Clinical Trials /

Study Of NOVOTTF-200A In Bevacizumab-Naive Subjects With Recurrent Grade III Malignant Astrocytoma

NCT03450850

Description:

This is a Phase 2 study in subjects with WHO Grade III Anaplastic Astrocytoma (G3 astrocytoma) who had progressive disease during first or second line treatment and who have not previously received any BEV or any experimental agents.

Related Conditions:
  • Astrocytoma
Recruiting Status:

Not yet recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Study Of NOVOTTF-200A In Bevacizumab-Naive Subjects With Recurrent Grade III Malignant Astrocytoma
  • Official Title: Phase II, Single Arm Study Of NOVOTTF-200A In Bevacizumab-Naive Subjects With Recurrent WHO Grade III Malignant Astrocytoma

Clinical Trial IDs

  • ORG STUDY ID: UCI 16-56
  • SECONDARY ID: UCI 16-56
  • SECONDARY ID: 2017-4031
  • NCT ID: NCT03450850

Conditions

  • Astrocytoma, Grade III

Purpose

This is a Phase 2 study in subjects with WHO Grade III Anaplastic Astrocytoma (G3 astrocytoma) who had progressive disease during first or second line treatment and who have not previously received any BEV or any experimental agents.

Detailed Description

      Primary Objective:

      The primary objective will be to determine the efficacy of NOVOTTF-200A in recurrent
      anaplastic astrocytoma patients (6-month progression-free survival)

      Secondary Objectives:

        -  To evaluate the safety of NOVOTTF-200A in the subject population.

        -  To evaluate efficacy of NOVOTTF-200A in the subject population.

        -  To see if the presence of ATRX, TERT promoter, IDH1 mutations and/or MGMT promoter
           methylation, confers a better response to NOVOTTF-200A.

        -  To determine if the treatment significantly modifies the patient's quality of life.
           Sponsor will use the Functional Assessment of Cancer Therapy (FACT) questionnaires:

             -  FACT-Brain (FACT-Br)

             -  FACT-Cognitive Function (FACT-Cog)

      Exploratory Objectives:

        -  To determine if the presence of proneural or mesenchymal phenotype (Cytoscan analysis)
           confers a better response to NovoTTF.

        -  To determine if the in vitro sensitivity of the glioma cells derived from patient
           specimens before and after the NOVOTTF-200A treatment correlates with the patient's
           response to treatment.
    

Trial Arms

NameTypeDescriptionInterventions
NOVOTTF-200AOtherNOVOTTF-200A treatment in Bevacizumab-Naïve Subjects with Recurrent WHO Grade III Malignant Astrocytoma

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Understand and voluntarily sign and date an informed consent document before any study
                 related assessments/procedures are conducted.
    
              2. Males and females of age ≥18 years at the time of the signing of the informed consent
                 document.
    
              3. All subjects must have histologic evidence of G3 MG and radiographic evidence of
                 recurrence or disease progression (defined as either a greater than 25% increase in
                 the largest bi-dimensional product of enhancement, a new enhancing lesion or a
                 significant increase in T2 FLAIR).
    
              4. Subjects with archival tumor tissue suitable for genetic testing must give permission
                 to access and test the tissue; subjects without archival tumor tissue are eligible.
    
              5. No prior treatment with BEV or any anti-angiogenesis agents.
    
              6. At least 4 weeks from surgical resection and 12 weeks from end of radiotherapy prior
                 to enrollment in this study, unless relapse is confirmed by tumor biopsy or new lesion
                 outside of radiation field, or if there are two MRIs confirming progressive disease
                 that are 8 weeks apart.
    
              7. All AEs resulting from prior chemotherapy, surgery or radiotherapy must have resolved
                 to NCI-CTCAE (v. 4.03) Grade ≤1 (except for laboratory parameters outlined below).
    
              8. Laboratory results within 7 days prior to NOVOTTF-200A administration (transfusions
                 and/or growth factor support may be used at the discretion of the Investigator during
                 Screening):
    
                   -  Hemoglobin ≥9 g/dL.
    
                   -  Absolute neutrophil count (ANC) ≥1.5 × 109/L.
    
                   -  Platelet count ≥100 × 109/L.
    
                   -  Serum bilirubin ≤1.5 × upper limit of normal (ULN) or ≤3 × ULN if Gilbert's
                      disease is documented.
    
                   -  Aspartate transaminase (AST) ≤ 2.5 ULN.
    
                   -  Serum creatinine ≤1.5 × ULN.
    
              9. Karnofsky Performance Status (KPS) score ≥70%.
    
             10. Willing and able to adhere to the study visit schedule and other protocol
                 requirements.
    
            Exclusion Criteria:
    
            The presence of any of the following will exclude a subject from enrollment:
    
              1. The presence of 1p19q LOH which is diagnostic for anaplastic oligodendroglioma (AO).
    
              2. Co-medication that may interfere with study results, e.g., immunosuppressive agents
                 other than corticosteroids. (Steroid therapy for control of cerebral edema is allowed
                 at the discretion of the investigator. Subjects should be on a stable dose of steroids
                 for at least 1 week prior to study beginning.)
    
              3. Chemotherapy administered within 4 weeks (6 weeks for an IV nitrosoureas and 12 weeks
                 for an implanted nitrosoureas wafer) prior to Day 1 of study treatment.
    
              4. Pregnancy or breastfeeding.
    
              5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
                 infection requiring IV antibiotics & psychiatric illness/social situations that would
                 limit adherence with study requirements, or disorders associated with significant
                 immunocompromised state.
    
              6. Known previous/current malignancy requiring treatment within ≤ 3 years except for
                 cervical carcinoma in situ, squamous or basal cell skin carcinoma and superficial
                 bladder carcinoma.
    
              7. Any comorbid condition that confounds the ability to interpret data from the study as
                 judged by the Investigator.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:22 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Number of participants showing no evidence of disease progression six months after initiating treatment with the device.
    Time Frame:6 months
    Safety Issue:
    Description:The primary objective is to estimate the proportion of participants showing no evidence of disease progression six months after initiating treatment with the device. Assessment is per RANO (2010) criteria.

    Secondary Outcome Measures

    Measure:Evaluation of the safety of NOVOTTF-200A in this subject population.
    Time Frame:1 year
    Safety Issue:
    Description:All subjects will be evaluated for safety analysis if they receive NOVOTTF-200A. Safety and tolerability of NOVOTTF-200A treatment will be based on the incidence and severity of adverse events and toxicities. Toxicities will be assessed according to the "Common toxicity criteria (CTC), version 4.03".
    Measure:Does the treatment significantly modify the patient's quality of life?
    Time Frame:Will be assessed at baseline and every two cycles (at the end of each even-numbered cycle of therapy) until treatment termination, an average of 24 months
    Safety Issue:
    Description:To determine if the treatment significantly modifies the patient's quality of life we will be using the Functional Assessment of Cancer Therapy (FACT) questionnaires that include the FACT-Brain (FACT-Br), and the FACT-Cognitive Function (FACT-Cog) questionnaires. These will be completed at baseline then every two cycles.
    Measure:Correlations with established molecular markers (ATRX, TERT promoter and/or IDH1 mutation and MGMT promoter methylation
    Time Frame:Will be assessed at screening and at end of treatment visit, an average of 24 months
    Safety Issue:
    Description:To see if the presence of ATRX, TERT promoter, IDH1 mutations and/or MGMT promoter methylation, confers a better response to NOVOTTF-200A.

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Daniela A. Bota

    Last Updated

    February 26, 2018