GlioblastomaPhase 2INTELLANCE-2NCT02343406
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
A Phase 2 study testing Depatuxizumab mafodotin, Temozolomide and Lomustine in people with Glioblastoma, run by AbbVie at 102 sites in 21 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 99 years
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Depatuxizumab mafodotin, Temozolomide and Lomustine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 266 participants
- Where
- 102 sitesin 21 countries
- Study dates
- 17 Feb 2015to 24 Jun 2019
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 99 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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). Chemotherapy must have been completed at least 4 weeks prior to randomization.
- 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
- Pediatric sub-study participants (less than 18 years old):
- Histologically proven high grade glioma (HGG: WHO grade III glioma [e.g anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma], grade IV glioma [e.g. glioblastoma, gliosarcoma] or diffuse intrinsic pontine glioma [DIPG]).
- 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. The investigator believes that benefit of treating the pediatric subject with ABT-414 outweighs the expected risks and that this treatment is in the best interests of the pediatric subject.
- 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. Participants with Gilbert's syndrome documented in medical history may be enrolled if total bilirubin is < 3 times ULN. Not allowed are participants with known chronic liver disease and/or cirrhosis.
Who cannot join
- 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
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- 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). Patients previously on EIAED must be fully switched to non-EIAED at least 2 weeks prior to randomization.
- Pediatric sub-study (less than 18 years old):
- (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 locations and contacts
102 sites in 21 countries.
102 sites in 21 countries
United States13 sites
Children's Hospital Colorado /ID# 153677
Aurora, Colorado, 80045
Univ of Colorado Cancer Center /ID# 134882
Aurora, Colorado, 80045
Dana-Farber Cancer Institute /ID# 154210
Boston, Massachusetts, 02215
Rush University Medical Center /ID# 137542
Chicago, Illinois, 60612
Cleveland Clinic Main Campus /ID# 137540
Cleveland, Ohio, 44195
UT Southwestern Medical Center /ID# 136718
Dallas, Texas, 75390-7208
Sarah Cannon Research Institute at HealthONE - Denver /ID# 141798
Denver, Colorado, 80218
Long Island Brain Tumor Center /ID# 134496
Lake Success, New York, 11042
Tennessee Oncology, PLLC /ID# 134492
Nashville, Tennessee, 37203
Weill Cornell Medicine /ID# 152656
New York, New York, 10032-3725
Lucile Packard Children's Hosp /ID# 153678
Palo Alto, California, 34304
University of Pittsburgh MC /ID# 134491
Pittsburgh, Pennsylvania, 15260
Swedish Medical Center /ID# 136719
Seattle, Washington, 98104
France11 sites
Institut de Cancer de l'Ouest /ID# 137909
Angers, 49055
CHU-Hopital Avicenne /ID# 137910
Bobigny, Île-de-France Region, 93000
Hospices Civils de Lyon /ID# 137913
Bron, 69500
Centre Oscar Lambret /ID# 169619
Lille, Hauts-de-France, 59020
CHRU Lille - Hôpital Claude Huriez /ID# 137916
Lille, Hauts-de-France, 59045
Centre Leon Berard /ID# 137918
Lyon, Rhone, 69373
Hopital de la Timone /ID# 137911
Marseille, Provence-Alpes-Côte d'Azur Region, 13385
CHU de Nice /ID# 137917
Nice, Provence-Alpes-Côte d'Azur Region, 06002
Hopital Pitie Salpetriere /ID# 145887
Paris, 75651
Institut de Cancer de l'Ouest /ID# 137914
Saint-Herblain, Loire-Atlantique, 44805
Gustave Roussy /ID# 137912
Villejuif, Île-de-France Region, 94805
Australia10 sites
Royal Adelaide Hospital /ID# 135208
Adelaide, South Australia, 5000
Barwon Health University Hospital Geelong /ID# 134493
Geelong, Victoria, 3220
Royal Brisbane and Women's Hospital /ID# 147091
Herston, Queensland, 4029
Royal Hobart Hospital /ID# 135209
Hobart, Tasmania, 7000
Royal Children's Hospital /ID# 157624
Melbourne, Victoria, 3052
Port Macquarie Base Hospital /ID# 134569
Port Macquarie, New South Wales, 2444
Sydney Children's Hospital /ID# 153533
Randwick, New South Wales, 2031
Royal North Shore Hospital /ID# 147092
Saint Leonards, New South Wales, 2065
Calvary Mater Newcastle /ID# 134570
Waratah, New South Wales, 2298
Southern Medical Day Care Ctr /ID# 134495
Wollongong, New South Wales, 2500
United Kingdom7 sites
Univ Hospitals Birmingham NHS Foundation trust /ID# 136978
Birmingham, B15 2TG
Gartnavel General Hospital /ID# 136979
Glasgow, G12 0YN
Hull and East Yorkshire NHS /ID# 136917
Hull, HU8 9HE
Guy's and St Thomas' NHS Found /ID# 140312
London, London, City of, SE1 9RT
University College Hospitals /ID# 136879
London, NW1 2BU
Great Ormond St Hospital NHS /ID# 153421
London, WC1N 3JH
Christie NHS Foundation Trust /ID# 140313
Manchester, M20 4BX
Belgium6 sites
ZNA Middelheim /ID# 137926
Antwerp, 2020
AZ St-Jan Brugge-Oostende AV /ID# 137927
Bruges, West-Vlaanderen, 8000
Grand Hôpital de Charleroi /ID# 139342
Charleroi, Hainaut, 6000
UZ Gent /ID# 152944
Ghent, Oost-Vlaanderen, 9000
UZ Leuven /ID# 137925
Leuven, 3000
Cliniques Universitaires Saint Luc /ID# 139391
Woluwe-Saint-Lambert, Brussels Capital, 1200
Netherlands6 sites
Vrije Universiteit Medisch Centrum /ID# 137221
Amsterdam, 1081 HV
Universitair Medisch Centrum Groningen /ID# 138266
Groningen, 9713 GZ
Erasmus Medisch Centrum /ID# 136981
Rotterdam, 3015 CE
Haaglanden Medisch Centrum /ID# 137222
The Hague, 2512 VA
Universitair Medisch Centrum Utrecht /ID# 137219
Utrecht, 3584 CX
Prinses Maxima Centrum /ID# 204409
Utrecht, 3584 EA
Germany5 sites
Univ Klinik Eppendorf Hamburg /ID# 137921
Hamburg, 20246
Universitaetsklinik Heidelberg /ID# 137924
Heidelberg, Baden-Wurttemberg, 69120
LMU Klinikum der Universität München /ID# 137922
Munich, 80337
Universitatsklinik Regensburg /ID# 137920
Regensburg, Bavaria, 93053
Universitatsklinikum Tubingen /ID# 137923
Tübingen, 72076
Hungary5 sites
Semmelweis Egyetem /ID# 152578
Budapest, 1085
National Institute of Oncology /ID# 135970
Budapest, 1122
Orszagos Klinikai Idegtudomany /ID# 135971
Budapest, 1145
Debreceni Egyetem Klinikai Központ /ID# 135969
Debrecen, 4032
Pecsi Tudomanyegyetem /ID# 136111
Pécs, Pecs, 7624
Italy5 sites
Ospedale Bellaria.Azienda USL IRCCS.Istituto delle Scienze Neurologiche di Bolog /ID# 138335
Bologna, 40139
Ospedale Generale di Bolzano /ID# 138338
Bolzano, 39100
Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 140395
Milan, 20133
Istituto Oncologico Veneto /ID# 138336
Padova, 35128
Azienda Ospedaliera Sant' Andrea /ID# 138337
Rome, 00189
Spain5 sites
Instituto Catalán de Oncología (ICO) Badalona /ID# 140976
Badalona, Barcelona, 08916
Instituto Catalan de Oncologia (ICO) & Hosp. de Bellvitge /ID# 137688
Barcelona, 08908
Hospital Universitario Nino /ID# 153800
Madrid, 28009
Hosp Univ 12 de Octubre /ID# 137908
Madrid, 28041
Clinica Universitar de Navarra - Pamplona /ID# 140047
Pamplona, Navarra, Comunidad, 31008
Taiwan5 sites
China Medical University Hosp /ID# 136976
Taichung, Taichung, 40447
Taichung Veterans General Hosp /ID# 136977
Taichung, 40705
Taipei Veterans General Hosp /ID# 136974
Taipei, 11217
National Taiwan Univ Hosp /ID# 136975
Taipei City, Taipei, 10002
Linkou Chang Gung Memorial Ho /ID# 136944
Taoyuan City, 33305
Czechia4 sites
Masarykuv onkologikcy ustav /ID# 139508
Brno, 656 53
FN Hradec Kralove /ID# 139510
Hradec Králové, 500 05
Univ Hosp Ostrava-Poruba /ID# 139507
Ostrava, 708 52
Fakultni Nemocnice v Motole /ID# 139509
Prague, Praha 5, 150 06
Austria3 sites
LKH-Univ. Klinikum Graz /ID# 139071
Graz, 8036
Kepler Universitätsklinikum GmbH - Neuromed Campus /ID# 139068
Linz, 4020
University Hospital St. Polten /ID# 139070
Sankt Pölten, Lower Austria, 3100
Finland3 sites
Helsinki Univ Central Hospital /ID# 140078
Helsinki, 00290
Helsinki Univ Central Hospital /ID# 153069
Helsinki, 00290
Turku University Hospital /ID# 140861
Turku, 20520
Singapore3 sites
National University Hospital /ID# 135951
Singapore, 119074
National Cancer Ctr Singapore /ID# 135952
Singapore, 169610
KK Women's & Children Hospital /ID# 153676
Singapore, 229899
South Korea3 sites
Seoul National Univ Bundang ho /ID# 136841
Seongnam, Gyeonggido, 13620
Samsung Medical Center /ID# 136842
Seoul, Seoul Teugbyeolsi, 06351
Seoul National University Hospital /ID# 136840
Seoul, 03080
Ireland2 sites
Cork University Hospital /ID# 136828
Cork, T12 E8YV
Beaumont Hospital /ID# 136829
Dublin, D09 XR63
Poland2 sites
Uniwersyteckie Centrum Kliniczne /ID# 137919
Gdansk, Masovian Voivodeship, 80-214
Wojewodzkie Wielospecjalistycz /ID# 137654
Lodz, 93-509
Switzerland2 sites
Centre Hospitalier Univ Vaudoi /ID# 137929
Lausanne, 1011
University Hospital Zurich /ID# 137930
Zurich, 8091
Canada1 site
Montreal Neurological Institut /ID# 136309
Montreal, Quebec, H3A 2B4
Mexico1 site
Hospital Zambrano Hellion /ID# 138076
San Pedro Garza García, 66278
About this study
Official title: INTELLANCE-2: ABT-414 Alone or ABT-414 Plus Temozolomide Versus Lomustine or Temozolomide for Recurrent Glioblastoma: A Randomized Phase 2 Study of the EORTC Brain Tumor Group
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.
Read the detailed description
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.
- Conditions
- Glioblastoma
- Being tested
- Depatuxizumab mafodotin, Temozolomide, Lomustine
- Keywords
- Glioblastoma, Epithelial Growth Factor vIII mutation, Temozolomide, Lomustine, ABT-414, European Organization for Research and Treatment of Cancer, Recurrent glioblastoma, Epithelial Growth Factor, Brain Tumor, Brain Tumor Group, Antibody Drug Conjugate, EORTC, Pediatric High Grade Gliomas, Pediatric Diffuse Intrinsic Pontine Glioma, Pediatric WHO grade III glioma, Pediatric WHO grade IV glioma, EGFR amplification, Children
- Medical subject headings
- Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Depatuxizumab mafodotinDrug
Also called ABT-414
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).
TemozolomideDrug
Also called TMZ
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.
LomustineDrug
Also called Gleostine
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.
| Study group | Role | What they receive |
|---|---|---|
| ABT-414/temozolomide | Experimental | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants Receives: Drug: Depatuxizumab mafodotin; Drug: Temozolomide |
| ABT-414_adult | Experimental | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants Receives: Drug: Depatuxizumab mafodotin |
| Control_lomustine | Active comparator | 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. Receives: Drug: Lomustine |
| Control_ temozolomide | Active comparator | 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. Receives: Drug: Temozolomide |
| ABT-414_ pediatric | Experimental | 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). Receives: Drug: Depatuxizumab mafodotin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adult Study: Overall Survival (OS)
Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine).
Measured: From the date of randomization up to the date of participant's death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months.
Adult Study: Progression-Free Survival (PFS)
Progression-free survival was assessed per response assessment in neuro-oncology criteria (RANO) criteria and assessed by an independent review committee and was defined as the length of time during and after the treatment of a disease, that the participant lived with the disease but did not get worse.
Measured: Measured every 8 weeks from date of randomization until the date of first objective progression or subject's death, whichever occurred first, up to 2 years
Pediatric Study: Percentage of Participants With Adverse Events From the First Visit Until 49 Days After the Last Dose of Study Drug
The severity of each adverse event was rated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 4.0)
Measured: From participant's first visit until 49 days after the participant's last dose of study drug, up to 63 weeks
Pediatric Study: Maximum Observed Serum Concentration (Cmax) of ABT-414
Cmax is the peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Measured: Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose
Pediatric Study: Maximum Observed Plasma Concentration (Cmax) of Cys-mcMMAF
Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose. Cys-mcMMAF is a toxic metabolite of depatuxizumab mafodotin.
Measured: Samples collected Cycle 1 Days 1, 2, 3, 5, 8
Pediatric Study: Half-life (t1/2) Observed for ABT-414
Half-life is the calculated time it takes for half of the drug to leave the body.
Measured: Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose
Pediatric Study: Half-life (t1/2) Observed for Cys-mcMMAF
Half-life is the calculated time it takes for half of the drug or drug metabolite to leave the body. CysmcMMAF is a toxic metabolite of depatuxizumab mafodotin.
Measured: Samples collected Cycle 1 Days 1, 2, 3, 5, 8
Pediatric Study: Area Under the Concentration-time Curve (AUC) Observed for ABT-414
AUC is a measure of how long and how much drug is present in the body after dosing. The AUC of depatuxizumab mafodotin (ABT-414) in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population.
Measured: Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose
Pediatric Study: Area Under the Concentration-time-curve (AUC) Observed for Unconjugated Cys-mcMMAF
AUC is a measure of how long and how much drug or drug metabolite is present in the body after dosing. The AUC of Cys-mcMMAF, a toxic metabolite of depatuxizumab mafodotin, in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population.
Measured: Samples collected Cycle 1 Days 1, 2, 3, 5, 8
Secondary outcomes (9)
Adult Study: Objective Response Rate (ORR)
The objective response rate (ORR) included best overall responses - complete response (CR) and partial response (PR) - assessed by the independent review committee per response assessment in neurooncology criteria (RANO) criteria from the date of randomization until disease progression or death, whichever came first. All objective responses (CR and PR) must be have been confirmed by repeat MRI 4 weeks after the first time when CR or PR is identified. Any subject who did not meet CR or PR including those who did not have post-baseline radiological assessments was considered a nonresponder.
Measured: Every 8 weeks at each assessment of disease, up to 28 months
Adult Study: Overall Survival in the Subgroup With Epidermal Growth Factor Receptor (EGFRvIII) Mutation
Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine) for all randomized participants that had the Epidermal Growth Factor Receptor (EGFRvIII) mutation.
Measured: From the date of randomization up to the date of participant's death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months
Pediatric Study: Objective Response Rate (ORR)
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Measured: Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks
Pediatric Study: Best Tumor Response Rate
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Measured: Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks
Pediatric Study: Duration of Response
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Measured: Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks
Pediatric Study: Overall Survival
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Measured: From the date of enrollment to the date of death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months
Pediatric Study: Time to Progression
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/ temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, pediatric time to progression data analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Measured: Evaluated every 8 weeks (+/- 7 days) from the date of enrollment until the date of first objective progression or participant's death, whichever occurs first, up to approximately 52 weeks
Pediatric Study: Progression-Free Survival
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Measured: Evaluated every 8 weeks (+/- 7 days) from the date of enrollment until the date of first objective progression or participant's death, whichever occurs first, up to approximately 52 weeks
Pediatric Study: Percentage of Participants With Changes in Neurological Status and Functioning
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Measured: Baseline, Day 1 and 15 of each cycle, every 6 months for 5 years thereafter, and then annually
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2015 (estimated)
- Study start17 Feb 2015
- Primary completion24 Jun 2019
- Study completion24 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 266 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- AbbVie Inc., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02343406
- Sponsor's protocol ID
- M14-483
- Other IDs
- 2014-004438-24, EORTC 1410-BTG, 2014
- Acronym
- INTELLANCE-2
- Status last verified
- May 2020
- First submitted
- 22 Dec 2014
- Last updated
- 22 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Clement PMJ, Dirven L, Eoli M, Sepulveda-Sanchez JM, Walenkamp AME, Frenel JS, Franceschi E, Weller M, Chinot O, De Vos FYFL, Whenham N, Sanghera P, Looman J, Kundu MG, Peter de Geus J, Nuyens S, Spruyt M, Gorlia T, Coens C, Golfinopoulos V, Reijneveld JC, van den Bent MJ. Impact of depatuxizumab mafodotin on health-related quality of life and neurological functioning in the phase II EORTC 1410/INTELLANCE 2 trial for EGFR-amplified recurrent glioblastoma. Eur J Cancer. 2021 Apr;147:1-12. doi: 10.1016/j.ejca.2021.01.010. Epub 2021 Feb 15.
PubMed 33601293Van Den Bent M, Eoli M, Sepulveda JM, Smits M, Walenkamp A, Frenel JS, Franceschi E, Clement PM, Chinot O, De Vos F, Whenham N, Sanghera P, Weller M, Dubbink HJ, French P, Looman J, Dey J, Krause S, Ansell P, Nuyens S, Spruyt M, Brilhante J, Coens C, Gorlia T, Golfinopoulos V. INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma. Neuro Oncol. 2020 May 15;22(5):684-693. doi: 10.1093/neuonc/noz222.
PubMed 31747009Lassman AB, van den Bent MJ, Gan HK, Reardon DA, Kumthekar P, Butowski N, Lwin Z, Mikkelsen T, Nabors LB, Papadopoulos KP, Penas-Prado M, Simes J, Wheeler H, Walbert T, Scott AM, Gomez E, Lee HJ, Roberts-Rapp L, Xiong H, Ansell PJ, Bain E, Holen KD, Maag D, Merrell R. Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with EGFR-amplified, recurrent glioblastoma: results from an international phase I multicenter trial. Neuro Oncol. 2019 Jan 1;21(1):106-114. doi: 10.1093/neuonc/noy091.
PubMed 29982805Gan HK, Reardon DA, Lassman AB, Merrell R, van den Bent M, Butowski N, Lwin Z, Wheeler H, Fichtel L, Scott AM, Gomez EJ, Fischer J, Mandich H, Xiong H, Lee HJ, Munasinghe WP, Roberts-Rapp LA, Ansell PJ, Holen KD, Kumthekar P. Safety, pharmacokinetics, and antitumor response of depatuxizumab mafodotin as monotherapy or in combination with temozolomide in patients with glioblastoma. Neuro Oncol. 2018 May 18;20(6):838-847. doi: 10.1093/neuonc/nox202.
PubMed 29077941Reardon DA, Lassman AB, van den Bent M, Kumthekar P, Merrell R, Scott AM, Fichtel L, Sulman EP, Gomez E, Fischer J, Lee HJ, Munasinghe W, Xiong H, Mandich H, Roberts-Rapp L, Ansell P, Holen KD, Gan HK. Efficacy and safety results of ABT-414 in combination with radiation and temozolomide in newly diagnosed glioblastoma. Neuro Oncol. 2017 Jul 1;19(7):965-975. doi: 10.1093/neuonc/now257.
PubMed 28039367