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

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ClinicalTrials.gov Identifier: NCT02573324
Recruitment Status : Recruiting
First Posted : October 9, 2015
Last Update Posted : June 21, 2018
Sponsor:
Collaborator:
Radiation Therapy Oncology Group
Information provided by (Responsible Party):
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.


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

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Detailed Description:
The main study for all countries except China is closed. The sub-study of ABT-414 (number of participants being sought=12) in participants with newly diagnosed EGFR-amplified GBM who have mild or moderate hepatic impairment is open to enrollment.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 640 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
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 : December 7, 2015
Estimated Primary Completion Date : March 18, 2020
Estimated Study Completion Date : February 13, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 & 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase.
Drug: Temozolomide
oral

Radiation: Radiation
Drug: Placebo for ABT-414
intravenous infusion

Experimental: ABT-414, radiation and TMZ
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.
Drug: Temozolomide
oral

Drug: ABT-414
intravenous infusion
Other Names:
  • Depatuxizumab
  • Mafodotin

Radiation: Radiation



Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Quarterly after treatment discontinuation for approximately 4 years ]
    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) methylated subgroup [ Time Frame: Quarterly after treatment discontinuation for approximately 4 years ]
    Time to OS is defined as the number of days from the date of randomization to the date of death due to any cause.

  2. Number of days to deterioration in symptom severity score M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) [ Time Frame: At Screening, every 8 weeks until disease progression, and post-progression, for an average of up to 2 years. ]
    Number of days from baseline to 1 point or greater increase in MDASI-BT symptom severity score.

  3. OS for the EGFRvIII-mutated tumor subgroup [ Time Frame: Quarterly after treatment discontinuation for approximately 4 years ]
    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. Number of days to deterioration in neurocognitive functioning on the Hopkins Verbal Learning Test Revised (HVLT-R) [ Time Frame: At Screening, every 8 weeks until disease progression, and post-progression, for an average of up to 2 years. ]
    Number of days from baseline to decline using the reliable change index (RCI) criterion based on raw scores.

  5. Progression Free Survival (PFS) [ Time Frame: At Baseline, then every 8 weeks, at follow up visits and at the final study drug visit, for an average of up to 2 years. ]
    Time to PFS is 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 (as determined by the Investigator) or to the date of death, if disease progression does not occur.

  6. Number of days to deterioration in symptom interference score (MDASI-BT) [ Time Frame: At Screening, every 8 weeks until disease progression, at post-progression, for an average of up to 2 years. ]
    Number of days from baseline to 1 point or greater increase in MDASI-BT symptom interference score.

  7. PFS for EGFRvIII-mutated tumor subgroup [ Time Frame: At Baseline, then every 8 weeks, at follow up visits and at the final study drug visit, for an average of up to 2 years. ]
    Time to PFS is 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 (as determined by the Investigator) or to the date of death, if disease progression does not occur.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Must have a clinical diagnosis of Glioblastoma (GBM)
  2. Must have a confirmed Epidermal growth factor receptor amplification in tumor tissue
  3. Must have a Karnofsky Performance Status (KPS) >= 70 at assessment <= 14 days prior to randomization (N/A to the sub-study).
  4. Must have recovered from effects of surgery, postoperative infection and other complications of surgery
  5. Must have adequate bone marrow, renal, and hepatic function (For the sub-study, the subject must have adequate bone marrow and renal function and have mild-to-moderate hepatic impairment)

Exclusion Criteria:

  1. Multifocal, recurrent or metastatic Glioblastoma (GBM) or gliomatosis cerebri (For the sub-study, the subject can have multifocal GBM and gliomatosis cerebri but can't have recurrent or metastatic GBM)
  2. Prior chemo therapy or radiosensitizer for head and neck cancer
  3. Prior radiotherapy to the head or neck in overlap of radiation fields
  4. Prior therapy for glioblastoma or other invasive malignancy
  5. Prior, concomitant or planned treatment with Novo-TTF, EGFR-targeted therapy, bevacizumab, Gliadel wafers or other intratumoral or intracavity anti-neoplastic therapy

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


Contacts
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

  Show 215 Study Locations
Sponsors and Collaborators
AbbVie
Radiation Therapy Oncology Group
Investigators
Study Director: AbbVie Inc. AbbVie

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02573324     History of Changes
Other Study ID Numbers: M13-813
2015-001166-26 ( EudraCT Number )
First Posted: October 9, 2015    Key Record Dates
Last Update Posted: June 21, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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:
Astrocytoma
Glioblastoma
Gliosarcoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Mitogens
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators