25% or more will be considered a response.

  1 cycle (3 weeks)

Secondary Outcomes (2)

• Number of Toxicities Reported in Study Participants

  During first 3 weeks of study

• Number of Participants With Change in Edema After Conversion From Study Treatment to Intravenous Bevacizumab

  Within 2 months of starting intravenous bevacizumab

Study Arms (1)

Bevacizumab

EXPERIMENTAL

Cycle 1 (each cycle is 3 weeks): Bevacizumab 25 mg in 1 ml subcutaneously daily.

Drug: Bevacizumab 25 mg in 1 ml subcutaneously daily

Interventions

Bevacizumab 25 mg in 1 ml subcutaneously daily DRUG

Bevacizumab delivered by subcutaneous injection instead of intravenous infusion.

Also known as: Avastin

Bevacizumab

Eligibility Criteria

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

You may qualify if:

• Diagnosis: Participants with glioblastoma are eligible for this study. These will include
• Those with a histologically proven diagnosis of glioblastoma who have developed new changes on MRI following primary treatment.
• Those who received primary treatment for a histologically proven lower grade (2 or 3) glioma and who now progress with radiographic characteristics of transformed glioma.
• Disease status: Patients must have abnormal enhancement on contrast enhanced MRI of the brain. They must be patients for whom bevacizumab is indicated and appropriate, as drug will be charged to insurance.
• Participants with newly detected enhancement are eligible, with bevacizumab treatment hoped to prevent symptoms.
• Participants with stable enhancement / edema are eligible if they require corticosteroids to control symptoms, and it is thought bevacizumab treatment might allow lowering of the corticosteroid dose or improvement of symptoms.
• Performance status: Eastern Cooperative Oncology Group (ECOG) 0-3.
• Age: Greater than 18 years.
• Life expectancy: \> 3 months.
• Prior therapy:
• Anti-VEGF treatments: 3 months must have elapsed between any prior anti-VEGF treatment (for example, given as a component of primary treatment) and study participation. These therapies include bevacizumab, cediranib, axitinib, sunitinib as well as other therapeutics targeting VEGF.
• Other anti-cancer treatments: Treatments in this category include chemotherapy and targeted therapies not targeting VEGF. 14 days must have elapsed since discontinuation of prior chemotherapeutic treatments for glioma and study treatment.
• Radiation: Radiation is integral to the primary treatment of glioma. All participants on this study must have had prior radiation to the brain. Radiation must have been completed 14 days prior to first study treatment.
• Surgery: 14 days must have elapsed since prior major surgery.
• Organ function requirements:

You may not qualify if:

• People who progress with only nonenhancing tumor on MRI are ineligible. Patients must have some component of abnormal enhancement on contrast enhanced MRI of the brain. Combinations of nonenhancing and enhancing tumor are eligible.
• Pregnancy or breast-feeding: Pregnant or breast-feeding women will not be entered on this study.
• Renal insufficiency: Patients with a creatinine clearance of less than 50 are ineligible.
• Proteinuria: Patients with 2+ proteinuria/Moderate or more at baseline are ineligible.
• Comorbidities: Patients may not have any baseline comorbidities or laboratory abnormalities which would be of grade 3 or worse if graded as toxicities by CTCAE (excepting alopecia). An exception is also made for neurologic comorbidities (eg ataxia, aphasia) arising as a consequence of the brain tumor; symptoms severe enough to warrant medical treatment as is offered on this study are by definition grade 3.
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.
• Illness or any other circumstances (as defined by the investigator), which would preclude safe performance of study procedures or compromise the ability of the patient to consent to study.

Sponsors & Collaborators

• Emory University: lead

Study Sites (2)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Winship Cancer Institutute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: William L. Read, MD, Principal Investigator
• Organization: Emory University

william.l.read@emory.edu

404-778-1900

Study Officials

• William L. Read, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 14, 2014
• First Posted: June 5, 2014
• Study Start: January 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: January 1, 2018
• Last Updated: May 17, 2018
• Results First Posted: April 13, 2018

Record last verified: 2018-04

Locations

US (2)