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.

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.

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.

Adverse events were collected following initiation of treatment until 2 months after treatment termination, an average of 24 months.