Bavituximab With Radiation and Temozolomide for Patients With Newly Diagnosed Glioblastoma

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.

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