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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 53
- Locations
- 22
- Primary Endpoint
- Area under the plasma concentration-time curve (AUC) of ABT-414
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to 99 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Arm A of Phase 1 portion
ABT-414 administered every other weeks monotherapy
Intervention: ABT-414 (Drug)
Phase 2 portion
ABT-414 administered every other weeks in combination with temozolomide
Intervention: Temozolomide (Drug)
Phase 2 portion
ABT-414 administered every other weeks in combination with temozolomide
Intervention: ABT-414 (Drug)
Arm C of Phase 1 portion
ABT-414 administered every other weeks in combination with radiation and temozolomide
Intervention: Whole Brain Radiation (Radiation)
Arm C of Phase 1 portion
ABT-414 administered every other weeks in combination with radiation and temozolomide
Intervention: Temozolomide (Drug)
Arm C of Phase 1 portion
ABT-414 administered every other weeks in combination with radiation and temozolomide
Intervention: ABT-414 (Drug)
Arm B of Phase 1 portion
ABT-414 administered every other weeks in combination with radiation and temozolomide
Intervention: Whole Brain Radiation (Radiation)
Arm B of Phase 1 portion
ABT-414 administered every other weeks in combination with radiation and temozolomide
Intervention: Temozolomide (Drug)
Arm B of Phase 1 portion
ABT-414 administered every other weeks in combination with radiation and temozolomide
Intervention: ABT-414 (Drug)
Outcomes
Primary Outcomes
Area under the plasma concentration-time curve (AUC) of ABT-414
Time Frame: 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
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.
Maximum plasma concentration (Cmax) of ABT-414
Time Frame: 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
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.
Percentage of participants with adverse events
Time Frame: At each visit for approximately 4 years
Number of Dose Limiting Toxicities
Time Frame: At each visit for approximately 1 year
Measurement by clinical lab results, vital signs, physical exam and electrocardiogram (ECG) during the Phase 1 portion of the study.
Progression-free survival
Time Frame: At each visit for approximately 1 year
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).
Secondary Outcomes
- Objective Response Rate(At each visit for approximately 1 year)
- Duration of Overall Response(At each visit for approximately 1 year)
- Overall Survival(At each visit for approximately 1 year)