Glioblastoma Multiforme, Malignant Glioma
Conditions
Keywords
WHO grade III, WHO grade IV, Glioblastoma
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.
Interventions
RADIATIONWhole Brain Radiation
Whole Brain Radiation will be administered in over 30 fractions as per the procedure in each study site.
DRUGTemozolomide
Temozolomide will be administered per label.
DRUGABT-414
ABT-414 will be administered by intravenous infusion
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 99 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration (Cmax) 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 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. |
| Number of Dose Limiting Toxicities | 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 | 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). |
| Area under the plasma concentration-time curve (AUC) 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 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. |
| Percentage of participants with adverse events | At each visit for approximately 4 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | At each visit for approximately 1 year | 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). |
| Duration of Overall Response | At each visit for approximately 1 year | 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). |
| Objective Response Rate | At each visit for approximately 1 year | 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). |
Countries
Japan
Outcome results
None listed