Study Evaluating ABT-414 in Japanese Subjects With Malignant Glioma

Study Overview
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Brief Summary
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This study seeks to evaluate the tolerability, pharmacokinetics (PK), efficacy, and safety of ABT-414 in Japanese participants with newly diagnosed and recurrent, World Health Organization (WHO) grade III or IV malignant glioma.

Official Title
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A Non-Randomized, Open-Label, Multi-Center Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-414 in Japanese Subjects With Malignant Glioma

Conditions
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Malignant Glioma, Glioblastoma Multiforme

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese participants with WHO grade III or IV malignant glioma 70 or above on Karnofsky Performance Status in Arm A of Phase 1 portion and Phase 2 portion 80 or above on Karnofsky Performance Status in Arm B and Arm C of Phase 1 portion Adequate bone marrow function Recurrent malignant glioma per RANO criteria in Arm A of Phase 1 portion and Phase 2 portion Histologically proven newly diagnosed malignant glioma in Arm B and Arm C of Phase 1 portion Participants must have confirmed EGFR amplification by central lab in Phase 2 portion Exclusion Criteria: Anti-cancer treatment 28 days prior to study Day 1 for Arm A of Phase 1 portion and Phase 2 portion (except temozolomide therapy for newly diagnosed treatment for Phase 2 portion) Anti-cancer treatment prior to study Day 1 for Arm B and Arm C of Phase 1 portion Participant has received prior treatment with bevacizumabor, EGFR therapy in Arm A of Phase 1 portion and Phase 2 portion, or for recurrent glioblastoma in Phase 2 portion Participant has a history of major immunologic reaction to any Immunoglobulin G containing agents or component of ABT-414.

Ages Eligible for Study
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Minimum Age: 20 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 of Phase 1 portion<br>ABT-414 administered every other weeks monotherapy | Drug: ABT-414<br>* ABT-414 will be administered by intravenous infusion<br>* Other names: Mafodotin;|
| Experimental: Phase 2 portion<br>ABT-414 administered every other weeks in combination with temozolomide | Drug: Temozolomide<br>* Temozolomide will be administered per label.<br>Drug: ABT-414<br>* ABT-414 will be administered by intravenous infusion<br>* Other names: Mafodotin;|
| Experimental: Arm C of Phase 1 portion<br>ABT-414 administered every other weeks in combination with radiation and temozolomide | Radiation: Whole Brain Radiation<br>* Whole Brain Radiation will be administered in over 30 fractions as per the procedure in each study site.<br>Drug: Temozolomide<br>* Temozolomide will be administered per label.<br>Drug: ABT-414<br>* ABT-414 will be administered by intravenous infusion<br>* Other names: Mafodotin;|
| Experimental: Arm B of Phase 1 portion<br>ABT-414 administered every other weeks in combination with radiation and temozolomide | Radiation: Whole Brain Radiation<br>* Whole Brain Radiation will be administered in over 30 fractions as per the procedure in each study site.<br>Drug: Temozolomide<br>* Temozolomide will be administered per label.<br>Drug: ABT-414<br>* ABT-414 will be administered by intravenous infusion<br>* Other names: Mafodotin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with adverse events |  | At each visit for approximately 4 years | 
| Number of Dose Limiting Toxicities | Measurement by clinical lab results, vital signs, physical exam and electrocardiogram (ECG) during the Phase 1 portion of the study. | At each visit for approximately 1 year | 
| Progression-free survival | Time to progression-free survival is defined as the number of days from the date of first dose to the date of earliest disease progression based on Response Assessment in Neuro-Oncology (RANO) criteria or to the date of death, if disease progression does not occur (except Arm B and Arm C of Phase 1 portion). | At each visit for approximately 1 year | 
| Area under the plasma concentration-time curve (AUC) of ABT-414 | Assessed during the Phase 1 portion of the study, the area under the plasma concentration-time curve (AUC) is a method of measurement to determine the total exposure of a drug in blood plasma. | Multiple time points in Cycles 1, 2 and 3 (4 weeks each) and Day 1 of remaining cycles until end of treatment for approximately 1 year for recurrent subjects and in every week of Day 1 until Week 7 and end of treatment for the newly diagnosed subjects | 
| Maximum plasma concentration (Cmax) of ABT-414 | Assessed during the Phase 1 portion of the study, the maximum plasma concentration (Cmax) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. | Multiple time points in Cycles 1, 2 and 3 (4 weeks each) and Day 1 of remaining cycles until end of treatment for approximately 1 year for recurrent subjects and in every week of Day 1 until Week 7 and end of treatment for the newly diagnosed subjects | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | The objective response rate is defined as the proportion of participants with at least one measurable lesion at baseline who achieves a confirmed complete (CR) or partial response (PR) based on RANO criteria (except Arm B and Arm C of Phase 1 portion). | At each visit for approximately 1 year | 
| Overall Survival | Overall survival is defined as number of days from the date of first dose to the date of death for all dosed participants (except Arm B and Arm C of Phase 1 portion). | At each visit for approximately 1 year | 
| Duration of Overall Response | The duration of overall response for a given participant is defined as the number of days from the day the RANO criteria are met for CR or PR (whichever is recorded first) to the date that progressive disease (PD) is objectively documented (based RANO criteria) (except Arm B and Arm C of Phase 1 portion). | At each visit for approximately 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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WHO grade III, WHO grade IV, Glioblastoma