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A Study for Management of Ocular Side Effects in Subjects With Glioblastoma Receiving Depatuxizumab Mafodotin

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ClinicalTrials.gov Identifier: NCT03419403
Recruitment Status : Recruiting
First Posted : February 2, 2018
Last Update Posted : November 2, 2018
Sponsor:
Information provided by (Responsible Party):
AbbVie

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]).

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Drug: Steroid eye drop Drug: Ophthalmic steroid ointment Radiation: Radiation Drug: Temozolomide Drug: depatuxizumab mafodotin Other: cold compress Drug: Vasoconstrictor eye drop Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 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 19, 2018
Estimated Primary Completion Date : September 16, 2019
Estimated Study Completion Date : November 21, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: Steroid eye drop
solution, eye drop

Radiation: Radiation
radiation

Drug: Temozolomide
oral

Drug: depatuxizumab mafodotin
infusion
Other Name: ABT-414

Other: cold compress
cold compress

Drug: Vasoconstrictor eye drop
solution, eye drop

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.
Drug: Steroid eye drop
solution, eye drop

Radiation: Radiation
radiation

Drug: Temozolomide
oral

Drug: depatuxizumab mafodotin
infusion
Other Name: ABT-414

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.
Drug: Steroid eye drop
solution, eye drop

Drug: Ophthalmic steroid ointment
ointment

Radiation: Radiation
radiation

Drug: Temozolomide
oral

Drug: depatuxizumab mafodotin
infusion
Other Name: ABT-414

Other: cold compress
cold compress

Drug: Vasoconstrictor eye drop
solution, eye drop




Primary Outcome Measures :
  1. Participants who Require a Change in Ocular Side Effect (OSE) Management [ Time Frame: Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin ]
    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.


Secondary Outcome Measures :
  1. Cumulative Dose of Depatuxizumab Mafodotin [ Time Frame: Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin ]
    Cumulative dose of depatuxizumab mafodotin administered (mg/kg).

  2. Change from Baseline In Logarithm of the Minimum Angle of Resolution (LogMAR) Scale after Bandage Contact Lenses (BCL) Intervention [ Time Frame: Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin ]
    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.

  3. Time to OSE Symptom Resolution after Drug Discontinuation (reversibility) [ Time Frame: Up to approximately 3 years after initial dose of depatuxizumab mafodotin ]
    Time from discontinuation of depatuxizumab mafodotin to OSE symptom resolution (reversibility).

  4. Time to BCL Intervention [ Time Frame: Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin ]
    Time to initiation of bandage contact lenses (BCL) intervention.

  5. Participants that recover to <3-line decline from Baseline (<= +0.3 LogMAR) in visual acuity after BCL Intervention [ Time Frame: Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin ]
    Recovery is defined as return to <3-line decline from baseline (<= +0.3 LogMAR) in visual acuity after BCL intervention.

  6. Corneal Epithelial Adverse Event (CEAE) Grade [ Time Frame: Up to approximately 3 years after initial dose of depatuxizumab mafodotin ]
    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).

  7. Time to Re-initiation of Depatuxizumab Mafodotin after Dose Interruption [ Time Frame: Up to approximately 3 years after initial dose of depatuxizumab mafodotin ]
    Time from dose interruption until re-initiation or permanent discontinuation of depatuxizumab mafodotin.

  8. Participants with Depatuxizumab Mafodotin Dose Interruptions due to OSEs [ Time Frame: Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin ]
    Participants with dose interruptions of depatuxizumab mafodotin due to ocular side effects (OSEs).

  9. Participants with Depatuxizumab Mafodotin Dose Reductions due to OSEs [ Time Frame: Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin ]
    Dose reductions of depatuxizumab mafodotin initiated due to OSEs.

  10. Maximum Change from Baseline on LogMAR Scale [ Time Frame: Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin ]
    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.



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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:

  • 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) prior to 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).

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


Contacts
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

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Sponsors and Collaborators
AbbVie
Investigators
Study Director: AbbVie Inc. AbbVie

Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03419403     History of Changes
Other Study ID Numbers: M16-534
2017-003171-64 ( EudraCT Number )
First Posted: February 2, 2018    Key Record Dates
Last Update Posted: November 2, 2018
Last Verified: October 2018
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)
Analytic Code
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

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:
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
Ophthalmic Solutions
Vasoconstrictor Agents
Antibodies, Monoclonal
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Pharmaceutical Solutions
Immunologic Factors
Physiological Effects of Drugs