Evaluating the Safety and Pharmacokinetics of ABT-414 for Subjects With Glioblastoma Multiforme

Study Overview
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Brief Summary
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This study is evaluating the safety and pharmacokinetics of ABT-414 in subjects with glioblastoma multiforme.

Official Title
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A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-414 for Subjects With Glioblastoma Multiforme

Conditions
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Glioblastoma Multiforme

Intervention / Treatment
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* Drug: ABT-414
* Drug: Temozolomide
* Radiation: Whole Brain Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Glioblastoma Multiforme (GBM) 70 or above on Karnofsky Performance Status Adequate bone marrow function Recurrent GBM per RANO criteria Subjects must have confirmed EGFR amplification by central lab Exclusion Criteria: For Subjects with recurrent GBM in Arm B, subject has received prior treatment with bevacizumab, nitrosourea, or has secondary GBM For Subjects with recurrent GBM in Arm C, subject has received prior treatment with bevacizumab, or has secondary GBM Allergies to temozolomide, dacarbazine, IgG containing agents Anti-cancer treatment 28 days prior to study Day 1, except in Arm B expanded cohort temozolomide therapy is allowed Subjects that have had more than one disease recurrence

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>ABT-414 in combination with radiation and temozolomide | Drug: ABT-414<br>* ABT-414 will be administered by intravenous infusion<br>* Other names: Depatuxizumab Mafodotin;Drug: Temozolomide<br>* Temozolomide will be administered per label and local prescribing regulations.<br>Radiation: Whole Brain Radiation<br>* Whole Brain radiation will be administered in 30 fractions.<br>|
| Experimental: Arm B<br>ABT-414 in combination with temozolomide | Drug: ABT-414<br>* ABT-414 will be administered by intravenous infusion<br>* Other names: Depatuxizumab Mafodotin;Drug: Temozolomide<br>* Temozolomide will be administered per label and local prescribing regulations.<br>|
| Experimental: Arm C<br>ABT-414 monotherapy | Drug: ABT-414<br>* ABT-414 will be administered by intravenous infusion<br>* Other names: Depatuxizumab Mafodotin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and percentage of participants with adverse events | Measurement by clinical lab results, vital signs, physical exam, and electrocardiogram (ECG) | Every week for an expected average of 34 weeks | 
| Maximum concentration of ABT-414 | Measurement of the maximum concentration of ABT- 414 in the blood | Multiple time points in Cycles 1, 2, and 3 (4 weeks each) and Day 1 of remaining cycles until end of treatment, an expected average of 34 weeks | 
| Number of Dose Limiting Toxicities | Measurement by clinical lab results, vital signs, physical exam, and electrocardiogram (ECG) | Every week for an expected average of 34 weeks | 
| Minimum Concentration of ABT-414 | Measurement of the minimum concentration of ABT-414 in the blood | Multiple time points in Cycles 1, 2, and 3 (4 weeks each) and Day 1 of remaining cycles until end of treatment, an expected average of 34 weeks | 
| Half-life of ABT-414 | Measurement of the clearance of ABT-414 | Multiple time points in Cycles 1, 2, and 3 (4 weeks each) and Day 1 of remaining cycles until end of treatment, an expected average of 34 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker EGFR expression | Assessment of tumor biomarkers that may correlate with efficacy. | At screening and post-study | 
| Progression Free Survival | 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. | Multiple time points in each cycle, throughout study, and survival information monthly until 1 year after last visit, or the participant becomes lost to follow up, or study termination. | 
| Overall Survival | The overall response rate will be evaluated every 8 weeks at each assessment of disease according to RANO criteria, up to 28 months | Multiple time points in each cycle, throughout study, and survival information monthly until 1 year after last visit, or participant becomes lost to follow up, or study termination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GBM