Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas
Study Purpose
This study was conducted to evaluate the efficacy and safety of depatuxizumab mafodotin (ABT-414) alone or with temozolomide versus temozolomide or lomustine alone in adult participants with recurrent glioblastoma. The study also included a substudy to evaluate safety, tolerability and pharmacokinetics of ABT-414 in a pediatric population.
Recruitment Criteria
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Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
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Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
| Eligible Ages | N/A - 99 Years |
| Gender | All |
Inclusion Criteria:
Adult participants (greater than or equal to 18 years old):- - Histologically confirmed de novo (primary) glioblastoma with unequivocal tumor progression or recurrence.
- - In case of testing at the time of first progression: either at least 3 months after the end of radiotherapy or have tumor progression that is clearly outside the radiation field or have tumor progression unequivocally proven by surgery/biopsy.
- - Absence of any psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule; such conditions should be assessed with the patient before registration in the trial.
- - Availability of adequate biological material (formalin-fixed paraffin embedded [FFPE] tumor) for central testing of Epithelial Growth Factor Receptor (EGFR) amplification.
- - Presence of EGFR amplification confirmed by central assessment; participants with undetermined EGFR status are excluded.
- - World Health Organization (WHO) Performance status 0 - 2.
- - No more than one line of chemotherapy (concurrent and adjuvant Temozolomide based chemotherapy including in combination with another investigational agent is considered one line of chemotherapy).
- - Post surgery MRI within 48 hours following surgery, however an MRI scan has to be done within 2 weeks prior to randomization.
- - Surgery completed at least 2 weeks before randomization and patients should have fully recovered as assessed by investigators.
- - Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula.
- - Liver function: bilirubin < 1.5× upper limit of the normal range (ULN), alkaline phosphatase and transaminases (ASAT) < 2.5× ULN.
- - Histologically proven high grade glioma (HGG: WHO grade III glioma [e.
- - Must either have recurrent/progressive tumor or, if newly diagnosed, have completed any planned radiation therapy at least 4 weeks prior to first dose of ABT-414.
- - The tumor tissue must have been determined to have EGFR amplification, (by local or other testing service).
- - Availability of adequate biological material for retrospective confirmatory central testing of EGFR amplification.
- - Participant has sufficiently recovered from previous therapy.
- - Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula for pediatric patients ≥12 years of age and estimated glomerular filtration rate ≥ 30 mL/min/1.73 m^2 by modified Schwartz equation for pediatric patients < 12 years of age.
- - Liver function: Total bilirubin ≤ 1.5× upper limit of the normal range (ULN), Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) <= 3× ULN.
Exclusion Criteria:
Adult population (greater than or equal to 18 years old):- - Prior treatment with nitrosoureas.
- - Prior treatment with bevacizumab.
- - Previous exposure to Epithelial Growth Factor Receptor (EGFR) targeted agents, including EGFRvIII targeting agents.
- - Prior discontinuation of temozolomide chemotherapy for toxicity reasons.
- - Prior Radiation Therapy (RT) with a dose over 65 Gy to the brain, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven.
- - Previous other malignancies, except for any previous malignancy which was treated with curative intent more than 5 years prior to randomization, and except for adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of the skin or carcinoma in situ of the cervix.
- - Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization.
- - No history of wheat allergies and Coeliac disease.
- - No EIAED, patients who require anti-convulsant therapy must be taking non-enzyme inducing antiepileptic drugs (non-EIAED).
- - (For recurrent disease) No prior RT with a dose over 65 Gy to the brain, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven.
- - No current or recent (within 4 weeks or 5 half-lives [whichever is shorter] before enrollment) treatment with another investigational drug.
- - Female participants of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization.
Trial Details
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Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT02343406 |
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Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 2 |
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Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
AbbVie |
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Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
AbbVie Inc. |
| Principal Investigator Affiliation | AbbVie |
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Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Industry, Other |
| Overall Status | Completed |
| Countries | Australia, Austria, Belgium, Canada, Czechia, Finland, France, Germany, Hungary, Ireland, Italy, Korea, Republic of, Mexico, Netherlands, Poland, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States |
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Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Glioblastoma |
The study objectives were to assess whether depatuxizumab mafodotin (ABT-414) alone or in combination with temozolomide (TMZ) improved overall survival (OS), progression-free survival (PFS), tumor response, quality of life, neurological deterioration-free survival (NDFS), and steroid use compared to standard treatment with lomustine single agent or TMZ re-challenge in adult subjects ≥ 18 years of age with centrally-confirmed recurrent epidermal growth factor receptor (EGFR)-amplified glioblastoma. The safety, pharmacokinetics, and efficacy of depatuxizumab mafodotin in children <18 years of age was evaluated in a pediatric substudy. The EMEA-001732-PIP02-15 pediatric investigation plan was withdrawn on 07 July 2019 due to the discontinuation of the depatuxizumab mafodotin research program.
Arms
Experimental: ABT-414/temozolomide
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants
Experimental: ABT-414_adult
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants
Active Comparator: Control_lomustine
Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year.
Active Comparator: Control_ temozolomide
Adult participants relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met.
Experimental: ABT-414_ pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Interventions
Drug: - Depatuxizumab mafodotin
Adults: intravenous administration (1.25 mg/kg or 1.0 mg/kg body weight) over 30 to 40 minutes once every 2 weeks until one of the treatment withdrawal criteria was met. The dose was 1.25 mg/kg in the original protocol (Version 1) and Version 2, Amendment 1, and was lowered to 1.0 mg/kg in protocol Version 3, Amendment 2. Pediatric participants: Intravenous administration (1.0 mg/kg body weight for those who were 6 to 17 years old at the date of first dose, or 1.3 mg/kg for those who were 0 to 5 years old) over 30 to 40 minutes or as directed by the guidelines once every 2 weeks until one of the treatment withdrawal criteria was met, for a maximum of one year. If used in combination with temozolomide, depatuxizumab mafodotin was dosed on Day 1 and Day 15 of the TMZ cycle (assuming a standard regimen of 200 mg/m^2/day for 5 days of each 28-day cycle; for other TMZ schedules, timing of the depatuxizumab mafodotin dosing schedule were to be discussed with the medical monitor).
Drug: - Temozolomide
Capsules administered orally, 150 mg/m^2 on Days 1-5 for the first 28-day cycle, with dose escalation to 200 mg/m^2 in subsequent cycles in case of adequate tolerance until one of the treatment withdrawal criteria was met.
Drug: - Lomustine
Capsules administered orally, 110 mg/m^2 on Day 1 of every 42-day treatment period. Treatment continued until one of the treatment withdrawal criteria was met, for a maximum of one year.
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Address
Lucile Packard Children's Hosp /ID# 153678
Palo Alto, California, 34304
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Address
Children's Hospital Colorado /ID# 153677
Aurora, Colorado, 80045
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Address
Univ of Colorado Cancer Center /ID# 134882
Aurora, Colorado, 80045
Status
Address
Sarah Cannon Research Institute at HealthONE - Denver /ID# 141798
Denver, Colorado, 80218
Status
Address
Rush University Medical Center /ID# 137542
Chicago, Illinois, 60612
Status
Address
Dana-Farber Cancer Institute /ID# 154210
Boston, Massachusetts, 02215
Status
Address
Long Island Brain Tumor Center /ID# 134496
Lake Success, New York, 11042
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Address
Weill Cornell Medicine /ID# 152656
New York, New York, 10032-3725
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Address
Cleveland Clinic Main Campus /ID# 137540
Cleveland, Ohio, 44195
Status
Address
University of Pittsburgh MC /ID# 134491
Pittsburgh, Pennsylvania, 15260
Status
Address
Tennessee Oncology, PLLC /ID# 134492
Nashville, Tennessee, 37203
Status
Address
UT Southwestern Medical Center /ID# 136718
Dallas, Texas, 75390-7208
Status
Address
Swedish Medical Center /ID# 136719
Seattle, Washington, 98104
International Sites
Status
Address
Port Macquarie Base Hospital /ID# 134569
Port Macquarie, New South Wales, 2444
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Address
Sydney Children's Hospital /ID# 153533
Randwick, New South Wales, 2031
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Address
Royal North Shore Hospital /ID# 147092
Saint Leonards, New South Wales, 2065
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Address
Calvary Mater Newcastle /ID# 134570
Waratah, New South Wales, 2298
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Address
Southern Medical Day Care Ctr /ID# 134495
Wollongong, New South Wales, 2500
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Address
Royal Brisbane and Women's Hospital /ID# 147091
Herston, Queensland, 4029
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Address
Royal Adelaide Hospital /ID# 135208
Adelaide, South Australia, 5000
Status
Address
Royal Hobart Hospital /ID# 135209
Hobart, Tasmania, 7000
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Address
Barwon Health University Hospital Geelong /ID# 134493
Geelong, Victoria, 3220
Status
Address
Royal Children's Hospital /ID# 157624
Melbourne, Victoria, 3052
Status
Address
University Hospital St. Polten /ID# 139070
St. Pölten, Niederoesterreich, 3100
Status
Address
LKH-Univ. Klinikum Graz /ID# 139071
Graz, , 8036
Status
Address
Kepler Universitätsklinikum GmbH - Neuromed Campus /ID# 139068
Linz, , 4020
Status
Address
Cliniques Universitaires Saint Luc /ID# 139391
Woluwe-Saint-Lambert, Bruxelles-Capitale, 1200
Status
Address
Grand Hôpital de Charleroi /ID# 139342
Charleroi, Hainaut, 6000
Status
Address
UZ Gent /ID# 152944
Gent, Oost-Vlaanderen, 9000
Status
Address
AZ St-Jan Brugge-Oostende AV /ID# 137927
Brugge, West-Vlaanderen, 8000
Status
Address
ZNA Middelheim /ID# 137926
Antwerp, , 2020
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Address
UZ Leuven /ID# 137925
Leuven, , 3000
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Address
Montreal Neurological Institut /ID# 136309
Montreal, Quebec, H3A 2B4
Status
Address
Fakultni Nemocnice v Motole /ID# 139509
Prague 5, Praha 5, 150 06
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Address
Masarykuv onkologikcy ustav /ID# 139508
Brno, , 656 53
Status
Address
FN Hradec Kralove /ID# 139510
Hradec Kralove, , 500 05
Status
Address
Univ Hosp Ostrava-Poruba /ID# 139507
Ostrava, , 708 52
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Address
Helsinki Univ Central Hospital /ID# 140078
Helsinki, , 00290
Status
Address
Helsinki Univ Central Hospital /ID# 153069
Helsinki, , 00290
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Address
Turku University Hospital /ID# 140861
Turku, , 20520
Status
Address
CHRU Lille - Hôpital Claude Huriez /ID# 137916
Lille CEDEX, Hauts-de-France, 59045
Status
Address
Centre Oscar Lambret /ID# 169619
Lille, Hauts-de-France, 59020
Status
Address
CHU-Hopital Avicenne /ID# 137910
Bobigny, Ile-de-France, 93000
Status
Address
Gustave Roussy /ID# 137912
Villejuif, Ile-de-France, 94805
Status
Address
Institut de Cancer de l'Ouest /ID# 137914
St Herblain CEDEX, Loire-Atlantique, 44805
Status
Address
Hopital de la Timone /ID# 137911
Marseille CEDEX 05, Provence-Alpes-Cote-d Azur, 13385
Status
Address
CHU de Nice /ID# 137917
Nice CEDEX 1, Provence-Alpes-Cote-d Azur, 06002
Status
Address
Centre Leon Berard /ID# 137918
Lyon CEDEX 08, Rhone, 69373
Status
Address
Institut de Cancer de l'Ouest /ID# 137909
Angers, , 49055
Status
Address
Hospices Civils de Lyon /ID# 137913
Bron, , 69500
Status
Address
Hopital Pitie Salpetriere /ID# 145887
Paris, , 75651
Status
Address
Universitaetsklinik Heidelberg /ID# 137924
Heidelberg, Baden-Wuerttemberg, 69120
Status
Address
Universitatsklinik Regensburg /ID# 137920
Ratisbon, Bayern, 93053
Status
Address
Univ Klinik Eppendorf Hamburg /ID# 137921
Hamburg, , 20246
Status
Address
LMU Klinikum der Universität München /ID# 137922
Munich, , 80337
Status
Address
Universitatsklinikum Tubingen /ID# 137923
Tuebingen, , 72076
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Address
Pecsi Tudomanyegyetem /ID# 136111
Pécs, Pecs, 7624
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Address
Semmelweis Egyetem /ID# 152578
Budapest, , 1085
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Address
National Institute of Oncology /ID# 135970
Budapest, , 1122
Status
Address
Orszagos Klinikai Idegtudomany /ID# 135971
Budapest, , 1145
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Address
Debreceni Egyetem Klinikai Központ /ID# 135969
Debrecen, , 4032
Status
Address
Cork University Hospital /ID# 136828
Cork, , T12 E8YV
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Address
Beaumont Hospital /ID# 136829
Dublin, , D09 XR63
Status
Address
Ospedale Bellaria.Azienda USL IRCCS.Istituto delle Scienze Neurologiche di Bolog /ID# 138335
Bologna, , 40139
Status
Address
Ospedale Generale di Bolzano /ID# 138338
Bolzano, , 39100
Status
Address
Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 140395
Milan, , 20133
Status
Address
Istituto Oncologico Veneto /ID# 138336
Padova, , 35128
Status
Address
Azienda Ospedaliera Sant' Andrea /ID# 138337
Rome, , 00189
Status
Address
Seoul National Univ Bundang ho /ID# 136841
Seongnam, Gyeonggido, 13620
Status
Address
Samsung Medical Center /ID# 136842
Seoul, Seoul Teugbyeolsi, 06351
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Address
Seoul National University Hospital /ID# 136840
Seoul, , 03080
Status
Address
Hospital Zambrano Hellion /ID# 138076
San Pedro Garza García, , 66278
Status
Address
Vrije Universiteit Medisch Centrum /ID# 137221
Amsterdam, , 1081 HV
Status
Address
Universitair Medisch Centrum Groningen /ID# 138266
Groningen, , 9713 GZ
Status
Address
Erasmus Medisch Centrum /ID# 136981
Rotterdam, , 3015 CE
Status
Address
Haaglanden Medisch Centrum /ID# 137222
The Hague, , 2512 VA
Status
Address
Universitair Medisch Centrum Utrecht /ID# 137219
Utrecht, , 3584 CX
Status
Address
Prinses Maxima Centrum /ID# 204409
Utrecht, , 3584 EA
Status
Address
Uniwersyteckie Centrum Kliniczne /ID# 137919
Gdansk, Mazowieckie, 80-214
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Address
Wojewodzkie Wielospecjalistycz /ID# 137654
Lodz, , 93-509
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Address
National University Hospital /ID# 135951
Singapore, , 119074
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Address
National Cancer Ctr Singapore /ID# 135952
Singapore, , 169610
Status
Address
KK Women's & Children Hospital /ID# 153676
Singapore, , 229899
Status
Address
Instituto Catalán de Oncología (ICO) Badalona /ID# 140976
Badalona, Barcelona, 08916
Status
Address
Clinica Universitar de Navarra - Pamplona /ID# 140047
Pamplona, Navarra, Comunidad, 31008
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Address
Instituto Catalan de Oncologia (ICO) & Hosp. de Bellvitge /ID# 137688
Barcelona, , 08908
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Address
Hospital Universitario Nino /ID# 153800
Madrid, , 28009
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Address
Hosp Univ 12 de Octubre /ID# 137908
Madrid, , 28041
Status
Address
Centre Hospitalier Univ Vaudoi /ID# 137929
Lausanne, , 1011
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Address
University Hospital Zurich /ID# 137930
Zurich, , 8091
Status
Address
China Medical University Hosp /ID# 136976
Taichung City, Taichung, 40447
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Address
National Taiwan Univ Hosp /ID# 136975
Taipei City, Taipei, 10002
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Address
Taichung Veterans General Hosp /ID# 136977
Taichung City, , 40705
Status
Address
Taipei Veterans General Hosp /ID# 136974
Taipei City, , 11217
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Address
Linkou Chang Gung Memorial Ho /ID# 136944
Taoyuan City, , 33305
Status
Address
Guy's and St Thomas' NHS Found /ID# 140312
London, London, City Of, SE1 9RT
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Address
Univ Hospitals Birmingham NHS Foundation trust /ID# 136978
Birmingham, , B15 2TG
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Address
Gartnavel General Hospital /ID# 136979
Glasgow, , G12 0YN
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Address
Hull and East Yorkshire NHS /ID# 136917
Hull, , HU8 9HE
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Address
University College Hospitals /ID# 136879
London, , NW1 2BU
Status
Address
Great Ormond St Hospital NHS /ID# 153421
London, , WC1N 3JH
Status
Address
Christie NHS Foundation Trust /ID# 140313
Manchester, , M20 4BX
