Optune(NOVOTTF-100A)+ Bevacizumab+ Hypofractionated Stereotactic Irradiation Bevacizumab-Naive Recurrent Glioblastoma (GCC 1344)

NCT01925573 | Terminated Results DMC FDA Device

• 1 other identifier: HP-00056719
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This protocol is designed to generate and provide preliminary data to determine the safety and activity of combination therapy using tumor treating fields (TTFields; Optune(NovoTTF-100A); Novocure, Haifa, Israel), a novel FDA-approved therapy utilizing alternating electric fields to inhibit tumor cell growth, along with bevacizumab (Avastin; Genentech, San Francisco, CA), a humanized monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), and hypofractionated stereotactic radiotherapy, a highly-focal abbreviated course of brain irradiation, in the treatment of patients with bevacizumab-naive recurrent GBM. Each of these individual therapies, and also several combinations in doublets, has already demonstrated safety and efficacy but prospective clinical data for the concurrent combination of all three therapies are lacking.

Conditions

RECURRENT GLIOBLASTOMA; Brain Tumor

Keywords

RECURRENT GLIOBLASTOMA; Brain Tumor

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Grade 3 or High Toxicity/Adverse Event (Primary Measure)

  The ability to complete protocol treatment (i.e. tri-modality treatment) without undue acute toxicity as defined below * : \<40% rate of Grade 3 or higher nonhematologic toxicity. * : \<15% rate of Grade 4 or higher nonhematologic toxicity * : \<5% rate of Grade 4+ scalp dermatitis * : \<50% rate of Grade 2-3 scalp dermatitis Early stopping rules: Two or more Grade 2 or higher symptomatic CNS hemorrhages; Eight treatment-related Grade 3 or higher non hematologic or Grade 4 or higher hematologic toxicities.

  6 months

Study Arms (1)

Optune+RT+Bevacuzimab

OTHER

Part 1: Bevacizumab every 2 weeks plus Optune daily for 4 week cycles. Part 2: RT will begin post 3 round of Bevacizumab (hypofractionated radiotherapy: 30 Gy in 5 fractions or 35 Gy in 10 fractions) per physician choice. Part 3: Adjuvant Bevacizumab and Optune

Device: Optune(NOVOTTF-100A)

Interventions

Optune(NOVOTTF-100A) DEVICE

Optune+RT+Bevacuzimab

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with recurrent or progressive glioblastoma or other grade IV malignant glioma (i.e. glioblastoma, gliosarcoma, giant cell glioblastoma, etc.) who have failed prior radiation but who have not progressed/recurred on bevacizumab. Patients will be eligible if the original histology was lower-grade glioma and subsequent diagnosis of glioblastoma or gliosarcoma is made.
• Patients with any number of recurrences are allowed. 3 Brain MRI demonstrates an enhancing tumor \< 8 cm in largest diameter. 4 Karnofsky performance status ≥ 70%. 5 Age ≥ 22 years old. 6 Patients must have the following laboratory values:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin (Hgb) \> 10 g/dL
• Serum total bilirubin: ≤ 1.5 x ULN
• ALT and AST ≤ 3.0 x ULN
• Adequate Renal Function: BUN and Cr \< 2.0 x ULN
• Blood coagulation parameters: international normalized ratio (INR) ≤ 1.5 for patients not on warfarin 7 Minimum interval since completion of radiation treatment is 12 weeks. 8 History of standard dose CNS radiotherapy: radiation of 60 Gy in 30 fractions or 59.4 Gy in 1.8 Gy fractions, or equivalent or lower doses.
• Minimum interval since last major surgery, open biopsy, or significant traumatic injury is 4 weeks 10 Minimum interval since last drug therapy:
• weeks since last non-cytotoxic therapy
• weeks must have elapsed since the completion of a non-nitrosourea-containing chemotherapy regimen
• weeks since the completion of a nitrosourea-containing chemotherapy regimen. 11 Patients must have signed an approved informed consent and authorization permitting release of personal health information.
• Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Female patients of child-bearing potential must have a negative pregnancy test.
• Patients with history of prior invasive malignancy (except non-melanomatous skin cancer) must have been disease free for a minimum of 1 year.

You may not qualify if:

• Any prior therapy with bevacizumab 2 Any significant hemorrhage defined as \> 1 cm diameter of blood seen on the MRI or CT scan. If \> 1 cm of acute blood is detected, the patient will be ineligible for this trial.
• Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury.
• Patients with impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• History or presence of serious uncontrolled ventricular arrhythmias
• Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE)
• Uncontrolled hypertension (defined by a SBP ≥ 160 mm Hg or DBP ≥ 100 mm Hg while on anti-hypertensive medications) or history of hypertensive crisis or hypertensive encephalopathy, stroke, TIA, symptomatic peripheral vascular disease, or grade 2 CHF 5 Patients with cirrhosis, or active viral or non-viral hepatitis. 6 Patients with peptic ulcer, abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within 6 months of enrollment.
• Implanted pacemaker, defibrillator or deep brain stimulator, other implanted electronic devices in the brain or documented clinically significant arrhythmias.
• Infra-tentorial tumor. 9 Known sensitivity to conductive hydrogels. 10 Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory).
• Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol 12 Pregnant or breast-feeding women. 13 Patients unwilling or unable to comply with the protocol. 14 Patients treated on any other therapeutic clinical protocols within 3 weeks of starting on this study.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• NovoCure Ltd.: collaborator

Study Sites (1)

Ummc Msgcc

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

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; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

Study was terminated due to poor accrual. No analysis was done due to having not met accrual for study analysis.

Results Point of Contact

• Title: Caitlin Eggleston
• Organization: University of Maryland Medical Center

caitlineggleston@umm.edu

4103287586

Study Officials

• Kwok Young, MD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 13, 2013
• First Posted: August 19, 2013
• Study Start: May 1, 2014
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: February 3, 2022
• Results First Posted: February 3, 2022

Record last verified: 2022-01

Locations

US (1)