UNITE Study: Understanding New Interventions With GBM ThErapy

Phase 3b Study for Management of Ocular Side Effects in Subjects With EGFR-amplified Glioblastoma Receiving Depatuxizumab Mafodotin (ABT-414)

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).

Study Overview

• Status: Terminated
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Drug: Steroid eye drops; Drug: Depatuxizumab mafodotin; Drug: Temozolomide; Radiation: Radiation; Drug: Vasoconstrictor eye drops; Other: Cold compress; Drug: Ophthalmic steroid ointment

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Saint Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital /ID# 169673
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle /ID# 169672
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital /ID# 169674
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital /ID# 169671
• Germany
  • Regensburg, Germany, 93042
    • Klinikum Univ. Regensburg /ID# 169963
  • Tuebingen, Germany, 72076
    • Universitatsklinikum Tubingen /ID# 169965
  • Baden-Wuerttemberg
    • Heidelberg, Baden-Wuerttemberg, Germany, 69120
      • Universitaetsklinik Heidelberg /ID# 169970
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • Universitaetsklinikum Leipzig /ID# 169969
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Vrije Universiteit Medisch Centrum /ID# 170152
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht /ID# 170149
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital - BIRMINGHAM /ID# 200657
  • Cottingham, United Kingdom, HU16 5JQ
    • Castle Hill Hospital /ID# 200662
  • London, City Of
    • London, London, City Of, United Kingdom, SE1 9RT
      • Guy's and St Thomas' NHS Found /ID# 207752
• United States
  • California
    • Los Angeles, California, United States, 90033
      • Usc /Id# 164235
  • Florida
    • Tampa, Florida, United States, 33612-9416
      • Moffitt Cancer Center /ID# 164234
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center /ID# 171003
    • Evanston, Illinois, United States, 60201
      • Northshore University Health System-Evanston /ID# 164221
    • Warrenville, Illinois, United States, 60555
      • CDH-Delnor Health System /ID# 169909
  • New York
    • New York, New York, United States, 10032-3729
      • Columbia University Medical Center /ID# 164220
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Ins, Carolina Me /ID# 171271
  • Texas
    • Houston, Texas, United States, 77030
      • UT Health Science Ctr-Houston /ID# 164223
    • Temple, Texas, United States, 76508-0001
      • Baylor Scott & White Medical Center- Temple /ID# 170792

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard Steroids; 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; Solution, eye drop; Drug: Depatuxizumab mafodotin; 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.; Other Names: ABT-414; Drug: Temozolomide; 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.; Radiation: Radiation; Radiation therapy treatment planning and administration was to be performed as per local institutional guidelines.
Experimental: Standard Steroids + Vasoconstrictor + Cold Compress; 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; Solution, eye drop; Drug: Depatuxizumab mafodotin; 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.; Other Names: ABT-414; Drug: Temozolomide; 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.; Radiation: Radiation; Radiation therapy treatment planning and administration was to be performed as per local institutional guidelines.; Drug: Vasoconstrictor eye drops; Solution, eye drop; Other: Cold compress; Cold compress
Experimental: Enhanced Steroids + Vasoconstrictor + Cold Compress; 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; Solution, eye drop; Drug: Depatuxizumab mafodotin; 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.; Other Names: ABT-414; Drug: Temozolomide; 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.; Radiation: Radiation; Radiation therapy treatment planning and administration was to be performed as per local institutional guidelines.; Drug: Vasoconstrictor eye drops; Solution, eye drop; Other: Cold compress; Cold compress; Drug: Ophthalmic steroid ointment; Ointment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Change From Baseline on the Logarithm of the Minimum Angle of Resolution (LogMAR) Scale	The LogMAR scale measures visual acuity on a continuous scale, with a LogMAR value of 0 equivalent to 20/20 visual acuity. Normal vision is considered to be from -0.2 - 0.1; higher values indicate visual impairment. The baseline observation is defined as the last non-missing measurement collected prior to the first dose of depatuxizumab mafodotin.	Within 8 weeks after the initial dose of depatuxizumab mafodotin
Time to Bandage Contact Lens (BCL) Intervention	The time to initiation of bandage contact lenses for those participants who required intervention due to inadequate control of ocular side effects (OSE) was calculated.	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)	Dose modifications included depatuxizumab mafodotin withdrawal, interruption, and reductions in dose initiated due to OSEs.	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	The cumulative dose of depatuxizumab mafodotin administered was tabulated.	Up to 9 months
Treatment-Emergent Corneal Epithelial Adverse Event (CEAE) Grade at Each Visit	The corneal epithelial adverse event (CEAE) rating scale is designed to record symptoms associated with corneal epitheliopathy caused by antibody-drug conjugates and to grade the severity of findings. The overall CEAE grade is measured on a scale of 0 to 5, with higher values being more severe, reflecting the impact of corneal abnormalities on visual activities of daily living (ADLs). Additional detailed information is collected for specific domains that are commonly affected, with the following ranges (each in order of increasing severity): ocular discomfort (0 - 4), photophobia (0 - 3), and reading (1 - 3).	Up to 47 weeks
Change From Baseline In Logarithm of the Minimum Angle of Resolution (LogMAR) Scale After Bandage Contact Lens (BCL) Intervention	The change on the LogMAR Scale from last assessment prior to BCL intervention to 2 weeks after BCL intervention was calculated. The LogMAR scale measures visual acuity on a continuous scale, with a LogMAR value of 0 equivalent to 20/20 visual acuity. Normal vision is considered to be from -0.2 - 0.1; higher values indicate visual impairment.	From the last assessment prior to BCL intervention to 2 weeks after BCL intervention
Percentage of Participants That Recovered to <3-line Decline From Baseline (≤ +0.3 LogMAR) in Visual Acuity After Bandage Contact Lens (BCL) Intervention	Recovery was defined as return to <3-line decline from baseline (≤ +0.3 LogMAR) in visual acuity after BCL intervention.	From the last assessment prior to BCL intervention to the end of BCL intervention
Number of Participants With Depatuxizumab Mafodotin Dose Modifications to Ocular Side Effects After Bandage Contact Lens (BCL) Intervention	Dose modifications included depatuxizumab mafodotin withdrawal, interruption, and reductions in dose initiated due to OSEs after BCL intervention.	From the last assessment prior to BCL intervention to the end of BCL intervention, up to 38 weeks
Time to Restart Depatuxizumab Mafodotin if Interrupted Due to Ocular Side Effects After Bandage Contact Lens (BCL) Intervention	The time to restart depatuxizumab mafodotin treatment if it was interrupted due to ocular side effects after BCL Intervention was tabulated.	From the last assessment prior to BCL intervention to the end of BCL intervention
Treatment Emergent Corneal Epithelial Adverse Event (CEAE) Grade at Each Visit After Bandage Contact Lens (BCL) Intervention	The corneal epithelial adverse event (CEAE) rating scale is designed to record symptoms associated with corneal epitheliopathy caused by antibody-drug conjugates and to grade the severity of findings. The overall CEAE grade is measured on a scale of 0 to 5, with higher values being more severe, reflecting the impact of corneal abnormalities on visual activities of daily living (ADLs). Additional detailed information is collected for specific domains that are commonly affected, with the following ranges (each in order of increasing severity): ocular discomfort (0 - 4), photophobia (0 - 3), and reading (1 - 3).	From the last assessment prior to BCL intervention to the end of BCL intervention, up to 38 weeks
Time to Ocular Side Effect (OSE) Symptom Resolution After Drug Discontinuation (Reversibility)	The time from discontinuation of depatuxizumab mafodotin to OSE symptom resolution (reversibility) was to be recorded.	From the first dose of study drug until 49 days after last depatuxizumab mafodotin administration, up to 47 weeks
Time to Re-initiation of Depatuxizumab Mafodotin After Dose Interruption	The time from dose interruption until re-initiation or permanent discontinuation of depatuxizumab mafodotin was to be recorded.	Up to 9 months

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2018
• Primary Completion (Actual): September 5, 2019
• Study Completion (Actual): March 3, 2020

Study Registration Dates

• First Submitted: January 26, 2018
• First Submitted That Met QC Criteria: January 26, 2018
• First Posted (Actual): February 5, 2018

Study Record Updates

• Last Update Posted (Actual): April 14, 2021
• Last Update Submitted That Met QC Criteria: March 19, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Cancer; Temozolomide; Radiation; Chemoradiation therapy; Glioblastoma Multiforme (GBM); Epidermal growth factor receptor-amplified glioblastoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Pharmaceutical Solutions; Temozolomide; Ophthalmic Solutions; Vasoconstrictor Agents
• Other Study ID Numbers: M16-534; 2017-003171-64 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• 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