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

Study ID
STU 032015-041

Study Sites

  • Children’s Medical Center (Dallas, Plano, Southlake)

Contact
Rafael Leon
214/648-1929
Rafael.Leon@UTSouthwestern.edu

Principal Investigator
Edward Pan, M.D.

Official Title

Adult Study: ABT-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 (EORTC Protocol 1410-BTG) Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas

Brief Overview

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.

Description

The pediatric sub-study is an uncontrolled, open-label, single-arm global study. This sub-study is to evaluate the safety, tolerability, and pharmacokinetics of ABT-414 in a pediatric population less than 18 years of age as well as to assess the effect of ABT-414 on tumor response per Response Assessment in Neuro-Oncology (RANO) criteria.

Eligibility

Inclusion Criteria:
Adult participants (greater than or equal to 18 years old):
- Histologically confirmed de novo (primary) Glioblastoma Multiforme 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.
Pediatric sub-study participants (less than 18 years old):
- The study will only include patients under 3 years of age when results of a juvenile repeated mouse toxicity study become available and are favorable to support use in patients aged under 3 years.
- 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.
Exclusion Criteria:
Adult population (greater than or equal to 18 years old):
- Prior treatment with nitrosoureas
- Prior treatment with bevacizumab
- Previous exposure to Epithelial Growth Factor Receptor (EGFR) targeted agents, including EGFRvIII targeting agents
- Prior discontinuation of temozolomide chemotherapy for toxicity reasons
- Prior Radiation Therapy (RT) with a dose over 65 Gy, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven
- 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
- 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.
- No history of wheat allergies and Coeliac disease.
- 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.
Pediatric sub-study (less than 18 years old):
- (For recurrent disease) No prior RT with a dose over 65Gy to the brain, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven
- No current or recent (within 4 weeks or 5 half-lives (whichever is shorter) before enrollment) treatment with another investigational drug
- Female participants 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.