A Study of ABT-414 in Participants With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification
- Conditions
- GlioblastomaGliosarcoma
- Interventions
- Registration Number
- NCT02573324
- Lead Sponsor
- AbbVie
- Brief Summary
This study seeks to determine whether the addition of ABT-414 to concomitant radiotherapy and temozolomide (TMZ) followed by combination of ABT-414 with adjuvant TMZ prolongs overall survival (OS) among participants with newly diagnosed glioblastoma (GBM) with epidermal growth factor receptor (EGFR) amplification.
In addition, there is a Phase 1, open-label, multicenter sub-study to assess the pharmacokinetics, safety and tolerability of ABT-414 in participants with newly diagnosed EGFR-amplified GBM who have mild or moderate hepatic impairment.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 691
- Must have a clinical diagnosis of glioblastoma (GBM).
- Must have a confirmed epidermal growth factor receptor amplification in tumor tissue.
- Must have a Karnofsky Performance Status (KPS) >= 70 at assessment <= 14 days prior to randomization (N/A to the sub-study).
- Must have recovered from effects of surgery, postoperative infection and other complications of surgery.
- Must have adequate bone marrow, renal, and hepatic function (For the sub-study, the participant must have adequate bone marrow and renal function and have mild-to-moderate hepatic impairment).
- Multifocal, recurrent or metastatic GBM or gliomatosis cerebri (For the sub-study, the participant can have multifocal GBM and glimatosis cerebri but can't have recurrent or metastatic GBM).
- Prior chemo therapy or radiosensitizer for head and neck cancer.
- Prior radiotherapy to the head or neck in overlap of radiation fields.
- Prior therapy for glioblastoma or other invasive malignancy.
- Prior, concomitant or planned treatment with Novo Tumor Treatment Fields (Novo-TTF), EGFR-targeted therapy, bevacizumab, Gliadel wafers or other intratumoral or intracavity anti-neoplastic therapy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Open-Label Sub-Study: Depatuxizumab Mafodotin, Radiation and TMZ Temozolomide Depatuxizumab mafodotin is given to participants with hepatic impairment on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase. Placebo, Radiation and TMZ Radiation Placebo is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Placebo is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase. Open-Label Sub-Study: Depatuxizumab Mafodotin, Radiation and TMZ Radiation Depatuxizumab mafodotin is given to participants with hepatic impairment on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase. Depatuxizumab Mafodotin, Radiation and Temozolomide (TMZ) Radiation Depatuxizumab mafodotin is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase. Placebo, Radiation and TMZ Placebo for ABT-414 Placebo is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Placebo is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase. Depatuxizumab Mafodotin, Radiation and Temozolomide (TMZ) Temozolomide Depatuxizumab mafodotin is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase. Placebo, Radiation and TMZ Temozolomide Placebo is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Placebo is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase. Open-Label Sub-Study: Depatuxizumab Mafodotin, Radiation and TMZ Depatuxizumab mafodotin Depatuxizumab mafodotin is given to participants with hepatic impairment on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase. Depatuxizumab Mafodotin, Radiation and Temozolomide (TMZ) Depatuxizumab mafodotin Depatuxizumab mafodotin is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6). Time to OS is defined as the number of days from the date of randomization to the date of death due to any cause.
- Secondary Outcome Measures
Name Time Method OS for the Epidermal Growth Factor Receptor (EGFR)vIII-Mutated Tumor Subgroup Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6). Time to OS is defined as the number of days from the date of randomization to the date of death due to any cause.
Progression-Free Survival (PFS) Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6). PFS will be defined as the number of days from the date of randomization to the date of earliest disease progression based on Response Assessment in Neuro-Oncology (RANO) criteria (see Wen et al. J Clin Oncol. 2010 Apr 10;28(11):1963-72) or to the date of death, if disease progression does not occur.
PFS for EGFRvIII-Mutated Tumor Subgroup Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6). PFS will be defined as the number of days from the date of randomization 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.
Deterioration Free Survival in M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) Symptom Severity Score Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6). The MDASI-BT assesses the severity of multiple brain tumor-related symptoms and the impact of these symptoms on daily functioning in the last 24 hours. It consists of 22 symptom items and 6 interference items, each rated from 0 to 10. MDASI-BT symptom severity score is defined as average over 13 core symptom items and 9 brain tumor symptom items, with a total score of 0 to 10, with higher score indicating worse symptoms/interference. Changes in symptom severity score were classified into 3 categories: improved (≤ -1), stable (\> -1 and \< 1), and deteriorated (≥ 1). Deterioration is defined as satisfying the deterioration criteria (i.e., increase in symptom severity score by ≥ 1 unit) without further improvement (i.e., failing to satisfy deterioration criteria) within 8 weeks or occurrence of death.
Deterioration Free Survival in MDASI-BT Symptom Interference Score Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6). The MDASI-BT assesses the severity of multiple brain tumor-related symptoms and the impact of these symptoms on daily functioning in the last 24 hours. It consists of 22 symptom items and 6 interference items, each rated from 0 to 10. MDASI-BT symptom interference score is defined as an average of 6 interference items, with a total score of 0 to 10, where higher scores indicate worse interference. Changes in symptom interference score were classified into 3 categories: improved (≤ -1), stable (\> -1 and \< 1), and deteriorated (≥ 1). Deterioration is defined as satisfying the deterioration criteria (i.e., increase in symptom interference score by ≥ 1 unit) without further improvement (i.e., failing to satisfy deterioration criteria) within 8 weeks or occurrence of death.
Deterioration Free Survival in Neurocognitive Functioning on the Hopkins Verbal Learning Test Revised (HVLT-R) Total Recall Score Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6). The HVLT-R consists of 3 parts. Free call has a range of 0 to 36, delayed recall has a range from 0 to 12, and delayed recognition has a range of -12 to 12. Higher scores indicating better function in all 3 parts. When scoring the HVLT-R, the 3 learning trials are combined to calculate a total recall score (range -12 to 60). Deterioration is defined as satisfying the deterioration criteria (i.e., decrease in HVLT-R total recall score by 5 units) without further improvement within 8 weeks or occurrence of death.
OS for the MGMT Methylated Group Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6). Time to OS is defined as the number of days from the date of randomization to the date of death due to any cause.
OS for the O6-methylguaninemethlytransferese (MGMT) Unmethylated Group Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6). Time to OS is defined as the number of days from the date of randomization to the date of death due to any cause.
Unmethylated MGMT promoter is associated with a worse prognosis in GBM
Trial Locations
- Locations (212)
St. Josephs Hospital and Med Center /ID# 144149
🇺🇸Phoenix, Arizona, United States
Highlands Oncology Group, PA /ID# 142050
🇺🇸Springdale, Arkansas, United States
University of Southern California /ID# 147543
🇺🇸Los Angeles, California, United States
University of California, Los Angeles /ID# 149239
🇺🇸Los Angeles, California, United States
Sharp Memorial Hospital /ID# 148193
🇺🇸San Diego, California, United States
Univ California, San Francisco /ID# 145889
🇺🇸San Francisco, California, United States
Duplicate_St. John's Health Center /ID# 148192
🇺🇸Santa Monica, California, United States
Cedars-Sinai Medical Center-West Hollywood /ID# 148472
🇺🇸West Hollywood, California, United States
Univ of Colorado Cancer Center /ID# 148194
🇺🇸Aurora, Colorado, United States
Associated Neurologists of Sou /ID# 147701
🇺🇸Fairfield, Connecticut, United States
Scroll for more (202 remaining)St. Josephs Hospital and Med Center /ID# 144149🇺🇸Phoenix, Arizona, United States