UNITE Study: Understanding New Interventions With GBM ThErapy

NCT03419403 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: M16-5342017-003171-64
• Study Type: interventional
• Target: 40
• Locations: 5 countries
• Sites: 22

Brief Summary

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).

Conditions

Glioblastoma Multiforme

Keywords

Glioblastoma Multiforme (GBM); Cancer; Chemoradiation therapy; Epidermal growth factor receptor-amplified glioblastoma; Radiation; Temozolomide

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Required a Change in Ocular Side Effect (OSE) Management

  Inadequate control of ocular side effects (OSE) was defined as either a ≥ 3-line decline from baseline (≥ +0.3 on LogMAR scale) in visual acuity (with baseline correction determined at the screening ophthalmology visit)) or ≥ Grade 3 OSE severity on the Corneal Epithelial Adverse Event (CEAE) scale.

  Within 8 weeks after the initial dose of depatuxizumab mafodotin

Secondary Outcomes (12)

• Maximum Change From Baseline on the Logarithm of the Minimum Angle of Resolution (LogMAR) Scale

  Within 8 weeks after the initial dose of depatuxizumab mafodotin

• Time to Bandage Contact Lens (BCL) Intervention

  Up to 9 months after the first dose of depatuxizumab mafodotin

• Number of Participants With Depatuxizumab Mafodotin Dose Modifications Due to Ocular Side Effects (OSE)

  From the first dose of study drug until 49 days after last depatuxizumab mafodotin administration, up to 47 weeks

• Cumulative Dose of Depatuxizumab Mafodotin Received During Chemoradiation and During Adjuvant Treatment

  Up to 9 months

• Treatment-Emergent Corneal Epithelial Adverse Event (CEAE) Grade at Each Visit

  Up to 47 weeks

Study Arms (3)

Standard Steroids

EXPERIMENTAL

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

Drug: Steroid eye drops; Drug: Depatuxizumab mafodotin; Drug: Temozolomide; Radiation: Radiation

Standard Steroids + Vasoconstrictor + Cold Compress

EXPERIMENTAL

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).

Drug: Steroid eye drops; Drug: Vasoconstrictor eye drops; Other: Cold compress; Drug: Depatuxizumab mafodotin; Drug: Temozolomide; Radiation: Radiation

Enhanced Steroids + Vasoconstrictor + Cold Compress

EXPERIMENTAL

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).

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

Interventions

Steroid eye drops DRUG

Solution, eye drop

Enhanced Steroids + Vasoconstrictor + Cold Compress; Standard Steroids; Standard Steroids + Vasoconstrictor + Cold Compress

Vasoconstrictor eye drops DRUG

Solution, eye drop

Enhanced Steroids + Vasoconstrictor + Cold Compress; Standard Steroids + Vasoconstrictor + Cold Compress

Cold compress OTHER

Cold compress

Enhanced Steroids + Vasoconstrictor + Cold Compress; Standard Steroids + Vasoconstrictor + Cold Compress

Ophthalmic steroid ointment DRUG

Ointment

Enhanced Steroids + Vasoconstrictor + Cold Compress

Depatuxizumab mafodotin DRUG

During the Chemoradiation Phase, participants were to receive depatuxizumab mafodotin at 2.0 mg/kg IV infusion over 30 - 40 minutes once every 2 weeks (Day 1 of Weeks 1, 3, and 5 of the 6-week regimen). During the Adjuvant Therapy Phase, participants were to receive depatuxizumab mafodotin at 1.25 mg/kg on Day 1 (± 2 days) and Day 15 (± 2 days) of each 28-day cycle as a 30 - 40 minute infusion for 12 cycles.

Also known as: ABT-414

Enhanced Steroids + Vasoconstrictor + Cold Compress; Standard Steroids; Standard Steroids + Vasoconstrictor + Cold Compress

Temozolomide DRUG

Temozolomide was to be administered according to the local standard of care. Duration of treatment was to be 6 - 12 cycles in the adjuvant phase and at the discretion of the investigator as supported by local standard of care.

Enhanced Steroids + Vasoconstrictor + Cold Compress; Standard Steroids; Standard Steroids + Vasoconstrictor + Cold Compress

Radiation RADIATION

Radiation therapy treatment planning and administration was to be performed as per local institutional guidelines.

Enhanced Steroids + Vasoconstrictor + Cold Compress; Standard Steroids; Standard Steroids + Vasoconstrictor + Cold Compress

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• AbbVie: lead

Study Sites (22)

Usc /Id# 164235

Los Angeles, California, 90033, United States

Location

Moffitt Cancer Center /ID# 164234

Tampa, Florida, 33612-9416, United States

Location

Rush University Medical Center /ID# 171003

Chicago, Illinois, 60612, United States

Location

Northshore University Health System-Evanston /ID# 164221

Evanston, Illinois, 60201, United States

Location

CDH-Delnor Health System /ID# 169909

Warrenville, Illinois, 60555, United States

Location

Columbia University Medical Center /ID# 164220

New York, New York, 10032-3729, United States

Location

Levine Cancer Ins, Carolina Me /ID# 171271

Charlotte, North Carolina, 28204, United States

Location

UT Health Science Ctr-Houston /ID# 164223

Houston, Texas, 77030, United States

Location

Baylor Scott & White Medical Center- Temple /ID# 170792

Temple, Texas, 76508-0001, United States

Location

Royal North Shore Hospital /ID# 169673

Saint Leonards, New South Wales, 2065, Australia

Location

Calvary Mater Newcastle /ID# 169672

Waratah, New South Wales, 2298, Australia

Location

Royal Brisbane and Women's Hospital /ID# 169674

Herston, Queensland, 4029, Australia

Location

Austin Hospital /ID# 169671

Heidelberg, Victoria, 3084, Australia

Location

Universitaetsklinik Heidelberg /ID# 169970

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitaetsklinikum Leipzig /ID# 169969

Leipzig, Saxony, 04103, Germany

Location

Klinikum Univ. Regensburg /ID# 169963

Regensburg, 93042, Germany

Location

Universitatsklinikum Tubingen /ID# 169965

Tübingen, 72076, Germany

Location

Vrije Universiteit Medisch Centrum /ID# 170152

Amsterdam, 1081 HV, Netherlands

Location

Universitair Medisch Centrum Utrecht /ID# 170149

Utrecht, 3584 CX, Netherlands

Location

Guy's and St Thomas' NHS Found /ID# 207752

London, London, City of, SE1 9RT, United Kingdom

Location

Queen Elizabeth Hospital - BIRMINGHAM /ID# 200657

Birmingham, B15 2TH, United Kingdom

Location

Castle Hill Hospital /ID# 200662

Cottingham, HU16 5JQ, United Kingdom

Location

MeSH Terms

Conditions

Glioblastoma; Neoplasms

Interventions

depatuxizumab mafodotin; ABT-414; Temozolomide; Radiation

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Physical Phenomena

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: January 26, 2018
• First Posted: February 5, 2018
• Study Start: July 30, 2018
• Primary Completion: September 5, 2019
• Study Completion: March 3, 2020
• Last Updated: April 14, 2021
• Results First Posted: April 14, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• 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 (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.

Locations

US (9); NL (2); AU (4); DE (4); GB (3)