UNITE Study: Understanding New Interventions With GBM ThErapy

Glioblastoma Multiforme Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03419403
• Other study ID #: M16-534
• Secondary ID: 2017-003171-64
• Status: Terminated
• Phase: Phase 3
• Start date: July 30, 2018
• Est. completion date: March 3, 2020

Study information

• Verified date: March 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: March 3, 2020
• Est. primary completion date: September 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Drug:
• Steroid eye drops
Solution, eye drop
• Vasoconstrictor eye drops
Solution, eye drop

Other:
• Cold compress
Cold compress

Drug:
• Ophthalmic steroid ointment
Ointment
• 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.
• 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.

Locations

Country	Name	City	State
Australia	Austin Hospital /ID# 169671	Heidelberg	Victoria
Australia	Royal Brisbane and Women's Hospital /ID# 169674	Herston	Queensland
Australia	Royal North Shore Hospital /ID# 169673	Saint Leonards	New South Wales
Australia	Calvary Mater Newcastle /ID# 169672	Waratah	New South Wales
Germany	Universitaetsklinik Heidelberg /ID# 169970	Heidelberg	Baden-Wuerttemberg
Germany	Universitaetsklinikum Leipzig /ID# 169969	Leipzig	Sachsen
Germany	Klinikum Univ. Regensburg /ID# 169963	Regensburg
Germany	Universitatsklinikum Tubingen /ID# 169965	Tuebingen
Netherlands	Vrije Universiteit Medisch Centrum /ID# 170152	Amsterdam
Netherlands	Universitair Medisch Centrum Utrecht /ID# 170149	Utrecht
United Kingdom	Queen Elizabeth Hospital - BIRMINGHAM /ID# 200657	Birmingham
United Kingdom	Castle Hill Hospital /ID# 200662	Cottingham
United Kingdom	Guy's and St Thomas' NHS Found /ID# 207752	London	London, City Of
United States	Levine Cancer Ins, Carolina Me /ID# 171271	Charlotte	North Carolina
United States	Rush University Medical Center /ID# 171003	Chicago	Illinois
United States	Northshore University Health System-Evanston /ID# 164221	Evanston	Illinois
United States	UT Health Science Ctr-Houston /ID# 164223	Houston	Texas
United States	Usc /Id# 164235	Los Angeles	California
United States	Columbia University Medical Center /ID# 164220	New York	New York
United States	Moffitt Cancer Center /ID# 164234	Tampa	Florida
United States	Baylor Scott & White Medical Center- Temple /ID# 170792	Temple	Texas
United States	CDH-Delnor Health System /ID# 169909	Warrenville	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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