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

NCT01903330 | Active Not Recruiting Phase 2 DMC

• 3 other identifiers: UCI13-14 ERC1671-H02 2013-9863UCI 13-142013-9863
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 3

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

Conditions

Glioblastoma; Gliosarcoma

Keywords

ERC1671; GM-CSF; Cyclophosphamide; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• Overall Survival at 12 months of patients with recurrent, bevacizumab naïve glioblastoma treated with ERC1671 in combination with GM-CSF and cyclophosphamide plus bevacizumab as compared with patients receiving bevacizumab plus placebo controls.

  To evaluate overall survival in patients with with recurrent, bevacizumab naïve glioblastoma treated with ERC1671 in combination with GM-CSF and cyclophosphamide plus bevacizumab as compared with patients receiving bevacizumab plus placebo controls.

  12 months

Secondary Outcomes (4)

• Rate of Progression-Free Survival

  12 months

• Immune Response

  12 months

• Percentage of Grade 3-5 Adverse Events

  12 months

• Rate of Radiographic Response as assessed using MacDonald Criteria or IRANO

  12 month

Study Arms (2)

(ERC1671/GM-CSF/Cyclophosphamide)+bevacizumab/bevacizumab biosimilar

EXPERIMENTAL

ERC1671 and 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 will be repeated every 28 days until progression of disease or intolerance.

Drug: ERC1671; Drug: GM-CSF; Drug: Cyclophosphamide; Drug: Bevacizumab/Bevacizumab Biosimilar

(Placebo Injection/Placebo Pill) +Bevacizumab/bevacizumab biosimilar

PLACEBO COMPARATOR

The control group will have the same study schedule except that the patients will be receiving the Oral Control on the Cyclophosphamide treatment days and the Injectable control on the GM-CSF + ERC1671 treatment days. The control group will receive bevacizumab or approved bevacizumab biosimilar just as the active treatment group above. The treatment will be repeated every 28 days until progression of disease or intolerance.

Drug: Oral Control (Sucrose pill); Drug: Injectable control (Sodium Chloride Injection United States Pharmacopeia (USP) (0.9%)); Drug: Bevacizumab/Bevacizumab Biosimilar

Interventions

ERC1671 DRUG

Given intradermally

Also known as: Gliovac

(ERC1671/GM-CSF/Cyclophosphamide)+bevacizumab/bevacizumab biosimilar

GM-CSF DRUG

Given intradermally

Also known as: Leukine®, sargramostim

(ERC1671/GM-CSF/Cyclophosphamide)+bevacizumab/bevacizumab biosimilar

Cyclophosphamide DRUG

Given PO. Drug class: Alkylating Agent; Antineoplastic Agent; Nitrogen Mustard.

Also known as: 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate

(ERC1671/GM-CSF/Cyclophosphamide)+bevacizumab/bevacizumab biosimilar

Oral Control (Sucrose pill) DRUG

Given PO

(Placebo Injection/Placebo Pill) +Bevacizumab/bevacizumab biosimilar

Injectable control (Sodium Chloride Injection United States Pharmacopeia (USP) (0.9%)) DRUG

Given IV

(Placebo Injection/Placebo Pill) +Bevacizumab/bevacizumab biosimilar

Bevacizumab/Bevacizumab Biosimilar DRUG

Given IV. Drug class: Immunological Agent; Monoclonal Antibody.

Also known as: Avastin, MVASI, bevacizumab-awwb, bevacizumab-bvzr, ZIRABEV

(ERC1671/GM-CSF/Cyclophosphamide)+bevacizumab/bevacizumab biosimilar; (Placebo Injection/Placebo Pill) +Bevacizumab/bevacizumab biosimilar

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Epitopoietic Research Corporation: lead
• University of California, Irvine: collaborator

Study Sites (3)

University of California, Irvine

Orange, California, 92868, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Schijns VE, Pretto C, Devillers L, Pierre D, Hofman FM, Chen TC, Mespouille P, Hantos P, Glorieux P, Bota DA, Stathopoulos A. First clinical results of a personalized immunotherapeutic vaccine against recurrent, incompletely resected, treatment-resistant glioblastoma multiforme (GBM) tumors, based on combined allo- and auto-immune tumor reactivity. Vaccine. 2015 May 28;33(23):2690-6. doi: 10.1016/j.vaccine.2015.03.095. Epub 2015 Apr 10.

  PMID: 25865468 DERIVED

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim; Cyclophosphamide; Sucrose; Bevacizumab

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)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Disaccharides; Oligosaccharides; Polysaccharides; Sugars; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Study Officials

• Daniela A. Bota, MD, PhD

  University of California, Irvine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2013
• First Posted: July 19, 2013
• Study Start: March 1, 2014
• Primary Completion: March 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: March 5, 2025

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)