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

NCT01925573

Description:

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.

Related Conditions:
  • Glioblastoma
  • Gliosarcoma
Recruiting Status:

Active, not recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Optune(NOVOTTF-100A)+ Bevacizumab+ Hypofractionated Stereotactic Irradiation Bevacizumab-Naive Recurrent Glioblastoma (GCC 1344)
  • Official Title: Proposed Pilot Study of Combined Optune+ Bevacizumab, and Hypofractionated Stereotactic Irradiation for Bevacizumab-Naive Recurrent Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: HP-00056719
  • NCT ID: NCT01925573

Conditions

  • RECURRENT GLIOBLASTOMA
  • Brain Tumor

Purpose

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.

Detailed Description

      The combination of Optune(NovoTTF) with the active regimen of bevacizumab and
      hypofractionated stereotactic radiotherapy bases the addition of an effective new treatment
      in the setting of a safe regimen with favorable survival reports. To date, no clinical data
      are available on the interaction of concomitant tumor treating fields with radiation therapy
      either with or without bevacizumab. TTF and radiation both have the potential to enhance the
      other's therapeutic ratio though synergistic mechanisms of action. The addition of
      bevacizumab to this regimen has both therapeutic and improved-toxicity implications. A trial
      combining Optune with the proven regimen of HFSRT and bevacizumab for recurrent glioblastoma
      affords an avenue to demonstrate safety in a population who may more readily derive a
      benefit from novel multimodality therapy and explore the potential for synergistic effect.
      The endpoint of efficacy would clearly need to be more definitively addressed in a future
      categorical trial, which would be the logical positive outcome of this pilot study.
    

Trial Arms

NameTypeDescriptionInterventions
Optune+RT+BevacuzimabOtherPart 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

    Eligibility Criteria

            Inclusion Criteria:
    
              -  1 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.
    
                 2 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.
    
                      9 Minimum interval since last major surgery, open biopsy, or significant
                      traumatic injury is 4 weeks 10 Minimum interval since last drug therapy:
    
                   -  3 weeks since last non-cytotoxic therapy
    
                   -  3 weeks must have elapsed since the completion of a non-nitrosourea-containing
                      chemotherapy regimen
    
                   -  6 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.
    
                      12 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.
    
                      13 Patients with history of prior invasive malignancy (except non-melanomatous
                      skin cancer) must have been disease free for a minimum of 1 year.
    
                      14 Patients must be maintained on a stable corticosteroid regimen from the time
                      of their baseline scan until the start of treatment and/or for at least 5 days
                      before starting treatment.
    
                      15 Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must
                      meet both of the following criteria: 16 No active bleeding or pathological
                      condition that carries a high risk of bleeding (e.g., tumor involving major
                      vessels or known varices) 17 In-range INR (max ≤ 3) on a stable dose of oral
                      anticoagulant for greater than 1 month or on a stable dose of low molecular
                      weight heparin
    
            Exclusion Criteria:
    
              -  1 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.
    
                 3 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.
    
                 4 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.
    
                      7 Implanted pacemaker, defibrillator or deep brain stimulator, other implanted
                      electronic devices in the brain or documented clinically significant
                      arrhythmias.
    
                      8 Infra-tentorial tumor. 9 Known sensitivity to conductive hydrogels. 10 Known
                      diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not
                      mandatory).
    
                      11 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.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:22 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Number of Adverse Events with a grade 3 or high toxicity (Primary Measure)
    Time Frame:6 months
    Safety Issue:
    Description: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.

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:University of Maryland

    Trial Keywords

    • RECURRENT GLIOBLASTOMA
    • Brain Tumor

    Last Updated

    March 29, 2017