This exploratory study is designed to evaluate several depatuxizumab mafodotin-related OSE management strategies.The main objective of this trial is to estimate the percentage of subjects in each prophylactic treatment arm who require a change in…
ID
Source
Brief title
Condition
- Eye disorders NEC
- Nervous system neoplasms malignant and unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 OSE severity on the Corneal Epithelial
Adverse Event (CEAE) scale, either of which will indicate inadequate control of
OSEs requiring a change in OSE 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.
Secondary outcome
The Logarithm of the Minimum Angle of Resolution (LogMAR) scale is used to
measure visual acuity. The CEAE scale will be used to measure the severity of
OSEs. These will be followed over the course of treatment.
Background summary
Depatuxizumab mafodotin is being investigated in late phase clinical trials of
patients with glioblastoma (GBM) that demonstrate epidermal growth factor
receptor (EGFR) amplification. The dose-limiting toxicities (DLTs) observed
after depatuxizumab mafodotin exposure have been limited to ocular side effects
(OSEs). This exploratory study is designed to evaluate several depatuxizumab
mafodotin-related OSE management strategies.
Study objective
This exploratory study is designed to evaluate several depatuxizumab
mafodotin-related OSE management strategies.
The main objective of this trial is to 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.
The secondary objective of this trial is to assess the effects of intervention
with bandage contact lenses (BCL) on visual acuity and OSE symptom severity for
those subjects who require intervention due to inadequate control of OSEs.
Study design
This is a Phase 3b open-label, randomized study. All subjects will receive
depatuxizumab mafodotin treatment in addition to current standard-of-care
treatment of concomitant radiation therapy/temozolomide (RT/TMZ) and adjuvant
TMZ. Subjects will be randomized 1:1:1 to one of the 3 opthalmologic
prophylactic treatment arms.
Intervention
Subjects will receive depatuxizumab mafodotin during the chemoradiation phase
(consisting of radiation and temozolomide [RT/TMZ]) and depatuxizumab mafodotin
during adjuvant therapy with TMZ. Depatuxizumab mafodotin will be administered
every 2 weeks during standard 6-week RT/TMZ therapy, followed by a 4-week
recovery period. During adjuvant therapy, depatuxizumab mafodotin will be
administered every 2 weeks for 12 cycles (28 days/cycle).
Subjects will be randomized to one of 3 prophylactic ophthalmologic treatments
(Standard Steroids, Standard Steroids/Vasoconstrictors, or Enhanced
Steroids/Vasoconstrictors).
Study burden and risks
The subjects participating in the study will have a higher burden because of
participation in the trial. Subject will be visiting the hospital more
frequently. During these visits study procedures will be performed including
blood and urine sampling, ophthalmology exam, physical exam, vital signs and
filling in questionnaires. Subject will also be tested for significant heart
conditions and pregnancy.
Next to this the subjects will receive Depatux-M and prophylactic eye treatment
in additional to the standard treatment.
Risks in this study include adverse events from Depatux-M and the prophylactic
eye treatment and adverse events related to the standard treatment (radiation
treatment and TMZ). Depatux-M has been tested in a limited number of people, so
the side effects are only partially known. Eye problems are the main side
effects caused by Depatux-M. Other most frequently reported side effects (>= 10%
of all studies reported) in Depatux-M studies were: fatigue or decreased
energy, decreased appetite, headache and changes in the blood tests that show
possible liver damage. Steroid eye drops used as part of the prophylactic eye
treatments can increase pressure in the eye, which over time could lead to
visual impairment, and increase the risk of eye infections.
The current data of Depatux-M and the lack of an effective treatment
alternative reflect an acceptable rationale and risk for treating adult
patients with cancer that has a moderate to high level of EGFR expression with
Depatux-M in the context of a clinical trial.
Wegalaan 9
Hoofddorp 2132 JD
NL
Wegalaan 9
Hoofddorp 2132 JD
NL
Listed location countries
Age
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;•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.
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-003171-64-NL |
| ClinicalTrials.gov | NCT03419403 |
| CCMO | NL64716.041.18 |