Bavituximab With Radiation and Temozolomide for Patients With Newly Diagnosed Glioblastoma

NCT03139916 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-037
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying a combination of drugs with radiation as a possible treatment for Glioblastoma. The drugs involved in this study are:

• Bavituximab
• Temozolomide

Conditions

Glioblastoma

Keywords

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival at 12 Months (OS12)

  Overall survival is defined as the time from study entry to death from any cause. OS12 is the percentage of subjects who are alive 12 months after study entry. Data for subjects who are lost to follow up prior to documented death will be counted as deaths at the last assessment date when the subject is known to be alive.

  12 months

Secondary Outcomes (3)

• Radiographic Response Rate

  every 3 months for 5 years

• Progression Free Survival (PFS)

  every 3 months for up to 5 years

• Overall Survival (OS)

  Up to 5 years

Study Arms (1)

Bavituximab + Standard of Care Radiation + Temozolomide

EXPERIMENTAL

Cycle 1 consists of 6 weeks (42 days) of chemoradiation. Radiation therapy is administered per standard of care. Bavituxumab 3 mg/kg IV administration starts during the 1st week of chemoradiation and continues weekly. Temozolomide 75/m2 is administered orally once daily. Cycle 2 is 4 weeks (28 days) long and Bavituxumab 3 mg/kg IV administration occurs weekly. Cycle 3 and beyond are each 4 weeks (28 days) long. Bavituxumab 3 mg/kg IV administration occurs weekly for a cumulative total of 18 weeks; treatment may continue beyond 18 weeks at the discretion of the treating physician if the participant is deriving clinical benefit. Temozolomide 150-200 mg/m2 is administered orally once daily on days 1-5 in cycles 3 and 4.

Drug: Temozolomide; Drug: Bavituximab; Radiation: Radiation

Interventions

Temozolomide DRUG

Temozolomide causes cell death and shrinks and kills the cancer cells

Also known as: Temodar

Bavituximab + Standard of Care Radiation + Temozolomide

Bavituximab DRUG

Bavituximab may activate (cause) the immune system to attack the cancer cells

Bavituximab + Standard of Care Radiation + Temozolomide

Radiation RADIATION

Radiation causes cell death and shrinks and kills the cancer cells.

Bavituximab + Standard of Care Radiation + Temozolomide

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed newly diagnosed glioblastoma or glioblastoma variant (ex. gliosarcoma), including documentation of unmutated isocitrate dehydrogenase (IDH) by immunohistochemistry (sequencing not required).
• Participants must have 1-4 cm2 measurable disease (4 cm2 is the maximal size). See Section 11 for the evaluation of measurable disease. Disseminated GBM is not allowed.
• No prior immunotherapy allowed or prior alkylating agents or prior radiation to the brain.
• Age \>17 years since adult GBM is biologically different from pediatric GBM and there is no data for bavituximab in pediatric populations.
• Karnofsky ≥60%, see Appendix A
• Life expectancy of greater than 6 months.
• Participants must have normal organ and marrow function as defined below:
• leukocytes ≥3,000/mcL
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• total bilirubin within normal institutional limits (unless patient has Gilbert's syndrome in which total bilirubin should be ≤ 2xULN)
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
• creatinine within normal institutional limits OR
• creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal(using Cockcroft Gault Formula)
• negative serum pregnancy test in WOCBP

You may not qualify if:

• Participants who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to bavituximab.
• Participants receiving any medications or substances that are moderate and/or potent enzyme inducers or inhibitors which may have an effect on the metabolism of bavituximab. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product (Appendix C for partial list).
• 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.
• Pregnant women are excluded from this study because bavituximab is an immunotherapy agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with bavituximab breastfeeding should be discontinued if the mother is treated with bavituximab. These potential risks may also apply to other agents used in this study.
• HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with bavituximab. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
• Participants with other active malignancy in the past 3 years excluding in situ tumors.
• Participants must meet the following windows from procedures (there is no window required for port placement since there is no anticipated impact on wound healing with bavituximab):
• Major surgery (ex. craniotomy) within 3 weeks of initiation of treatment.
• Brain biopsy within 2 weeks
• Participants with history of bleeding disorder/coagulopathy.
• Participants with history of chronic or acute hepatitis C or B infection

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Peregrine Pharmaceuticals: collaborator
• National Comprehensive Cancer Network: collaborator

Study Sites (2)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts general Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Ly KI, Richardson LG, Liu M, Muzikansky A, Cardona J, Lou K, Beers AL, Chang K, Brown JM, Ma X, Reardon DA, Arrillaga-Romany IC, Forst DA, Jordan JT, Lee EQ, Dietrich J, Nayak L, Wen PY, Chukwueke U, Giobbie-Hurder A, Choi BD, Batchelor TT, Kalpathy-Cramer J, Curry WT, Gerstner ER. Bavituximab Decreases Immunosuppressive Myeloid-Derived Suppressor Cells in Newly Diagnosed Glioblastoma Patients. Clin Cancer Res. 2023 Aug 15;29(16):3017-3025. doi: 10.1158/1078-0432.CCR-23-0203.

  PMID: 37327319 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide; bavituximab; Radiation

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)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Physical Phenomena

Results Point of Contact

• Title: Elizabeth R. Gerstner, MD
• Organization: Massachusetts General Hospital

egerstner@mgh.harvard.edu

617-724-8770

Study Officials

• Elizabeth R Gerstner, MD

  Massachusetts General Hospital

  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: Principle Investigator

Study Record Dates

• First Submitted: May 2, 2017
• First Posted: May 4, 2017
• Study Start: September 13, 2017
• Primary Completion: August 31, 2022
• Study Completion: August 31, 2022
• Last Updated: May 16, 2024
• Results First Posted: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)