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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02343406




Registration number
NCT02343406
Ethics application status
Date submitted
22/12/2014
Date registered
22/01/2015

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2014-004438-24
Secondary ID [2] 0 0
M14-483
Universal Trial Number (UTN)
Trial acronym
INTELLANCE-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Depatuxizumab mafodotin
Treatment: Drugs - Temozolomide
Treatment: Drugs - Lomustine

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).


Treatment: Drugs: 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).

Treatment: Drugs: 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.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adult Study: Overall Survival (OS)
Timepoint [1] 0 0
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.
Primary outcome [2] 0 0
Adult Study: Progression-Free Survival (PFS)
Timepoint [2] 0 0
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
Primary outcome [3] 0 0
Pediatric Study: Percentage of Participants With Adverse Events From the First Visit Until 49 Days After the Last Dose of Study Drug
Timepoint [3] 0 0
From participant's first visit until 49 days after the participant's last dose of study drug, up to 63 weeks
Primary outcome [4] 0 0
Pediatric Study: Maximum Observed Serum Concentration (Cmax) of ABT-414
Timepoint [4] 0 0
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
Primary outcome [5] 0 0
Pediatric Study: Maximum Observed Plasma Concentration (Cmax) of Cys-mcMMAF
Timepoint [5] 0 0
Samples collected Cycle 1 Days 1, 2, 3, 5, 8
Primary outcome [6] 0 0
Pediatric Study: Half-life (t1/2) Observed for ABT-414
Timepoint [6] 0 0
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
Primary outcome [7] 0 0
Pediatric Study: Half-life (t1/2) Observed for Cys-mcMMAF
Timepoint [7] 0 0
Samples collected Cycle 1 Days 1, 2, 3, 5, 8
Primary outcome [8] 0 0
Pediatric Study: Area Under the Concentration-time Curve (AUC) Observed for ABT-414
Timepoint [8] 0 0
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
Primary outcome [9] 0 0
Pediatric Study: Area Under the Concentration-time-curve (AUC) Observed for Unconjugated Cys-mcMMAF
Timepoint [9] 0 0
Samples collected Cycle 1 Days 1, 2, 3, 5, 8
Secondary outcome [1] 0 0
Adult Study: Objective Response Rate (ORR)
Timepoint [1] 0 0
Every 8 weeks at each assessment of disease, up to 28 months
Secondary outcome [2] 0 0
Adult Study: Overall Survival in the Subgroup With Epidermal Growth Factor Receptor (EGFRvIII) Mutation
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Pediatric Study: Objective Response Rate (ORR)
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Pediatric Study: Best Tumor Response Rate
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Pediatric Study: Duration of Response
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
Pediatric Study: Overall Survival
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
Pediatric Study: Time to Progression
Timepoint [7] 0 0
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
Secondary outcome [8] 0 0
Pediatric Study: Progression-Free Survival
Timepoint [8] 0 0
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
Secondary outcome [9] 0 0
Pediatric Study: Percentage of Participants With Changes in Neurological Status and Functioning
Timepoint [9] 0 0
Baseline, Day 1 and 15 of each cycle, every 6 months for 5 years thereafter, and then annually

Eligibility
Key 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). 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.
Minimum age
No limit
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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). 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/02/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/06/2019
Sample size
Target
Accrual to date
Final
266
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC
Recruitment hospital [1] 0 0
Port Macquarie Base Hospital /ID# 134569 - Port Macquarie
Recruitment hospital [2] 0 0
Sydney Children's Hospital /ID# 153533 - Randwick
Recruitment hospital [3] 0 0
Royal North Shore Hospital /ID# 147092 - Saint Leonards
Recruitment hospital [4] 0 0
Calvary Mater Newcastle /ID# 134570 - Waratah
Recruitment hospital [5] 0 0
Southern Medical Day Care Ctr /ID# 134495 - Wollongong
Recruitment hospital [6] 0 0
Royal Brisbane and Women's Hospital /ID# 147091 - Herston
Recruitment hospital [7] 0 0
Royal Adelaide Hospital /ID# 135208 - Adelaide
Recruitment hospital [8] 0 0
Royal Hobart Hospital /ID# 135209 - Hobart
Recruitment hospital [9] 0 0
Barwon Health University Hospital Geelong /ID# 134493 - Geelong
Recruitment hospital [10] 0 0
Royal Children's Hospital /ID# 157624 - Melbourne
Recruitment postcode(s) [1] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [4] 0 0
2298 - Waratah
Recruitment postcode(s) [5] 0 0
2500 - Wollongong
Recruitment postcode(s) [6] 0 0
4029 - Herston
Recruitment postcode(s) [7] 0 0
5000 - Adelaide
Recruitment postcode(s) [8] 0 0
7000 - Hobart
Recruitment postcode(s) [9] 0 0
3220 - Geelong
Recruitment postcode(s) [10] 0 0
3052 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Austria
State/province [11] 0 0
Niederoesterreich
Country [12] 0 0
Austria
State/province [12] 0 0
Graz
Country [13] 0 0
Austria
State/province [13] 0 0
Linz
Country [14] 0 0
Belgium
State/province [14] 0 0
Bruxelles-Capitale
Country [15] 0 0
Belgium
State/province [15] 0 0
Hainaut
Country [16] 0 0
Belgium
State/province [16] 0 0
Oost-Vlaanderen
Country [17] 0 0
Belgium
State/province [17] 0 0
West-Vlaanderen
Country [18] 0 0
Belgium
State/province [18] 0 0
Antwerp
Country [19] 0 0
Belgium
State/province [19] 0 0
Leuven
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
Czechia
State/province [21] 0 0
Praha 5
Country [22] 0 0
Czechia
State/province [22] 0 0
Brno
Country [23] 0 0
Czechia
State/province [23] 0 0
Hradec Kralove
Country [24] 0 0
Czechia
State/province [24] 0 0
Ostrava
Country [25] 0 0
Finland
State/province [25] 0 0
Helsinki
Country [26] 0 0
Finland
State/province [26] 0 0
Turku
Country [27] 0 0
France
State/province [27] 0 0
Hauts-de-France
Country [28] 0 0
France
State/province [28] 0 0
Ile-de-France
Country [29] 0 0
France
State/province [29] 0 0
Loire-Atlantique
Country [30] 0 0
France
State/province [30] 0 0
Provence-Alpes-Cote-d Azur
Country [31] 0 0
France
State/province [31] 0 0
Rhone
Country [32] 0 0
France
State/province [32] 0 0
Angers
Country [33] 0 0
France
State/province [33] 0 0
Bron
Country [34] 0 0
France
State/province [34] 0 0
Paris
Country [35] 0 0
Germany
State/province [35] 0 0
Baden-Wuerttemberg
Country [36] 0 0
Germany
State/province [36] 0 0
Bayern
Country [37] 0 0
Germany
State/province [37] 0 0
Hamburg
Country [38] 0 0
Germany
State/province [38] 0 0
Munich
Country [39] 0 0
Germany
State/province [39] 0 0
Tuebingen
Country [40] 0 0
Hungary
State/province [40] 0 0
Pecs
Country [41] 0 0
Hungary
State/province [41] 0 0
Budapest
Country [42] 0 0
Hungary
State/province [42] 0 0
Debrecen
Country [43] 0 0
Ireland
State/province [43] 0 0
Cork
Country [44] 0 0
Ireland
State/province [44] 0 0
Dublin
Country [45] 0 0
Italy
State/province [45] 0 0
Bologna
Country [46] 0 0
Italy
State/province [46] 0 0
Bolzano
Country [47] 0 0
Italy
State/province [47] 0 0
Milan
Country [48] 0 0
Italy
State/province [48] 0 0
Padova
Country [49] 0 0
Italy
State/province [49] 0 0
Rome
Country [50] 0 0
Korea, Republic of
State/province [50] 0 0
Gyeonggido
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Seoul Teugbyeolsi
Country [52] 0 0
Korea, Republic of
State/province [52] 0 0
Seoul
Country [53] 0 0
Mexico
State/province [53] 0 0
San Pedro Garza García
Country [54] 0 0
Netherlands
State/province [54] 0 0
Amsterdam
Country [55] 0 0
Netherlands
State/province [55] 0 0
Groningen
Country [56] 0 0
Netherlands
State/province [56] 0 0
Rotterdam
Country [57] 0 0
Netherlands
State/province [57] 0 0
The Hague
Country [58] 0 0
Netherlands
State/province [58] 0 0
Utrecht
Country [59] 0 0
Poland
State/province [59] 0 0
Mazowieckie
Country [60] 0 0
Poland
State/province [60] 0 0
Lodz
Country [61] 0 0
Singapore
State/province [61] 0 0
Singapore
Country [62] 0 0
Spain
State/province [62] 0 0
Barcelona
Country [63] 0 0
Spain
State/province [63] 0 0
Navarra, Comunidad
Country [64] 0 0
Spain
State/province [64] 0 0
Madrid
Country [65] 0 0
Switzerland
State/province [65] 0 0
Lausanne
Country [66] 0 0
Switzerland
State/province [66] 0 0
Zurich
Country [67] 0 0
Taiwan
State/province [67] 0 0
Taichung
Country [68] 0 0
Taiwan
State/province [68] 0 0
Taipei
Country [69] 0 0
Taiwan
State/province [69] 0 0
Taichung City
Country [70] 0 0
Taiwan
State/province [70] 0 0
Taipei City
Country [71] 0 0
Taiwan
State/province [71] 0 0
Taoyuan City
Country [72] 0 0
United Kingdom
State/province [72] 0 0
London, City Of
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Birmingham
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Glasgow
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Hull
Country [76] 0 0
United Kingdom
State/province [76] 0 0
London
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
European Organisation for Research and Treatment of Cancer - EORTC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR), Analytic code
When will data be available (start and end dates)?
Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Available to whom?
Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02343406