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

AbbVie

Status and phase: Completed; Phase 3

Conditions: Glioblastoma; Gliosarcoma

Treatments: Radiation: Radiation; Drug: Placebo for ABT-414; Drug: Temozolomide; Drug: Depatuxizumab mafodotin

Study type: Interventional

Funder types: NETWORK; Industry

Identifiers

NCT02573324

M13-813

2015-001166-26 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 691 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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691 participants in 3 patient groups, including a placebo group

Depatuxizumab Mafodotin, Radiation and Temozolomide (TMZ)

Experimental group

Description:

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.

Treatment:

Radiation: Radiation

Drug: Depatuxizumab mafodotin

Drug: Temozolomide

Placebo, Radiation and TMZ

Placebo Comparator group

Description:

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.

Treatment:

Radiation: Radiation

Drug: Placebo for ABT-414

Drug: Temozolomide

Open-Label Sub-Study: Depatuxizumab Mafodotin, Radiation and TMZ

Experimental group

Description:

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.

Treatment:

Radiation: Radiation

Drug: Depatuxizumab mafodotin

Drug: Temozolomide