A Study of Subcutaneous Bevacizumab in Relapsed / Progressive Glioblastoma

• ClinicalTrials.gov Identifier: NCT02157103
• Recruitment Status: Completed
• First Posted: June 5, 2014
• Results First Posted: April 13, 2018
• Last Update Posted: May 17, 2018
• Sponsor: Emory University
• Information provided by (Responsible Party): William Read, Emory University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Glioblastoma	Drug: Bevacizumab 25 mg in 1 ml subcutaneously daily	Phase 2

  Show Detailed Description

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Subcutaneous Bevacizumab in Relapsed / Progressive Glioblastoma
• Actual Study Start Date: January 2014
• Actual Primary Completion Date: November 2016
• Actual Study Completion Date: January 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Bevacizumab; Cycle 1 (each cycle is 3 weeks): Bevacizumab 25 mg in 1 ml subcutaneously daily.	Drug: Bevacizumab 25 mg in 1 ml subcutaneously daily; Bevacizumab delivered by subcutaneous injection instead of intravenous infusion.; Other Name: Avastin

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Change in Peritumoral Enhancement/Edema [ Time Frame: 1 cycle (3 weeks) ]
   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.

Secondary Outcome Measures :

1. Number of Toxicities Reported in Study Participants [ Time Frame: During first 3 weeks of study ]
   Subcutaneous bevacizumab may have toxicities unique to the subcutaneous administration and not seen with intravenous bevacizumab. During the first 3 weeks we will watch for such toxicities. Toxicities will be described and graded using the Common Toxicity Criteria for Adverse Effects (CTCAE) v3.
2. Number of Participants With Change in Edema After Conversion From Study Treatment to Intravenous Bevacizumab [ Time Frame: Within 2 months of starting intravenous bevacizumab ]
   Participants may switch from subcutaneous bevacizumab on study to standard of care intravenous bevacizumab. In these participants, we will measure decrease of edema after this switch. A further decrease in edema after making this switch would suggest intravenous to be superior to subcutaneous as regards decreasing edema. The therapeutic benefit of bevacizumab as regards GBM is largely due to the normalization of brain vasculature. This normalization appears on contrast-enhanced MRI as a reduction in edema. For purposes of this study, any reduction in edema by 25% or more will be considered a response.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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:

  • Creatinine clearance of 50 or greater.
  • Absolute neutrophil count of 1500 or greater.
• Blood pressure requirements: Participants must have a baseline blood pressure of 160/90 or less. Participants requiring medicines to control blood pressure are eligible.
• Informed consent: All patients must sign a written informed consent.
• Urine pregnancy test: Women of childbearing age must have a negative urine pregnancy test.

Exclusion Criteria:

• 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.

Contacts and Locations

Locations

United States, Georgia

Emory University Hospital Midtown

Atlanta, Georgia, United States, 30308

Emory University Winship Cancer Institutute

Atlanta, Georgia, United States, 30322

Sponsors and Collaborators

Emory University

Investigators

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

More Information

• Responsible Party: William Read, Principal Investigator, Emory University
• ClinicalTrials.gov Identifier: NCT02157103 History of Changes
• Other Study ID Numbers: IRB00062998; Winship2299-12 ( Other Identifier: Winship Cancer Institute )
• First Posted: June 5, 2014
• Results First Posted: April 13, 2018
• Last Update Posted: May 17, 2018
• Last Verified: April 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by William Read, Emory University:

GBM; Glioblastoma; Bevacizumab; Avastin; Subcutaneous

Additional relevant MeSH terms:

Glioblastoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Bevacizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors