ABT-414 Alone or ABT-414 Plus Temozolomide Versus Temozolomide or Lomustine for Recurrent Glioblastoma: A Randomized Phase 2 Study of the EORTC Brain Tumor Group

This study is to evaluate the efficacy and safety of ABT-414 alone or with temozolomide versus temozolomide or lomustine alone in participants with recurrent glioblastoma multiforme.
Phase 2
Neuroscience - Brain Tumor, Neuroscience
Tara Benkers, MD

Inclusion Criteria:

  1. Histologically confirmed de novo (primary) Glioblastoma Multiforme with unequivocal tumor progression or recurrence. 

    o In case of testing at the time of first progression: either at least 3 months after the end of radiotherapy or have tumor progression that is clearly outside the radiation field or have tumor progression unequivocally proven by surgery/biopsy

  2. Absence of any psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule; such conditions should be assessed with the patient before registration in the trial.
  3. Availability of adequate biological material (formalin-fixed paraffin embedded [FFPE] tumor) for central testing of Epithelial Growth Factor Receptor (EGFR) amplification
  4. Presence of EGFR amplification confirmed by central assessment; patients with undetermined EGFR status are excluded
  5. World Health Organization (WHO) Performance status 0 - 2
  6. No more than one line of chemotherapy (concurrent and adjuvant Temozolomide based chemotherapy including in combination with another investigational agent is considered one line of chemotherapy). Chemotherapy must have been completed at least 4 weeks prior to randomization.
  7. Post surgery MRI within 48 hours following surgery, however an MRI scan has to be done within 2 weeks prior to randomization.
  8. Surgery completed at least 2 weeks before randomization and patients should have fully recovered as assessed by investigators.

Exclusion Criteria:

  1. Prior treatment with nitrosoureas
  2. Prior treatment with bevacizumab
  3. Previous exposure to Epithelial Growth Factor Receptor (EGFR) targeted agents, including EGFRvIII targeting agents
  4. Prior discontinuation of temozolomide chemotherapy for toxicity reasons
  5. Prior Radiation Therapy (RT) with a dose over 65 Gy, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven
  6. Previous other malignancies, except for any previous malignancy which was treated with curative intent more than 5 years prior to randomization, and except for adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of the skin or carcinoma in situ of the cervix
  7. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization.
  8. No history of wheat allergies and Coeliac disease.
  9. No EIAED, patients who require anti-convulsant therapy must be taking non-enzyme inducing antiepileptic drugs (non-EIAED). Patients previously on EIAED must be fully switched to non-EIAED at least 2 weeks prior to randomization.

Mary Lessig