Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of ABT-414 in Participants With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification (Intellance1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02573324
Recruitment Status : Completed
First Posted : October 9, 2015
Results First Posted : May 11, 2023
Last Update Posted : May 11, 2023
Sponsor:
Collaborator:
Radiation Therapy Oncology Group
Information provided by (Responsible Party):
AbbVie

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.


Condition or disease Intervention/treatment Phase
Glioblastoma Gliosarcoma Drug: Temozolomide Drug: Depatuxizumab mafodotin Radiation: Radiation Drug: Placebo for ABT-414 Phase 3

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 691 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Sub-study was open-label.
Primary Purpose: Treatment
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)
Actual Study Start Date : January 4, 2015
Actual Primary Completion Date : April 4, 2022
Actual Study Completion Date : April 4, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Depatuxizumab Mafodotin, Radiation and Temozolomide (TMZ)
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.
 Drug: Temozolomide
Oral Capsule

Drug: Depatuxizumab mafodotin
Intravenous (IV) Infusion
Other Name: ABT-414

Radiation: Radiation
Placebo Comparator: Placebo, Radiation and TMZ
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.
 Drug: Temozolomide
Oral Capsule

Radiation: Radiation
Drug: Placebo for ABT-414
IV Infusion (IV)
Experimental: Open-Label Sub-Study: Depatuxizumab Mafodotin, Radiation and TMZ
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.
 Drug: Temozolomide
Oral Capsule

Drug: Depatuxizumab mafodotin
Intravenous (IV) Infusion
Other Name: ABT-414

Radiation: Radiation


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: 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 :
  1. OS for the O6-methylguaninemethlytransferese (MGMT) Unmethylated Group [ Time Frame: 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


  2. OS for the MGMT Methylated Group [ Time Frame: 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.

  3. OS for the Epidermal Growth Factor Receptor (EGFR)vIII-Mutated Tumor Subgroup [ Time Frame: 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.

  4. Progression-Free Survival (PFS) [ Time Frame: 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.

  5. PFS for EGFRvIII-Mutated Tumor Subgroup [ Time Frame: 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.

  6. Deterioration Free Survival in M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) Symptom Severity Score [ Time Frame: 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.

  7. Deterioration Free Survival in MDASI-BT Symptom Interference Score [ Time Frame: 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.

  8. Deterioration Free Survival in Neurocognitive Functioning on the Hopkins Verbal Learning Test Revised (HVLT-R) Total Recall Score [ Time Frame: 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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02573324


Locations
Show Show 212 study locations
Sponsors and Collaborators
AbbVie
Radiation Therapy Oncology Group
Investigators
Layout table for investigator information
Study Director: ABBVIE INC. AbbVie
  Study Documents (Full-Text)

Documents provided by AbbVie:
Study Protocol  [PDF] May 26, 2019
Statistical Analysis Plan  [PDF] April 23, 2019

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02573324    
Other Study ID Numbers: M13-813
2015-001166-26 ( EudraCT Number )
First Posted: October 9, 2015    Key Record Dates
Results First Posted: May 11, 2023
Last Update Posted: May 11, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
URL: https://vivli.org/ourmember/abbvie/

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AbbVie:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
 Neoplasms, Nerve Tissue
Temozolomide
ABT-414
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs