Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas (INTELLANCE 2)

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.

The study includes a Pediatric sub-study to evaluate safety, tolerability and pharmacokinetics of ABT-414 in a pediatric population.

Adult enrollment has been completed and the study is now only recruiting for pediatric participants.

Primary Outcome Measures:

• Adult study: Overall Survival (OS) [ Time Frame: Measured from the date of randomization up to the date of participant's death. Participants who complete treatment will be assessed every 12 weeks, up to 28 months. ]
  • Overall Survival (OS) is defined as number of days from the date of randomization to the date of death for all dosed participants.
• Adult study: Progression Free Survival (PFS) [ Time Frame: PFS will be measured every 8 weeks from date of randomization until the date of first objective progression or participant's death, whichever occurs first, up to 2 years. This will be assessed at interim analysis, when 45 PFS events are observed. ]
  • Progression Free Survival per RANO criteria is the length of time during and after the treatment of a disease, that the participant lives with the disease but does not get worse.
• Pediatric study: Percentage of participants with adverse events [ Time Frame: From participants first visit until 35 days after the participant's last dose of study drug ]
• Pediatric study: Maximum observed serum concentration (Cmax) for ABT-414 [ Time Frame: Samples collected at various time points from Cycle 1 Day 1 up to 35 days after the participant's last dose of study drug ]
  • Cmax is the peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
• Pediatric study: Half-life (t1/2) observed for ABT-414 [ Time Frame: Samples collected at various time points from Cycle 1 Day 1 up to 35 days after the participant's last dose of study drug. ]
  • Half-life is the calculated time it takes for half of the drug to leave the body.
• Pediatric study: Area Under the Concentration-time Curve (AUC) observed for ABT-414 [ Time Frame: Samples collected at various time points from Cycle 1 Day 1 up to 35 days after the participant's last dose of study drug. ]
  • AUC is a measure of how long and how much drug is present in the body after dosing. AUC in pediatric population will be compared following treatment, to check that this is comparable to adults, and the dosing levels are appropriate for a pediatric population.
• Pediatric study: Maximum observed plasma concentration (Cmax) for Cys-mcMMAF (toxin, identified as a metabolite of ABT-414) [ Time Frame: Samples collected Cycle 1 Days 1, 2, 3, 5, 8 ]
  • Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
• Pediatric study: t1/2 for Cys-mcMMAF (toxin, identified as a metabolite of ABT-414) [ Time Frame: Samples collected Cycle 1 Days 1, 2, 3, 5, 8 ]
  • Half-life is the calculated time it takes for half of the drug or drug metabolite to leave the body.
• Pediatric study: AUC for Cys-mcMMAF (toxin, identified as a metabolite of ABT-414) [ Time Frame: Samples collected Cycle 1 Days 1, 2, 3, 5, 8 ]
  • AUC is a measure of how long and how much drug or drug metabolite is present in the body after dosing. AUC in pediatric population will be compared following treatment, to check that this is comparable to adults, and the dosing levels are appropriate for a pediatric population.

Secondary Outcome Measures:

• Adult study: Progression Free Survival (PFS) [ Time Frame: Progression Free Survival will be measured every 8 weeks from date of randomization until the date of first objective progression or date of participant's death, whichever occurs first, assessed up to 28 months. ]
  • Progression Free Survival per RANO criteria is the length of time during and after the treatment of a disease, that the participant lives with the disease but does not get worse.
• Adult study: Overall Response Rate (ORR) [ Time Frame: The overall response rate will be evaluated every 8 weeks at each assessment of disease according to RANO criteria, up to 28 months. ]
  • Overall Response Rate will look at those complete responders and partial responders
• Adult study: Overall Survival in the subgroup with Epithelial Growth Factor Receptor (EGFRvIII) mutation [ Time Frame: Measured from date of randomization until death, or lost to follow up, assessed up to 28 months. ]
  • Overall Survival (OS) is defined as number of days from the date of randomization to the date of death for all randomized participants that have EGFR vIII mutation.
• Pediatric study: Rate of tumor response using RANO criteria (progression of disease [PD], stable disease [SD], partial response [PR], or complete response [CR]). [ Time Frame: Evaluated every 8 weeks at each assessment of disease according to RANO criteria, until progression or withdrawal up to approximately 52 weeks. ]
  • Complete response: All lesions disappeared which includes measurable and non-measurable (improved).
• Partial response: 50% or more decrease in measurable lesions and no progression in non-measurable disease.
  • Stable Disease: Lesions stable or decreasing (stable). Progression of disease: Unequivocal progression (worsening).