Phase 3b Study for Management of Ocular Side Effects in Subjects With EGFR-amplified Glioblastoma Receiving Depatuxizumab Mafodotin (ABT-414)
| Registry | NCT03419403 |
|---|---|
| Status | Terminated - The study was terminated because clinical development of depatuxizumab mafodotin in glioblastoma was stopped due to lack of survival benefit. |
| Phase | Phase 3 |
| Study type | Interventional; randomized, parallel, masking: none, treatment |
| Enrollment | 40 (Actual) |
| Sponsor | AbbVie (Industry) |
| Conditions | Glioblastoma Multiforme |
| Interventions | Steroid eye drops, Vasoconstrictor eye drops, Cold compress, Ophthalmic steroid ointment, Depatuxizumab mafodotin, Temozolomide, Radiation (Drug, other, radiation) |
| Dates | start 2018-07-30, primary completion 2019-09-05, completion 2020-03-03, first posted 2018-02-05, last updated 2021-04-14 |
| Locations | 22 sites in United States, Australia, Germany, Netherlands, United Kingdom |
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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).
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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Standard Steroids | Experimental | Drug: Steroid eye drops; Drug: Depatuxizumab mafodotin; Drug: Temozolomide; Radiation: Radiation | 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 |
| Standard Steroids + Vasoconstrictor + Cold Compress | Experimental | Drug: Steroid eye drops; Drug: Vasoconstrictor eye drops; Other: Cold compress; Drug: Depatuxizumab mafodotin; Drug: Temozolomide; Radiation: Radiation | 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). |
| Enhanced Steroids + Vasoconstrictor + Cold Compress | Experimental | Drug: Steroid eye drops; Drug: Vasoconstrictor eye drops; Other: Cold compress; Drug: Ophthalmic steroid ointment; Drug: Depatuxizumab mafodotin; Drug: Temozolomide; Radiation: Radiation | 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). |
Sex: All, ages: 18 Years to any
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)
| Milestone | Standard Steroids | Standard Steroids + Vasoconstrictor + Cold Compress | Enhanced Steroids + Vasoconstrictor + Cold Compress | Untreated Participants |
|---|---|---|---|---|
| Started | 14 | 12 | 12 | 2 |
| Completed | 2 | 3 | 0 | 0 |
| Not completed | 12 | 9 | 12 | 2 |
Time frame: Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 49 days after last depatuxizumab mafodotin administration, up to 47 weeks. In addition, serious adverse events and protocol-related nonserious adverse events were collected from the time the participant signed the study-specific informed consent.
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|---|---|---|
| Standard Steroids | 1/14 (7.1%) | 6/14 (42.9%) | 14/14 (100.0%) |
| Standard Steroids + Vasoconstrictor + Cold Compress | 1/12 (8.3%) | 4/12 (33.3%) | 12/12 (100.0%) |
| Enhanced Steroids + Vasoconstrictor + Cold Compress | 1/12 (8.3%) | 4/12 (33.3%) | 12/12 (100.0%) |
| Term | Organ system | Standard Steroids | Standard Steroids + Vasoconstrictor + Cold Compress | Enhanced Steroids + Vasoconstrictor + Cold Compress |
|---|---|---|---|---|
| FEBRILE NEUTROPENIA | Blood and lymphatic system disorders | 0/14 | 1/12 | 0/12 |
| THROMBOCYTOPENIA | Blood and lymphatic system disorders | 1/14 | 1/12 | 1/12 |
| ULCERATIVE KERATITIS | Eye disorders | 0/14 | 1/12 | 0/12 |
| VOMITING | Gastrointestinal disorders | 1/14 | 0/12 | 0/12 |
| PYREXIA | General disorders | 1/14 | 0/12 | 1/12 |
| CELLULITIS | Infections and infestations | 1/14 | 0/12 | 0/12 |
| EYE INFECTION | Infections and infestations | 0/14 | 1/12 | 0/12 |
| LOWER RESPIRATORY TRACT INFECTION | Infections and infestations | 1/14 | 0/12 | 0/12 |
| PNEUMONIA | Infections and infestations | 0/14 | 1/12 | 0/12 |
| ALANINE AMINOTRANSFERASE INCREASED | Investigations | 1/14 | 0/12 | 0/12 |
| MALIGNANT NEOPLASM PROGRESSION | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/14 | 0/12 | 0/12 |
| TUMOUR PSEUDOPROGRESSION | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/14 | 0/12 | 1/12 |
| HEADACHE | Nervous system disorders | 0/14 | 0/12 | 1/12 |
| HEMIPARESIS | Nervous system disorders | 1/14 | 1/12 | 1/12 |
| SEIZURE | Nervous system disorders | 1/14 | 1/12 | 0/12 |
| STATUS EPILEPTICUS | Nervous system disorders | 0/14 | 0/12 | 1/12 |
| PULMONARY EMBOLISM | Respiratory, thoracic and mediastinal disorders | 1/14 | 0/12 | 0/12 |
| DEEP VEIN THROMBOSIS | Vascular disorders | 1/14 | 0/12 | 0/12 |
| HAEMATOMA | Vascular disorders | 1/14 | 0/12 | 0/12 |
| Term | Organ system | Standard Steroids | Standard Steroids + Vasoconstrictor + Cold Compress | Enhanced Steroids + Vasoconstrictor + Cold Compress |
|---|---|---|---|---|
| ANAEMIA | Blood and lymphatic system disorders | 1/14 | 2/12 | 1/12 |
| LEUKOPENIA | Blood and lymphatic system disorders | 0/14 | 0/12 | 1/12 |
| LYMPHOPENIA | Blood and lymphatic system disorders | 0/14 | 1/12 | 0/12 |
| NEUTROPENIA | Blood and lymphatic system disorders | 1/14 | 1/12 | 1/12 |
| THROMBOCYTOPENIA | Blood and lymphatic system disorders | 3/14 | 5/12 | 3/12 |
| CARDIOMEGALY | Cardiac disorders | 0/14 | 1/12 | 0/12 |
| TACHYCARDIA | Cardiac disorders | 0/14 | 1/12 | 1/12 |
| EAR PAIN | Ear and labyrinth disorders | 1/14 | 0/12 | 0/12 |
| HYPOACUSIS | Ear and labyrinth disorders | 0/14 | 1/12 | 0/12 |
| ACQUIRED EPIBLEPHARON | Eye disorders | 0/14 | 0/12 | 1/12 |
| CONJUNCTIVITIS ALLERGIC | Eye disorders | 0/14 | 0/12 | 1/12 |
| DIPLOPIA | Eye disorders | 0/14 | 1/12 | 0/12 |
| DRY EYE | Eye disorders | 0/14 | 1/12 | 0/12 |
| EYELID PTOSIS | Eye disorders | 0/14 | 0/12 | 1/12 |
| FOREIGN BODY SENSATION IN EYES | Eye disorders | 0/14 | 1/12 | 0/12 |
| VISION BLURRED | Eye disorders | 0/14 | 1/12 | 0/12 |
| ABDOMINAL DISTENSION | Gastrointestinal disorders | 1/14 | 0/12 | 0/12 |
| ANAL INCONTINENCE | Gastrointestinal disorders | 0/14 | 1/12 | 0/12 |
| CONSTIPATION | Gastrointestinal disorders | 5/14 | 4/12 | 2/12 |
| DIARRHOEA | Gastrointestinal disorders | 1/14 | 1/12 | 0/12 |
| DRY MOUTH | Gastrointestinal disorders | 0/14 | 1/12 | 0/12 |
| DUODENAL ULCER | Gastrointestinal disorders | 0/14 | 0/12 | 1/12 |
| DYSPHAGIA | Gastrointestinal disorders | 1/14 | 0/12 | 0/12 |
| GASTRITIS EROSIVE | Gastrointestinal disorders | 0/14 | 0/12 | 1/12 |
| HAEMORRHOIDAL HAEMORRHAGE | Gastrointestinal disorders | 0/14 | 2/12 | 0/12 |
| HAEMORRHOIDS | Gastrointestinal disorders | 0/14 | 1/12 | 0/12 |
| MOUTH ULCERATION | Gastrointestinal disorders | 0/14 | 1/12 | 0/12 |
| NAUSEA | Gastrointestinal disorders | 6/14 | 6/12 | 3/12 |
| STOMATITIS | Gastrointestinal disorders | 0/14 | 1/12 | 0/12 |
| VOMITING | Gastrointestinal disorders | 5/14 | 1/12 | 1/12 |
| ASTHENIA | General disorders | 1/14 | 1/12 | 0/12 |
| CHEST PAIN | General disorders | 0/14 | 1/12 | 0/12 |
| FATIGUE | General disorders | 6/14 | 9/12 | 7/12 |
| INFLUENZA LIKE ILLNESS | General disorders | 0/14 | 0/12 | 1/12 |
| OEDEMA PERIPHERAL | General disorders | 0/14 | 1/12 | 0/12 |
| PYREXIA | General disorders | 1/14 | 0/12 | 0/12 |
| DRUG-INDUCED LIVER INJURY | Hepatobiliary disorders | 0/14 | 2/12 | 0/12 |
| HYPERSENSITIVITY | Immune system disorders | 0/14 | 1/12 | 0/12 |
| BALANITIS CANDIDA | Infections and infestations | 1/14 | 0/12 | 0/12 |
| NASOPHARYNGITIS | Infections and infestations | 1/14 | 0/12 | 0/12 |
| ORAL CANDIDIASIS | Infections and infestations | 1/14 | 0/12 | 0/12 |
| ORAL HERPES | Infections and infestations | 1/14 | 0/12 | 0/12 |
| SINUSITIS | Infections and infestations | 1/14 | 0/12 | 1/12 |
| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | 0/14 | 1/12 | 0/12 |
| URINARY TRACT INFECTION | Infections and infestations | 0/14 | 1/12 | 0/12 |
| ARTHROPOD BITE | Injury, poisoning and procedural complications | 0/14 | 0/12 | 1/12 |
| CORNEAL ABRASION | Injury, poisoning and procedural complications | 1/14 | 0/12 | 0/12 |
| FALL | Injury, poisoning and procedural complications | 2/14 | 0/12 | 1/12 |
| INCISION SITE PAIN | Injury, poisoning and procedural complications | 0/14 | 0/12 | 1/12 |
| INFUSION RELATED REACTION | Injury, poisoning and procedural complications | 1/14 | 0/12 | 1/12 |
| RADIATION NECROSIS | Injury, poisoning and procedural complications | 0/14 | 1/12 | 0/12 |
| RADIATION SKIN INJURY | Injury, poisoning and procedural complications | 2/14 | 1/12 | 0/12 |
| SKIN ABRASION | Injury, poisoning and procedural complications | 1/14 | 0/12 | 0/12 |
| ALANINE AMINOTRANSFERASE INCREASED | Investigations | 2/14 | 5/12 | 3/12 |
| ASPARTATE AMINOTRANSFERASE INCREASED | Investigations | 4/14 | 2/12 | 2/12 |
| BLOOD BILIRUBIN ABNORMAL | Investigations | 1/14 | 0/12 | 0/12 |
| BLOOD CALCIUM INCREASED | Investigations | 1/14 | 0/12 | 0/12 |
| BLOOD CREATININE INCREASED | Investigations | 1/14 | 0/12 | 0/12 |
| BLOOD PHOSPHORUS DECREASED | Investigations | 0/14 | 1/12 | 0/12 |
| CARDIAC MURMUR | Investigations | 0/14 | 0/12 | 1/12 |
60 more terms not shown.
| Facility | City | Country | Status |
|---|---|---|---|
| Usc /Id# 164235 | Los Angeles, California | United States | |
| Moffitt Cancer Center /ID# 164234 | Tampa, Florida | United States | |
| Rush University Medical Center /ID# 171003 | Chicago, Illinois | United States | |
| Northshore University Health System-Evanston /ID# 164221 | Evanston, Illinois | United States | |
| CDH-Delnor Health System /ID# 169909 | Warrenville, Illinois | United States | |
| Columbia University Medical Center /ID# 164220 | New York, New York | United States | |
| Levine Cancer Ins, Carolina Me /ID# 171271 | Charlotte, North Carolina | United States | |
| UT Health Science Ctr-Houston /ID# 164223 | Houston, Texas | United States | |
| Baylor Scott & White Medical Center- Temple /ID# 170792 | Temple, Texas | United States | |
| Royal North Shore Hospital /ID# 169673 | Saint Leonards, New South Wales | Australia | |
| Calvary Mater Newcastle /ID# 169672 | Waratah, New South Wales | Australia | |
| Royal Brisbane and Women's Hospital /ID# 169674 | Herston, Queensland | Australia | |
| Austin Hospital /ID# 169671 | Heidelberg, Victoria | Australia | |
| Universitaetsklinik Heidelberg /ID# 169970 | Heidelberg, Baden-Wurttemberg | Germany | |
| Universitaetsklinikum Leipzig /ID# 169969 | Leipzig, Saxony | Germany | |
| Klinikum Univ. Regensburg /ID# 169963 | Regensburg | Germany | |
| Universitatsklinikum Tubingen /ID# 169965 | Tübingen | Germany | |
| Vrije Universiteit Medisch Centrum /ID# 170152 | Amsterdam | Netherlands | |
| Universitair Medisch Centrum Utrecht /ID# 170149 | Utrecht | Netherlands | |
| Guy's and St Thomas' NHS Found /ID# 207752 | London, London, City of | United Kingdom | |
| Queen Elizabeth Hospital - BIRMINGHAM /ID# 200657 | Birmingham | United Kingdom | |
| Castle Hill Hospital /ID# 200662 | Cottingham | United Kingdom |
NIH grants: 2017