Description:
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.
Title
- Brief Title: A Study of ABT-414 in Participants With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification
- Official Title: A Randomized, Placebo Controlled Phase 3 Study of ABT-414 With Concurrent Chemoradiation and Adjuvant Temozolomide in Subjects With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification (Intellance1)
Clinical Trial IDs
- ORG STUDY ID:
M13-813
- SECONDARY ID:
2015-001166-26
- NCT ID:
NCT02573324
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Temozolomide | | ABT-414, Radiation and Radiation/Temozolomide (TMZ) |
| ABT-414 | Depatuxizumab, Mafodotin | ABT-414, Radiation and Radiation/Temozolomide (TMZ) |
| Placebo for ABT-414 | | Placebo, Radiation and TMZ |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| ABT-414, Radiation and Radiation/Temozolomide (TMZ) | Experimental | ABT-414 is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. ABT-414 is given on Day 1 & 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 Comparator | 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 & 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase. | - Temozolomide
- Placebo for ABT-414
|
Eligibility Criteria
Inclusion Criteria:
- 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).
Exclusion Criteria:
- Multifocal, recurrent or metastatic Glioblastoma (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.
| Maximum Eligible Age: | 99 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Overall Survival (OS) |
| Time Frame: | Quarterly After Treatment Discontinuation for Approximately 4 Years |
| Safety Issue: | |
| Description: | 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
| Measure: | Progression-Free Survival (PFS) |
| Time Frame: | Baseline Day 0 Through Approximately 4 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | OS for the O6-methylguaninemethlytransferese (MGMT) Unmethylated Group |
| Time Frame: | Baseline Day 0 Through Approximately 4 years |
| Safety Issue: | |
| Description: | Time to OS is defined as the number of days from the date of randomization to the date of death due to any cause. |
| Measure: | OS for the MGMT Methylated Group |
| Time Frame: | Baseline Day 0 Through Approximately 4 years |
| Safety Issue: | |
| Description: | Time to OS is defined as the number of days from the date of randomization to the date of death due to any cause. |
| Measure: | Time to Deterioration in Symptom Severity Score M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) |
| Time Frame: | Baseline Day 0 Through Approximately 4 years |
| Safety Issue: | |
| Description: | The MDASI-BT is a participant self-report or interviewer-administered measure used to assess the severity of multiple brain tumor-related symptoms and the impact of these symptoms on daily functioning in the last 24 hours. |
| Measure: | Time to Deterioration in Symptom Interference Score MDASI-BT |
| Time Frame: | Baseline Day 0 Through Approximately 4 years |
| Safety Issue: | |
| Description: | The MDASI-BT is a participant self-report or interviewer-administered measure used to assess the severity of multiple brain tumor-related symptoms and the impact of these symptoms on daily functioning in the last 24 hours. |
| Measure: | Time to Deterioration in Neurocognitive Functioning on the Hopkins Verbal Learning Test Revised (HVLT-R) |
| Time Frame: | Baseline Day 0 Through Approximately 4 years |
| Safety Issue: | |
| Description: | The HVLT-R will assess neurocognitive changes across time. |
| Measure: | OS for the Epidermal Growth Factor Receptor (EGFR)vIII-Mutated Tumor Subgroup |
| Time Frame: | Baseline Day 0 Through Approximately 4 years |
| Safety Issue: | |
| Description: | Time to OS is defined as the number of days from the date of randomization to the date of death due to any cause. |
| Measure: | PFS for EGFRvIII-Mutated Tumor Subgroup |
| Time Frame: | Baseline Day 0 Through Approximately 4 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Number of Adverse Events (AE) |
| Time Frame: | Baseline Day 0 Through Approximately 4 years |
| Safety Issue: | |
| Description: | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. |
Details
| Phase: | Phase 2/Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | AbbVie |
Trial Keywords
- Newly Diagnosed Glioblastoma
- Epithelial Growth Factor Receptor (EGFR)
- Temozolomide
- ABT-414
- Radiology Therapy Oncology Group
- Antibody Drug Conjugate
- Brain Tumor
- Brain Tumor Group
- EGFRvIII
- EGFR Amplified
- First Line Therapy
- Brain Cancer
Last Updated
May 24, 2021
