A Randomized, Double-blinded, Placebo-controlled Phase 2, Study of (ERC1671/GM CSF/Cyclophosphamide)+Bevacizumab vs. (Placebo Injection/Placebo Pill) +Bevacizumab in the Treatment of Recurrent/Progressive, Bevacizumab naïve Glioblastoma and Glioasarcoma Patients (WHO grade IV malignant gliomas, GBM)

Protocol # :
Disease Sites
Brain and Nervous System
Principal Investigator
Reardon, David, A.
Site Investigator
Jordan, Justin
Site Research Nurses
Chau, Johny, E.
Hibyan, Lauren, M.
Markt, Denise, A.

Trial Description

This phase II clinical trial studies how well ERC1671 plus Granulocyte-macrophage
colony-stimulating factor (GM-CSF) plus Cyclophosphamide with Bevacizumab works compared to
Placebo Injection plus Placebo Pill with Bevacizumab in treating patients with
recurrent/progressive, bevacizumab naïve glioblastoma multiforme and gliosarcoma (World
Health Organization (WHO) grade IV malignant gliomas, GBM).

Eligibility Requirements

Inclusion Criteria:

-Patients must have histologically confirmed diagnosis of a recurrent/progressive WHO grade
IV malignant gliomas (glioblastoma multiforme and gliosarcoma) and meet the following
inclusion criteria:

1. Age ≥18 years of age.

2. Histologic diagnosis of glioblastoma or gliosarcoma (WHO Grade IV).

3. KPS of ≥ 70%.

4. Life expectancy > 12 weeks.

5. First or second relapse of glioblastoma.

6. Previous treatment for glioblastoma must include surgery (biopsy, partial resection,
or full surgical resection), conventional radiation therapy and temozolomide (TMZ).

7. MRI record must be obtained showing the MRI was conducted at least 4 weeks after any
salvage surgery, and at least 12 weeks after radiation therapy, or at least 4 weeks
after radiation for a new lesion outside the prior primary radiation field unless
relapse is confirmed by tumor biopsy or new lesion outside of radiation field, or if
there are two MRIs confirming progressive disease per iRANO that are 8 weeks apart

8. If prior therapy with gamma knife or other focal high-dose radiation, must have
subsequent histologic documentation of local relapse, or relapse with new lesion
outside the irradiated field.

9. Resolution of all chemotherapy or radiation-related toxicities ≤ CTCAE Grade 1
severity, except for alopecia and hematologic toxicity. Patients taking temozolomide
can start study treatment 23 days from the last temozolamide dose.For all other
chemotherapy drugs, study treatment can start as long as all adverse events related to
their prior treatment are no higher than Grade 1.

10. Systemic corticosteroid therapy must be at a dose of ≤ 4 mg of dexamethasone or
equivalent per day during the week prior to Day 1.

11. Pre-surgical Bi-dimensionally measurable disease (as per iRANO criteria)

12. Patients must have normal organ and marrow function as defined below:

- hemoglobin (Hbg) > 9g/dL,

- leukocytes >1,500/mcL

- absolute neutrophil count>1,000/mcL

- CD4 count > 450/mcL

- platelets>125,000/mcL

- Serum bilirubin = 1.5 × upper limit of normal (ULN) or = 3 x ULN if Gilbert's
disease is documented AST(SGOT) and ALT(SGPT)<2.5 X institutional upper limit of

- serum creatinine < 1.5 mg/dl

13. Signed informed consent approved by the Institutional Review Board;

14. If sexually active, patients must agree to take contraceptive measures for the
duration of the treatments.

Exclusion Criteria:

1. Subjects unable to undergo an MRI with contrast.

2. Presence of diffuse leptomeningeal disease

3. History, presence, or suspicion of metastatic disease

4. Administration of immunosuppressive drugs less than 2 weeks prior to first dose of
ERC1671, except dexamethasone for cerebral edema as detailed above;

5. Prior receipt of bevacizumab, or bevacizumab biosimilars or other VEGF- or VEGF
receptor-targeted agents

6. Known contraindication or hypersensitivity to any component of bevacizumab.

7. Evidence of recent hemorrhage on screening MRI of the brain with the following
exceptions: presence of hemosiderin; resolving hemorrhagic changes related to surgery;
presence of punctate hemorrhage in the tumor.

8. Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent
peripheral arterial thrombosis within 6 months prior to Day 1.

9. Evidence of bleeding diathesis or coagulopathy as documented by an elevated PT, PTT or
bleeding time and clinically significant;

10. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
within 6 months prior to Day 1.

11. Urine protein: creatinine ratio ≥ 1.0 at screening;

12. Anticipation of need for major surgical procedure during the course of the study.

13. Serious non-healing wound, ulcer, or bone fracture.

14. Active infection requiring treatment, known immunosuppressive disease, active systemic
autoimmune diseases such as lupus, receipt of systemic immunosuppressive therapy,
human immunodeficiency virus (HIV) infection, Hepatitis B or Hepatitis C

15. Uncontrolled hypertension, blood pressure of > 150 mmHg systolic and > 100 mmHg
diastolic, or history of hypertensive encephalopathy. Subjects with any known
uncontrolled inter-current illness including ongoing or active infection, symptomatic
congestive heart failure (NYHA Gr.2 or >), myocardial infarction, unstable angina
pectoris , within the past 12 months

16. Stroke, transient ischemic attack, unstable angina, myocardial infarction or
congestive heart failure (New York Heart Association Grade II or greater) within the
past 6 months.Unstable or severe intercurrent medical conditions chronic renal
disease, or uncontrolled diabetes mellitus.

17. Women who are pregnant or lactating. All female patients with reproductive potential
must have a negative pregnancy test prior to Day 1 and must use a reliable form of
contraception during study participation.

18. Men refusing to exercise a reliable form of contraception.

19. History of any malignancy (other than glioblastoma) during the last three years except
non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer
or cured, early-stage prostate cancer in a patient with Prostate Surface Antigen (PSA)