Bavituximab With Radiation and Temozolomide for Patients With Newly Diagnosed Glioblastoma

Phase 2

Completed

• Conditions: Glioblastoma
• Interventions: Drug: Temozolomide; Drug: Bavituximab; Radiation: Radiation

• Registration Number: NCT03139916
• Lead Sponsor: Massachusetts General Hospital

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

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved Bavituximab as a treatment for any disease.

The FDA has approved Temozolomide as a treatment option for this disease.

In this research study, the investigators are studying how the combination of Bavituximab, Temozolomide, and radiation affects this cancer. The current standard care of treatment for newly diagnosed glioblastoma is the combination of Temozolomide and radiation. Temozolomide causes cell death and radiation shrinks and kills the cancer cells. Bavituximab may activate (cause) the immune system to attack the cancer cells as well as target tumor cells themselves to kill them.

Study Timeline

• Study First Submitted: 2017-05-02
• Study First Submitted QC: 2017-05-02
• Study First Posted: 2017-05-04
• Study Start: 2017-09-13
• Primary Completion: 2022-08-31
• Study Completion: 2022-08-31
• Results First Submitted: 2024-02-29
• Status Verified: 2024-05
• Results First Submitted QC: 2024-05-08
• Last Update Submitted: 2024-05-08
• Results First Posted: 2024-05-16
• Last Update Posted: 2024-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

• 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
  • INR/PT ≤1.5 x institutional ULN unless subject is receiving anticoagulant therapy as long as PT or INR is within therapeutic range of intended use of anticoagulants
  • aPTT ≤1.5 x institutional ULN unless subject is receiving anticoagulant therapy as long as PTT is within therapeutic range of intended use of anticoagulants

• < 4 mg dexamethasone daily (or equivalent if on another corticosteroid) at time of start of therapy. Patients on a steroid taper post-surgery and are anticipated to be on <4 mg at time of chemoradiation initiation will be eligible to consent but to initiate treatment on trial, the participant must be on <4 mg or equivalent of steroids otherwise participate will be deemed a screen fail and be replaced.

• The effects of bavituximab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of bavituximab administration.

• Able to undergo an MRI scan and receive gadolinium-based contrast.

• 1 cm3 of available tissue.

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bavituximab + Standard of Care Radiation + Temozolomide	Radiation	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.
Bavituximab + Standard of Care Radiation + Temozolomide	Bavituximab	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.
Bavituximab + Standard of Care Radiation + Temozolomide	Temozolomide	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.

Primary Outcome Measures

Name	Time	Method
Overall Survival at 12 Months (OS12)	12 months	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.

Secondary Outcome Measures

Name	Time	Method
Radiographic Response Rate	every 3 months for 5 years	Radiographic response (RR) is defined as a complete response or partial response per RANO (Response assessment in neuro-oncology) criteria with incorporation of iRANO (immunotherapy response assessment for neuro-oncology) criteria. The radiographic response rate is the percentage of subjects who achieved radiographic response as defined above.
Progression Free Survival (PFS)	every 3 months for up to 5 years	Progression free survival is defined as the time of study entry to time of disease progression, or death due to any cause. Data for subjects who are lost to follow up will be censored at the date when the subject is last known to be alive. PFS results below are reported up to the data cutoff in May 2021.
Overall Survival (OS)	Up to 5 years	Overall survival is defined as the time of study entry to death from any cause. Data for subjects who are lost to follow up will be censored at the date when the subject is last known to be alive. OS results below are reported up to the data cutoff in May 2021.

Trial Locations

Locations (2)

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Massachusetts general Hospital; 🇺🇸 Boston, Massachusetts, United States