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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03419403




Registration number
NCT03419403
Ethics application status
Date submitted
26/01/2018
Date registered
5/02/2018
Date last updated
3/04/2020

Titles & IDs
Public title
UNITE Study: Understanding New Interventions With GBM ThErapy
Scientific title
Phase 3b Study for Management of Ocular Side Effects in Subjects With EGFR-amplified Glioblastoma Receiving Depatuxizumab Mafodotin (ABT-414)
Secondary ID [1] 0 0
2017-003171-64
Secondary ID [2] 0 0
M16-534
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma Multiforme 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Steroid eye drop
Treatment: Drugs - Ophthalmic steroid ointment
Treatment: Other - Radiation
Treatment: Drugs - Temozolomide
Treatment: Drugs - depatuxizumab mafodotin
Other interventions - cold compress
Treatment: Drugs - Vasoconstrictor eye drop

Experimental: Arm B: Standard Steroids + Vasoconstrictor + Cold Compress - Arm B: Steroid eye drop plus vasoconstrictor eye drop and cold compress plus depatuxizumab mafodotin during both the chemoradiation therapy (RT and TMZ) and the adjuvant therapy [TMZ] periods of this study.

Experimental: Arm A: Standard Steroid (SS) - Arm A: Steroid Eye Drops plus depatuxizumab mafodotin during both the chemoradiation therapy (radiation [RT] and temozolomide [TMZ]) and the adjuvant therapy [TMZ] periods of this study.

Experimental: Arm C: Enhanced Steroids+Vasoconstrictor+Cold Compress (ES/VC) - Arm C: Steroid Eye Drop plus ophthalmic steroid ointment plus vasoconstrictor eye drop and cold compresses plus depatuxizumab mafodotin during both the chemoradiation therapy (RT and TMZ) and the adjuvant therapy [TMZ] periods of this study.


Treatment: Drugs: Steroid eye drop
solution, eye drop

Treatment: Drugs: Ophthalmic steroid ointment
ointment

Treatment: Other: Radiation
radiation

Treatment: Drugs: Temozolomide
oral

Treatment: Drugs: depatuxizumab mafodotin
infusion

Other interventions: cold compress
cold compress

Treatment: Drugs: Vasoconstrictor eye drop
solution, eye drop

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Participants who Require a Change in Ocular Side Effect (OSE) Management - Ocular Side Effect (OSE) management is defined as a participant with >= 3-line loss (+ 0.3 on LogMAR scale or equivalent) of best corrected visual acuity from baseline (with prescription at baseline for those using corrective lens), or >= Grade 3 OSE severity on the Corneal Epithelial Adverse Event [CEAE] scale.
Timepoint [1] 0 0
Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin
Secondary outcome [1] 0 0
Cumulative Dose of Depatuxizumab Mafodotin - Cumulative dose of depatuxizumab mafodotin administered (mg/kg).
Timepoint [1] 0 0
Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin
Secondary outcome [2] 0 0
Change from Baseline In Logarithm of the Minimum Angle of Resolution (LogMAR) Scale after Bandage Contact Lenses (BCL) Intervention - Change on LogMAR Scale from last assessment prior to BCL intervention to 2 weeks after BCL intervention. 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.
Timepoint [2] 0 0
Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin
Secondary outcome [3] 0 0
Time to OSE Symptom Resolution after Drug Discontinuation (reversibility) - Time from discontinuation of depatuxizumab mafodotin to OSE symptom resolution (reversibility).
Timepoint [3] 0 0
Up to approximately 3 years after initial dose of depatuxizumab mafodotin
Secondary outcome [4] 0 0
Time to BCL Intervention - Time to initiation of bandage contact lenses (BCL) intervention.
Timepoint [4] 0 0
Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin
Secondary outcome [5] 0 0
Participants that recover to <3-line decline from Baseline (<= +0.3 LogMAR) in visual acuity after BCL Intervention - Recovery is defined as return to <3-line decline from baseline (<= +0.3 LogMAR) in visual acuity after BCL intervention.
Timepoint [5] 0 0
Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin
Secondary outcome [6] 0 0
Corneal Epithelial Adverse Event (CEAE) Grade - 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).
Timepoint [6] 0 0
Up to approximately 3 years after initial dose of depatuxizumab mafodotin
Secondary outcome [7] 0 0
Time to Re-initiation of Depatuxizumab Mafodotin after Dose Interruption - Time from dose interruption until re-initiation or permanent discontinuation of depatuxizumab mafodotin.
Timepoint [7] 0 0
Up to approximately 3 years after initial dose of depatuxizumab mafodotin
Secondary outcome [8] 0 0
Participants with Depatuxizumab Mafodotin Dose Interruptions due to OSEs - Participants with dose interruptions of depatuxizumab mafodotin due to ocular side effects (OSEs).
Timepoint [8] 0 0
Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin
Secondary outcome [9] 0 0
Participants with Depatuxizumab Mafodotin Dose Reductions due to OSEs - Dose reductions of depatuxizumab mafodotin initiated due to OSEs.
Timepoint [9] 0 0
Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin
Secondary outcome [10] 0 0
Maximum Change from Baseline on LogMAR Scale - The Logarithm of the Minimum Angle of Resolution (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.
Timepoint [10] 0 0
Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participants with newly diagnosed GBM: has received prior chemotherapy or radiotherapy
for cancer of the head and neck region; has received prior treatment with Gliadel
wafers or any other intratumoral or intracavitary treatment.

- Participant has hypersensitivity to any component of TMZ 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Royal North Shore Hospital /ID# 169673 - Saint Leonards
Recruitment hospital [2] 0 0
Calvary Mater Newcastle /ID# 169672 - Waratah
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital /ID# 169674 - Herston
Recruitment hospital [4] 0 0
Austin Hospital /ID# 169671 - Heidelberg
Recruitment postcode(s) [1] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
Germany
State/province [7] 0 0
Baden-Wuerttemberg
Country [8] 0 0
Germany
State/province [8] 0 0
Sachsen
Country [9] 0 0
Germany
State/province [9] 0 0
Regensburg
Country [10] 0 0
Germany
State/province [10] 0 0
Tuebingen
Country [11] 0 0
Netherlands
State/province [11] 0 0
Amsterdam
Country [12] 0 0
Netherlands
State/province [12] 0 0
Utrecht
Country [13] 0 0
United Kingdom
State/province [13] 0 0
London, City Of
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Birmingham
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Cottingham
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Edinburgh

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will 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 are being treated with
depatuxizumab mafodotin (ABT-414). The study will include 2 phases during the treatment
period: chemoradiation therapy (radiation plus temozolomide [RT/TMZ]) and adjuvant therapy
(TMZ ). All participants will receive depatuxizumab mafodotin during both phases of the
treatment period plus 1 of 3 prophylactic ophthalmologic treatments (standard steroids [SS],
standard steroids with vasoconstrictors and cold compress [SS/VC], and enhanced steroids with
vasoconstrictors and cooling compress [ES/VC]).
Trial website
https://clinicaltrials.gov/show/NCT03419403
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications