Clinical Trials /

NovoTTF-100A With Bevacizumab (Avastin) in Patients With Recurrent Glioblastoma

NCT01894061

Description:

NovoTTF-100A is a device and Bevacizumab is a study drug that have both been approved by the FDA (Food and Drug Administration) for use as monotherapy in treating glioblastoma multiforme. The NovoTTF-l00A is a portable battery operated device which produces TTFields within the human body using surface electrodes (transducer arrays). Intermediate frequency electric fields (TTFields) stunt the growth of tumor cells. The purpose of this study is to determine the efficacy of the combination of Bevacizumab and NovoTTF-100A in Bevacizumab naive (meaning have never received bevacizumab before) patients with recurrent glioblastoma (GBM) as measured by 6-month progression free survival.

Related Conditions:
  • Glioblastoma
  • Gliosarcoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: NovoTTF-100A With Bevacizumab (Avastin) in Patients With Recurrent Glioblastoma
  • Official Title: A Prospective Phase II Trial of NovoTTF-100A With Bevacizumab (Avastin) in Patients With Recurrent Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: CASE3313
  • SECONDARY ID: P30CA043703
  • NCT ID: NCT01894061

Conditions

  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor

Interventions

DrugSynonymsArms
BevacizumabAvastin, anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, anti-VEGF rhuMAb, recombinant humanized anti-VEGF monoclonal antibody, rhuMAb VEGFBevacizumab and NovoTTF-100A

Purpose

NovoTTF-100A is a device and Bevacizumab is a study drug that have both been approved by the FDA (Food and Drug Administration) for use as monotherapy in treating glioblastoma multiforme. The NovoTTF-l00A is a portable battery operated device which produces TTFields within the human body using surface electrodes (transducer arrays). Intermediate frequency electric fields (TTFields) stunt the growth of tumor cells. The purpose of this study is to determine the efficacy of the combination of Bevacizumab and NovoTTF-100A in Bevacizumab naive (meaning have never received bevacizumab before) patients with recurrent glioblastoma (GBM) as measured by 6-month progression free survival.

Detailed Description

      This will be an open label Phase II trial in adults with recurrent glioblastoma (GBM). The
      NovoTTF-100A treatment and Bevacizumab will be administered on an outpatient basis;
      NovoTTF-100A treatment will be initiated in the outpatient clinic.

      PRIMARY OBJECTIVES:

      I. To determine the efficacy of the combination of bevacizumab and NovoTTF-100A in
      bevacizumab-naive patients with recurrent glioblastoma (GBM) as measured by 6-month
      progression-free survival (PFS6).

      SECONDARY OBJECTIVES:

      I. To assess safety and tolerability of the combination of bevacizumab and Novo-TTF-100A in
      this patient population.

      II. To evaluate overall survival in this population. III. To determine objective response
      rate (ORR) by modified Revised Assessment in Neuro-Oncology (RANO) criteria in this
      population.

      IV. To assess time-to-progression in this population. V. To assess neurocognitive function
      (NCF) and quality of life (QOL) in this population.

      OUTLINE:

      Patients receive bevacizumab intravenously (IV) on days 1 and 15. Patients also undergo
      electric field therapy with NovoTTF-100A for at least 18 hours daily. Courses repeat every 28
      days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for at least 28 days.
    

Trial Arms

NameTypeDescriptionInterventions
Bevacizumab and NovoTTF-100AExperimentalBevacizumab will be administered intravenously on days 1 and 15 of each 28 day cycle.The dose of bevacizumab will be 10 mg/kg of actual body weight.
  • Bevacizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with histologically confirmed glioblastoma or other grade IV malignant glioma
             (i.e. gliosarcoma, small cell glioblastoma, etc.), recurrent after prior external-beam
             fractionated radiotherapy and temozolomide chemotherapy.

          -  Patients with up to two prior recurrences are allowed.

          -  Karnofsky performance status ≥70.

          -  Patients must have the following laboratory values:

               -  Absolute neutrophil count (ANC) ≥1.5 x 10^9/L

               -  Platelets ≥ 100 x 10^9/L

               -  Hemoglobin (Hgb) > 9 g/dL

               -  Serum total bilirubin: ≤ 1.5 x ULN

               -  ALT and AST ≤ 3.0 x ULN

               -  Serum creatinine ≤ 1.5 x ULN

               -  Blood coagulation parameters: INR ≤ 1.5

          -  Minimum interval since completion of radiation treatment is 12 weeks

          -  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.

          -  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. The effects of
             bevacizumab on developing fetus or nursing infant are not known. Female patients of
             child-bearing potential must have a negative pregnancy test.

          -  Patients must have no concurrent malignancy except curatively treated basal or
             squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast,
             adequately treated stage I or II cancer from which the patient is in complete
             remission. Patients with other prior malignancies must be disease-free for ≥ three
             years.

          -  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.

        Exclusion Criteria:

          -  Patients who have had previous treatment with bevacizumab, and or NovoTTF 100A system.

          -  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 systolic blood pressure (SBP) ≥ 160 mm Hg
                  or diastolic blood pressure (DBP) ≥ 100 mm Hg while on anti-hypertensive
                  medications)

          -  Patients with cirrhosis, or active viral or nonviral hepatitis.

          -  Implanted pacemaker, defibrillator or deep brain stimulator, other implanted
             electronic devices in the brain or documented clinically significant arrhythmias.

          -  Infra-tentorial tumor

          -  Evidence of increased intracranial pressure (clinically significant papilledema,
             vomiting and nausea or reduced level of consciousness)

          -  Known sensitivity to conductive hydrogels

          -  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

          -  Pregnant or breast-feeding women

          -  Patients unwilling or unable to comply with the protocol

          -  Patients with leptomeningeal disease
      
Maximum Eligible Age:N/A
Minimum Eligible Age:22 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:6 months
Safety Issue:
Description:Number of patients that achieve progression free survival by Kaplan Meier methodology.

Secondary Outcome Measures

Measure:Objective response rate based on RANO Criteria
Time Frame:30 days after treatment completion
Safety Issue:
Description:Response will be scored based on a combination of imaging and clinical features as defined by the modified Response Assessment in Neuro-Oncology (RANO) criteria. http://www.iconplc.com/services/imaging/central-imaging-core-lab-/regulatory-expertise/IMI-RANO-Criteria-Booklet-Nov-2011.pdf
Measure:Number of patients that experience toxicities with this combination of therapies
Time Frame:30 days after treatment completion
Safety Issue:
Description:Safety and tolerability of combination of bevacizumab and NovoTTF-l00A in this population by CTCAE version 4.0.
Measure:Median overall survival
Time Frame:30 days after treatment completion
Safety Issue:
Description:
Measure:To assess time-to-progression
Time Frame:30 days after treatment completion
Safety Issue:
Description:Median time to progression by Kaplan Meier methodology.
Measure:Neurocognitive function (NCF)
Time Frame:30 days after treatment completion
Safety Issue:
Description:Time to reliable change (decline) in neurocognitive function by Kaplan Meier methodology. Memory, verbal fluency, visual-motor speed, executive function and motor dexterity tests will be administered.
Measure:Quality of Life (QOL)
Time Frame:30 days after treatment completion
Safety Issue:
Description:Based on the Functional Assessment of Cancer Therapy including Brain Tumor module (FACT-Br) questionnaire

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Case Comprehensive Cancer Center

Trial Keywords

  • adult giant cell glioblastoma
  • adult glioblastoma
  • adult gliosarcoma
  • recurrent adult brain tumor
  • Bevacizumab-naive
  • NovoTTF-100A

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