ABT-414 alone or ABT-414 plus temozolomide versus temozolomide or lomustine alone in subjects with recurrent glioblastoma.

Recruitment & Eligibility

Status: A

Sex: Not specified

Target Recruitment: 270

Inclusion Criteria

1. Histologically confirmed de novo (primary) GBM with unequivocal tumor progression or recurrence.
2. 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
3. Age = 18 years
4. 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.
5. Availability of adequate biological material (formalin-fixed paraffin embedded [FFPE] tumor) for central testing of EGFR amplification
6. Presence of EGFR amplification confirmed by central assessment; patients with undetermined EGFR status are excluded
7. WHO Performance status 0 - 2
8. No more than one line of chemotherapy for GBM (concurrent and adjuvant TMZ 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
• 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 m2 by modified Schwartz equation for pediatric patients < 12 years of age
• Liver function: Total bilirubin = 1.5 times upper limit of normal (ULN), Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) = 3 times ULN. Subjects with Gilbert's syndrome documented in medical history may be enrolled if total bilirubin is < 3 times ULN.
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 d

Exclusion Criteria

1. Prior treatment with nitrosoureas
2. Prior treatment with bevacizumab
3. Previous exposure to EGFR targeted agents, including EGFRvIII targeting agents
4. Prior discontinuation of temozolomide chemotherapy for toxicity reasons
5. Prior RT with a dose over 65 Gy to 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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Updated 12/10/2019

ABT-414 alone or ABT-414 plus temozolomide versus temozolomide or lomustine alone in subjects with recurrent glioblastoma.

Recruitment & Eligibility

Study & Design

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