UNITE Study: Understanding New Interventions With GBM ThErapy

AbbVie

Status and phase: Terminated; Phase 3

Conditions: Glioblastoma Multiforme

Treatments: Drug: Temozolomide; Drug: Vasoconstrictor eye drops; Drug: Depatuxizumab mafodotin; Drug: Steroid eye drops; Drug: Ophthalmic steroid ointment; Other: Cold compress; Radiation: Radiation

Study type: Interventional

Funder types: Industry

Identifiers

NCT03419403

M16-534

2017-003171-64 (EudraCT Number)

Details and patient eligibility

About

The objective of this study was to evaluate the effect of several ophthalmologic prophylactic treatment strategies for the management of ocular side effects (OSEs) in participants with epidermal growth factor receptor (EGFR)-amplified glioblastoma (GBM) who were being treated with depatuxizumab mafodotin (ABT-414).

Full description

This Phase 3b open-label, randomized, exploratory study included 2 phases during the treatment period: chemoradiation therapy (radiation plus temozolomide [RT/TMZ]) and adjuvant therapy (TMZ). All participants received depatuxizumab mafodotin during both phases of the treatment period plus 1 of 3 prophylactic ophthalmologic treatments (standard steroids; standard steroids with vasoconstrictors and cold compress; and enhanced steroids with vasoconstrictors and cold compress. The study comprised a screening period of up to 7 weeks after surgery, a 6-week concomitant Chemoradiation Phase, an Adjuvant Phase beginning approximately 4 weeks after completion of chemoradiation, and a Follow-Up Phase.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Newly diagnosed glioblastoma (GBM) histologically proven, World Health Organization (WHO) grade IV GBM or WHO grade IV gliosarcoma
• Tumors must demonstrate epidermal growth factor receptor (EGFR) amplification
• Tumors must be supratentorial in location
• Participant must have recovered from the effects of surgery, postoperative infection, and other complications; has no significant post-operative hemorrhage
• Participant has a Karnofsky performance status (KPS) of 70 or higher
• Participant has adequate bone marrow, renal, and hepatic function
• Electrocardiogram without evidence of acute cardiac ischemia ≤ 21 days prior to randomization
• Participant has a life expectancy of ≥ 3 months

Exclusion criteria

• Participant has received prior chemotherapy or radiotherapy for cancer of the head and neck region
• Participant has received prior treatment with Gliadel wafers or any other intratumoral or intracavitary treatment
• Participant has hypersensitivity to any component of temozolomide or dacarbazine
• Participant has received anti-cancer therapy (including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic, or any investigational therapy) within 5 years of Study Day 1
• Participant has clinically significant uncontrolled condition(s) as described in the protocol
• Participant has any medical condition which in the opinion of the investigator places the participant at an unacceptably high risk for toxicities
• Participant has had another active malignancy within the past 3 years except for any cancer considered cured or non-melanoma carcinoma of the skin
• Participant has a history of herpetic keratitis
• Participant is not suitable for receiving ocular steroids with conditions as described in the protocol
• Participant has had laser-assisted in situ keratomileusis (LASIK) procedure within the last 1 year or cataract surgery within the last 3 months
• Participant has a visual condition that compromises the ability to accurately measure visual acuity or assess visual activities of daily living (vADLs)
• Participant has hepatitis B virus or hepatitis C virus infection
• Participant not receiving treatment with highly active antiretroviral therapy (HAART) when positive for human immunodeficiency virus (HIV)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 3 patient groups

Standard Steroids

Experimental group

Description:

Steroid eye drops: 1 drop each eye, 3 times/day, starting 2 days prior to depatuxizumab mafodotin infusion and continuing until 4 days after infusion, for a total of 7 days

Treatment:

Radiation: Radiation

Drug: Temozolomide

Drug: Steroid eye drops

Drug: Depatuxizumab mafodotin

Standard Steroids + Vasoconstrictor + Cold Compress

Experimental group

Description:

Steroid eye drops: 1 drop each eye, 3 times/day, starting 2 days prior to depatuxizumab mafodotin infusion and continuing until 4 days after infusion, for a total of 7 days; Vasoconstrictor Eye Drops: 1 drop each eye 4 - 6 times on day of infusion in total (5 - 10 minutes before infusion; at end of infusion; and 2 - 4 times during the remainder of the infusion day). Continuing 4 - 6 times/day on Day 1 and Day 2 after each depatuxizumab mafodotin infusion; Cold Compress: Starting 5 minutes prior to start of infusion and continuing for 30 minutes past end of infusion, and then use at least 2 hours total/day on Days 1 - 3 with each depatuxizumab mafodotin infusion. The cold compress was to be applied in increments no longer than 30 min (could be shorter if the participant was uncomfortable).

Treatment:

Radiation: Radiation

Drug: Temozolomide

Drug: Steroid eye drops

Drug: Vasoconstrictor eye drops

Drug: Depatuxizumab mafodotin

Other: Cold compress

Enhanced Steroids + Vasoconstrictor + Cold Compress

Experimental group

Description:

Enhanced steroid eye drops: 1 drop each eye, 6 times/day, starting 2 days prior to depatuxizumab mafodotin infusion and continuing until 4 days after infusion, for a total of 7 days; Ophthalmic Steroid Ointment; applied to each eye once daily before sleep, starting 2 days prior to depatuxizumab mafodotin infusion and continuing until 4 days after infusion, for a total of 7 days; Vasoconstrictor Eye Drops: 1 drop each eye 4 - 6 times on day of infusion in total (5 - 10 minutes before infusion; at end of infusion; and 2 - 4 times during the remainder of the infusion day). Continuing 4 - 6 times/day on Day 1 and Day 2 after each depatuxizumab mafodotin infusion; Cold Compress: Starting 5 minutes prior to start of infusion and continuing for 30 minutes past end of infusion, and then use at least 2 hours total/day on Days 1 - 3 with each depatuxizumab mafodotin infusion. Cold compress was to be applied in increments no longer than 30 min (could be shorter if the patient is uncomfortable).

Treatment:

Radiation: Radiation

Drug: Temozolomide

Drug: Steroid eye drops

Drug: Ophthalmic steroid ointment

Drug: Vasoconstrictor eye drops

Drug: Depatuxizumab mafodotin

Other: Cold compress