Glioblastoma Grade 4 Brain tumor
Conditions
Interventions
Patients receive one of the following treatments:
Arm 1: patients will be treated with ABT-414 1.25 mg/kg IV infusion over 30 to
40 minutes once every 2 weeks in combination with TMZ 150 mg/m2 day 1
Sponsors
AbbVie B.V.
Eligibility
Age
2 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. 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. 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 for GBM (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.;Pediatric sub-study: • Subject must either have recurrent/progressive tumor or, if newly diagnosed, have completed radiation therapy at least 4 weeks prior to first dose of ABT-414. • The investigator must confirm that the subject is able to complete the procedures required in order to assess the primary endpoints, including PK blood draws and safety assessments over the first four weeks of therapy including Day 1 of Week 5. • The investigator believes that the potential 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. • Subjects and/or their legal guardians must be able to understand the risks and potential benefits, and grant assent/consent to participate by signing the applicable pediatric-specific informed assent and/or consent forms. • Subject has sufficiently recovered from previous therapy. • (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
Exclusion criteria
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 and participation to placebo controlled trials on EGFR targeted agents. 4. Prior discontinuation of temozolomide chemotherapy for toxicity reasons. 5. Prior Radiation Therapy (RT) with a dose over 65 Gy in the brain, 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.;Pediatric substudy: Not allowed are subjects with known chronic liver disease and/or cirrhosis documented by the presence of one or more of the following (assessments to be performed per standard of care only if liver disease is suspected): - Liver biopsy with histologic findings consistent with cirrhosis - CT or US evidence of liver disease with or without portal hypertension - Physical examination and clinical and laboratory evidence of chronic liver disease - Colloid shift on a liver-spleen scan - A Child-Pugh score of 6 or higher • Female subjects 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 enrollment. • Male subjects that are sexually active with female partner(s) of childbearing potential must agree to use an effective method of contraception from Study Day 1, during the treatment period and for at least 6 months after the last study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint will be OS at final analysis and Progression Free Survival (PFS) according to RANO criteria at the interim analysis. Pediatric sub-study - Safety including toxicities according to CTCAE criteria (Percentage of subjects with adverse events from subject's first visit until 49 days after the subject's last dose of study drug) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints will be: * PFS according to RANO criteria and assessed by IRC and local investigators * Objective response % (ORR) * OS in the subgroup with EGFRvIII mutation The following are exploratory endpoints: * Best overall response % (BOR), complete response % (CRR), duration of response (DR) assessed by IRC and local investigators will be computed in each arm * PFS in the subgroup with EGFRvIII mutation * Neurological deterioration-free survival (NDFS) * Steroid use * Frequencies and percentages of Adverse Events (AEs) * Quality of life Pediatric sub-study - Objective response rate, best response rate, and duration of response based on RANO criteria - Overall survival, Time to Progression, and Time to progression-free survival - Changes in neurological status and functioning (including PedsQL cancer module) | — |
Countries
Netherlands
Outcome results
None listed