E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
EGFR-Amplified Newly diagnosed glioblastoma |
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E.1.1.1 | Medical condition in easily understood language |
Glioblastoma, a rare and aggressive type of brain tumor. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018336 |
E.1.2 | Term | Glioblastoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Estimate the percentage of subjects in each prophylactic treatment arm who require a change in Ocular Side Effects (OSE) management due to inadequate control of Ocular Side Effects.
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E.2.2 | Secondary objectives of the trial |
Maximum Change from Baseline on LogMAR Scale |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
There is an optional sub-study. Biomarker samples (optional tumor tissue samples from the subjects' initial surgery and optional post-mortem tumor samples and corneal tissue samples) will be collected.
The sub-studies are included in the main protocol with additional consents required for participation in these sub-studies |
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E.3 | Principal inclusion criteria |
• Participant has a histologically proven, World Health Organization (WHO) grade IV glioblastoma 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 |
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E.4 | Principal exclusion criteria |
• Participants with newly diagnosed Glioblastoma: 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 Temozolomide or dacarbazine.
• Participant has received anti-cancer therapy (including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic, or any investigational therapy) prior to 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 infection with hepatitis B virus (i.e., hepatitis B surface antigen) or hepatitis C virus (i.e., positive for hepatitis C antibody). Subjects who have a history of hepatitis C who have documented cures after anti-viral therapy may be enrolled. Subjects with confirmed positive test result for human immunodeficiency virus (HIV), with CD4
count < 200 cells/microliter are excluded. Note that subjects who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to registration, as the treatments involved in this protocol may be significantly immunosuppressive. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is defined as the percentage of subjects with either a ≥ 3-line decline from baseline (≥ + 0.3 on LogMAR scale) in visual acuity (with baseline correction), or ≥ Grade 3 Ocular Side Effects severity on the Corneal Epithelial Adverse Event (CEAE) scale, either of which will indicate inadequate control of ocular side effects requiring a change in Ocular side effects management strategy.
Unless otherwise noted, visual acuity will be measured using baseline
correction, which will be determined at the screening ophthalmology
visit and used to assess visual acuity at all remaining ophthalmology
visits, for measuring changes in visual acuity and for determining the
visual acuity component of the primary endpoint. Details on determining
baseline correction are provided in the operations manual. The primary endpoint will be assessed over 8 weeks after initiation of depatuxizumab mafodotin treatment.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin |
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E.5.2 | Secondary end point(s) |
The Logarithm of the Minimum Angle of Resolution (LogMAR) scale is the validated tool used in ophthalmology clinical trials to evaluate change in visual acuity. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to approximately 18 weeks after initial dose of depatuxizumab mafodotin |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Phase III B: Depatuxizumab Mafodotin is known to cause ocular side effects.
This study is a safety trial designed to test several ocular side effect management strategies. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Denmark |
Germany |
Netherlands |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |