ERC1671/GM-CSF/Cyclophosphamide for the Treatment of Glioblastoma Multiforme

  • STATUS
    Recruiting
  • End date
    Mar 3, 2023
  • participants needed
    84
  • sponsor
    University of California, Irvine
Updated on 3 March 2021
corticosteroids
measurable disease
sargramostim
steroid therapy
MRI
dexamethasone
progressive disease
neutrophil count
bevacizumab
glioblastoma multiforme
temozolomide
gliosarcoma
malignant glioma
placebo pill

Summary

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 nave glioblastoma multiforme and gliosarcoma (World Health Organization (WHO) grade IV malignant gliomas, GBM).

Description

This is a blinded Phase II study of ERC1671 in combination with bevacizumab in patients with relapsed, bevacizumab naive glioblastoma. The patients who will be randomized (in a 1:1 ratio) to receive either ERC 1671 in combination with GM-CSF and cyclophosphamide or a placebo control, in combination with bevacizumab. The study will be double blinded.

ERC1671/GM-CSF will be intradermally administered, while cyclophosphamide is orally administered. GM-CSF dose is 500mcg fixed dose and cyclophosphamide dose is 50 mg/day. Bevacizumab or approved bevacizumab biosimilars are administered as standard of care at 10 mg/kg every 2 weeks.

The treatment cycles will be 28 days long.

Details
Condition Glioma, gliosarcoma, Glioblastoma Multiforme, Gliomas, glioblastoma
Treatment cyclophosphamide, bevacizumab, GM-CSF, ERC1671, Oral Control (Sucrose pill), Injectable control (Sodium Chloride Injection United States Pharmacopeia (USP) (0.9%)), Bevacizumab/Bevacizumab Biosimilar
Clinical Study IdentifierNCT01903330
SponsorUniversity of California, Irvine
Last Modified on3 March 2021

Eligibility

Yes No Not Sure

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
Age 18 years of age
Histologic diagnosis of glioblastoma or gliosarcoma (WHO Grade IV)
KPS of 70%
Life expectancy > 12 weeks
First or second relapse of glioblastoma
Previous treatment for glioblastoma must include surgery (biopsy, partial resection, or full surgical resection), conventional radiation therapy and temozolomide (TMZ)
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
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
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
Systemic corticosteroid therapy must be at a dose of 4 mg of dexamethasone or equivalent per day during the week prior to Day 1
Pre-surgical Bi-dimensionally measurable disease (as per iRANO criteria)
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 normal
serum creatinine < 1.5 mg/dl
Signed informed consent approved by the Institutional Review Board
If sexually active, patients must agree to take contraceptive measures for the duration of the treatments

Exclusion Criteria

Subjects unable to undergo an MRI with contrast
Presence of diffuse leptomeningeal disease
History, presence, or suspicion of metastatic disease
Administration of immunosuppressive drugs less than 2 weeks prior to first dose of ERC1671, except dexamethasone for cerebral edema as detailed above
Prior receipt of bevacizumab, or bevacizumab biosimilars or other VEGF- or VEGF receptor-targeted agents
Known contraindication or hypersensitivity to any component of bevacizumab
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
Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 1
Evidence of bleeding diathesis or coagulopathy as documented by an elevated PT, PTT or bleeding time and clinically significant
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
Urine protein: creatinine ratio 1.0 at screening
Anticipation of need for major surgical procedure during the course of the study
Serious non-healing wound, ulcer, or bone fracture
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
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
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
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
Men refusing to exercise a reliable form of contraception
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) level <ULN
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