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NCT Number: NCT02573324

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

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.

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Key information

Conditions

Glioblastoma Astrocytoma Brain Diseases Brain Neoplasms Central Nervous System Diseases Central Nervous System Neoplasms Glioma Gliosarcoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Nervous System Diseases Nervous System Neoplasms Neuroectodermal Tumors

Age range

18 year–99 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Sanatorio Parque /ID# 142825, Rosario, Santa Fe Province, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Temozolomide

Drug

Oral Capsule

Depatuxizumab mafodotin

Drug

Intravenous (IV) Infusion

Other names: ABT-414

Radiation

Radiation

Placebo for ABT-414

Drug

IV Infusion (IV)

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Collaborators

  • Radiation Therapy Oncology Group

Registry information

Official study 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)

Acronym: Intellance1

Important dates

Study start
2015
Primary completion
2022
Study completion
2022
First posted
Oct 9, 2015
Registry last updated
May 11, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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