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UNITE Study: Understanding New Interventions With GBM ThErapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03419403
Recruitment Status : Terminated (The study was terminated because clinical development of depatuxizumab mafodotin in glioblastoma was stopped due to lack of survival benefit.)
First Posted : February 5, 2018
Results First Posted : April 14, 2021
Last Update Posted : April 14, 2021
Sponsor:
Information provided by (Responsible Party):
AbbVie

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).

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Drug: Steroid eye drops Drug: Vasoconstrictor eye drops Other: Cold compress Drug: Ophthalmic steroid ointment Drug: Depatuxizumab mafodotin Drug: Temozolomide Radiation: Radiation Phase 3

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 3b Study for Management of Ocular Side Effects in Subjects With EGFR-amplified Glioblastoma Receiving Depatuxizumab Mafodotin (ABT-414)
Actual Study Start Date : July 30, 2018
Actual Primary Completion Date : September 5, 2019
Actual Study Completion Date : March 3, 2020

Resource links provided by the National Library of Medicine


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 Name: 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: Vasoconstrictor eye drops
Solution, eye drop

Other: Cold compress
Cold compress

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 Name: 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: 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: Vasoconstrictor eye drops
Solution, eye drop

Other: Cold compress
Cold compress

Drug: Ophthalmic steroid ointment
Ointment

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 Name: 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.




Primary Outcome Measures :
  1. Percentage of Participants Who Required a Change in Ocular Side Effect (OSE) Management [ Time Frame: Within 8 weeks after the initial dose of depatuxizumab mafodotin ]
    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.


Secondary Outcome Measures :
  1. Maximum Change From Baseline on the Logarithm of the Minimum Angle of Resolution (LogMAR) Scale [ Time Frame: Within 8 weeks after the initial dose of depatuxizumab mafodotin ]
    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.

  2. Time to Bandage Contact Lens (BCL) Intervention [ Time Frame: Up to 9 months after the first dose of depatuxizumab mafodotin ]
    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.

  3. Number of Participants With Depatuxizumab Mafodotin Dose Modifications Due to Ocular Side Effects (OSE) [ Time Frame: From the first dose of study drug until 49 days after last depatuxizumab mafodotin administration, up to 47 weeks ]
    Dose modifications included depatuxizumab mafodotin withdrawal, interruption, and reductions in dose initiated due to OSEs.

  4. Cumulative Dose of Depatuxizumab Mafodotin Received During Chemoradiation and During Adjuvant Treatment [ Time Frame: Up to 9 months ]
    The cumulative dose of depatuxizumab mafodotin administered was tabulated.

  5. Treatment-Emergent Corneal Epithelial Adverse Event (CEAE) Grade at Each Visit [ Time Frame: Up to 47 weeks ]
    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).

  6. Change From Baseline In Logarithm of the Minimum Angle of Resolution (LogMAR) Scale After Bandage Contact Lens (BCL) Intervention [ Time Frame: From the last assessment prior to BCL intervention to 2 weeks after 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.

  7. Percentage of Participants That Recovered to <3-line Decline From Baseline (≤ +0.3 LogMAR) in Visual Acuity After Bandage Contact Lens (BCL) Intervention [ Time Frame: From the last assessment prior to BCL intervention to the end of BCL intervention ]
    Recovery was defined as return to <3-line decline from baseline (≤ +0.3 LogMAR) in visual acuity after BCL intervention.

  8. Number of Participants With Depatuxizumab Mafodotin Dose Modifications to Ocular Side Effects After Bandage Contact Lens (BCL) Intervention [ Time Frame: From the last assessment prior to BCL intervention to the end of BCL intervention, up to 38 weeks ]
    Dose modifications included depatuxizumab mafodotin withdrawal, interruption, and reductions in dose initiated due to OSEs after BCL intervention.

  9. Time to Restart Depatuxizumab Mafodotin if Interrupted Due to Ocular Side Effects After Bandage Contact Lens (BCL) Intervention [ Time Frame: From the last assessment prior to BCL intervention to the end of BCL intervention ]
    The time to restart depatuxizumab mafodotin treatment if it was interrupted due to ocular side effects after BCL Intervention was tabulated.

  10. Treatment Emergent Corneal Epithelial Adverse Event (CEAE) Grade at Each Visit After Bandage Contact Lens (BCL) Intervention [ Time Frame: From the last assessment prior to BCL intervention to the end of BCL intervention, up to 38 weeks ]
    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).

  11. Time to Ocular Side Effect (OSE) Symptom Resolution After Drug Discontinuation (Reversibility) [ Time Frame: From the first dose of study drug until 49 days after last depatuxizumab mafodotin administration, up to 47 weeks ]
    The time from discontinuation of depatuxizumab mafodotin to OSE symptom resolution (reversibility) was to be recorded.

  12. Time to Re-initiation of Depatuxizumab Mafodotin After Dose Interruption [ Time Frame: Up to 9 months ]
    The time from dose interruption until re-initiation or permanent discontinuation of depatuxizumab mafodotin was to be recorded.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03419403


Locations
Show Show 22 study locations
Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie
  Study Documents (Full-Text)

Documents provided by AbbVie:
Study Protocol  [PDF] May 28, 2019
Statistical Analysis Plan  [PDF] April 1, 2020

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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03419403    
Other Study ID Numbers: M16-534
2017-003171-64 ( EudraCT Number )
First Posted: February 5, 2018    Key Record Dates
Results First Posted: April 14, 2021
Last Update Posted: April 14, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (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.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

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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
Keywords provided by AbbVie:
Glioblastoma Multiforme (GBM)
Cancer
Chemoradiation therapy
Epidermal growth factor receptor-amplified glioblastoma
Radiation
Temozolomide
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Vasoconstrictor Agents
Ophthalmic Solutions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Pharmaceutical Solutions