Clinical trial NCT03419403: UNITE Study: Understanding New Interventions With GBM ThErapy
Official title: Phase 3b Study for Management of Ocular Side Effects in Subjects With EGFR-amplified Glioblastoma Receiving Depatuxizumab Mafodotin (ABT-414)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Glioblastoma Multiforme
Keywords: Glioblastoma Multiforme (GBM)
Cancer
Chemoradiation therapy
Epidermal growth factor receptor-amplified glioblastoma
Radiation
Temozolomide
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2018-02-05
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Percentage of Participants Who Required a Change in Ocular Side Effect (OSE) Management
timeFrame: Within 8 weeks after the initial dose of depatuxizumab mafodotin
Secondary outcomes:
measure: Maximum Change From Baseline on the Logarithm of the Minimum Angle of Resolution (LogMAR) Scale
timeFrame: Within 8 weeks after the initial dose of depatuxizumab mafodotin
measure: Time to Bandage Contact Lens (BCL) Intervention
timeFrame: Up to 9 months after the first dose of depatuxizumab mafodotin
measure: Number of Participants With Depatuxizumab Mafodotin Dose Modifications Due to Ocular Side Effects (OSE)
timeFrame: From the first dose of study drug until 49 days after last depatuxizumab mafodotin administration, up to 47 weeks
measure: Cumulative Dose of Depatuxizumab Mafodotin Received During Chemoradiation and During Adjuvant Treatment
timeFrame: Up to 9 months
measure: Treatment-Emergent Corneal Epithelial Adverse Event (CEAE) Grade at Each Visit
timeFrame: Up to 47 weeks
measure: Change From Baseline In Logarithm of the Minimum Angle of Resolution (LogMAR) Scale After Bandage Contact Lens (BCL) Intervention
timeFrame: From the last assessment prior to BCL intervention to 2 weeks after BCL intervention
measure: Percentage of Participants That Recovered to <3-line Decline From Baseline (≤ +0.3 LogMAR) in Visual Acuity After Bandage Contact Lens (BCL) Intervention
timeFrame: From the last assessment prior to BCL intervention to the end of BCL intervention
measure: Number of Participants With Depatuxizumab Mafodotin Dose Modifications to Ocular Side Effects After Bandage Contact Lens (BCL) Intervention
timeFrame: From the last assessment prior to BCL intervention to the end of BCL intervention, up to 38 weeks
measure: Time to Restart Depatuxizumab Mafodotin if Interrupted Due to Ocular Side Effects After Bandage Contact Lens (BCL) Intervention
timeFrame: From the last assessment prior to BCL intervention to the end of BCL intervention
measure: Treatment Emergent Corneal Epithelial Adverse Event (CEAE) Grade at Each Visit After Bandage Contact Lens (BCL) Intervention
timeFrame: From the last assessment prior to BCL intervention to the end of BCL intervention, up to 38 weeks
measure: Time to Ocular Side Effect (OSE) Symptom Resolution After Drug Discontinuation (Reversibility)
timeFrame: From the first dose of study drug until 49 days after last depatuxizumab mafodotin administration, up to 47 weeks
measure: Time to Re-initiation of Depatuxizumab Mafodotin After Dose Interruption
timeFrame: Up to 9 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Usc /Id# 164235
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center /ID# 164234
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center /ID# 171003
state: Illinois
city: Evanston
country: United States
facility: Northshore University Health System-Evanston /ID# 164221
state: Illinois
city: Warrenville
country: United States
facility: CDH-Delnor Health System /ID# 169909
state: Illinois
city: New York
country: United States
facility: Columbia University Medical Center /ID# 164220
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Ins, Carolina Me /ID# 171271
state: North Carolina
city: Houston
country: United States
facility: UT Health Science Ctr-Houston /ID# 164223
state: Texas
city: Temple
country: United States
facility: Baylor Scott & White Medical Center- Temple /ID# 170792
state: Texas
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital /ID# 169673
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle /ID# 169672
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital /ID# 169674
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Hospital /ID# 169671
state: Victoria
city: Heidelberg
country: Germany
facility: Universitaetsklinik Heidelberg /ID# 169970
state: Baden-Wuerttemberg
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig /ID# 169969
state: Sachsen
city: Regensburg
country: Germany
facility: Klinikum Univ. Regensburg /ID# 169963
city: Tuebingen
country: Germany
facility: Universitatsklinikum Tubingen /ID# 169965
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum /ID# 170152
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht /ID# 170149
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Found /ID# 207752
state: London, City Of
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital - BIRMINGHAM /ID# 200657
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital /ID# 200662
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References: