INTELLANCE 2: This phase II trial is evaluating ABT414 alone and in combination with chemotherapy for patients with recurrent glioblastomaABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma: A Randomized Phase II Study of the EORTC Brain Tumor Group

Inclusion

Adult participants (greater than or equal to 18 years old):

• Histologically confirmed de novo (primary) glioblastoma with unequivocal tumor progression or recurrence.
• 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
• 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.
• Availability of adequate biological material (formalin-fixed paraffin embedded [FFPE] tumor) for central testing of Epithelial Growth Factor Receptor (EGFR) amplification
• Presence of EGFR amplification confirmed by central assessment; participants with undetermined EGFR status are excluded
• World Health Organization (WHO) Performance status 0 - 2
• 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.
• Post surgery MRI within 48 hours following surgery, however an MRI scan has to be done within 2 weeks prior to randomization.
• Surgery completed at least 2 weeks before randomization and patients should have fully recovered as assessed by investigators.
• Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula.
• Liver function: bilirubin < 1.5× upper limit of the normal range (ULN), alkaline phosphatase and transaminases (ASAT) < 2.5× ULN

Pediatric sub-study participants (less than 18 years old):

• Histologically proven high grade glioma (HGG: WHO grade III glioma [e.g anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma], grade IV glioma [e.g. glioblastoma, gliosarcoma] or diffuse intrinsic pontine glioma [DIPG]).
• Must either have recurrent/progressive tumor or, if newly diagnosed, have completed any planned radiation therapy at least 4 weeks prior to first dose of ABT-414.
• The tumor tissue must have been determined to have EGFR amplification, (by local or other testing service).
• Availability of adequate biological material for retrospective confirmatory central testing of EGFR amplification
• Participant has sufficiently recovered from previous therapy. The investigator believes that benefit of treating the pediatric subject with ABT-414 outweighs the expected risks and that this treatment is in the best interests of the pediatric subject.
• Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula for pediatric patients ≥12 years of age and estimated glomerular filtration rate ≥ 30 mL/min/1.73 m^2 by modified Schwartz equation for pediatric patients < 12 years of age.
• Liver function: Total bilirubin ≤ 1.5× upper limit of the normal range (ULN), Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) <= 3× ULN. Participants with Gilbert's syndrome documented in medical history may be enrolled if total bilirubin is < 3 times ULN. Not allowed are participants with known chronic liver disease and/or cirrhosis.