Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02573324




Registration number
NCT02573324
Ethics application status
Date submitted
28/09/2015
Date registered
9/10/2015
Date last updated
11/05/2023

Titles & IDs
Public title
A Study of ABT-414 in Participants With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification
Scientific title
A Randomized, Placebo Controlled Phase 3 Study of ABT-414 With Concurrent Chemoradiation and Adjuvant Temozolomide in Subjects With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification (Intellance1)
Secondary ID [1] 0 0
2015-001166-26
Secondary ID [2] 0 0
M13-813
Universal Trial Number (UTN)
Trial acronym
Intellance1
Linked study record

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

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Temozolomide
Treatment: Drugs - Depatuxizumab mafodotin
Treatment: Drugs - Placebo for ABT-414

Experimental: Depatuxizumab Mafodotin, Radiation and Temozolomide (TMZ) - Depatuxizumab mafodotin is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase.

Placebo comparator: Placebo, Radiation and TMZ - Placebo is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Placebo is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase.

Experimental: Open-Label Sub-Study: Depatuxizumab Mafodotin, Radiation and TMZ - Depatuxizumab mafodotin is given to participants with hepatic impairment on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase.


Treatment: Drugs: Temozolomide
Oral Capsule

Treatment: Drugs: Depatuxizumab mafodotin
Intravenous (IV) Infusion

Treatment: Drugs: Placebo for ABT-414
IV Infusion (IV)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).
Secondary outcome [1] 0 0
OS for the O6-methylguaninemethlytransferese (MGMT) Unmethylated Group
Timepoint [1] 0 0
Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).
Secondary outcome [2] 0 0
OS for the MGMT Methylated Group
Timepoint [2] 0 0
Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).
Secondary outcome [3] 0 0
OS for the Epidermal Growth Factor Receptor (EGFR)vIII-Mutated Tumor Subgroup
Timepoint [3] 0 0
Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).
Secondary outcome [4] 0 0
Progression-Free Survival (PFS)
Timepoint [4] 0 0
Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).
Secondary outcome [5] 0 0
PFS for EGFRvIII-Mutated Tumor Subgroup
Timepoint [5] 0 0
Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).
Secondary outcome [6] 0 0
Deterioration Free Survival in M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) Symptom Severity Score
Timepoint [6] 0 0
Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).
Secondary outcome [7] 0 0
Deterioration Free Survival in MDASI-BT Symptom Interference Score
Timepoint [7] 0 0
Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).
Secondary outcome [8] 0 0
Deterioration Free Survival in Neurocognitive Functioning on the Hopkins Verbal Learning Test Revised (HVLT-R) Total Recall Score
Timepoint [8] 0 0
Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).

Eligibility
Key inclusion criteria
* Must have a clinical diagnosis of glioblastoma (GBM).
* Must have a confirmed epidermal growth factor receptor amplification in tumor tissue.
* Must have a Karnofsky Performance Status (KPS) >= 70 at assessment <= 14 days prior to randomization (N/A to the sub-study).
* Must have recovered from effects of surgery, postoperative infection and other complications of surgery.
* Must have adequate bone marrow, renal, and hepatic function (For the sub-study, the participant must have adequate bone marrow and renal function and have mild-to-moderate hepatic impairment).
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Multifocal, recurrent or metastatic GBM or gliomatosis cerebri (For the sub-study, the participant can have multifocal GBM and glimatosis cerebri but can't have recurrent or metastatic GBM).
* Prior chemo therapy or radiosensitizer for head and neck cancer.
* Prior radiotherapy to the head or neck in overlap of radiation fields.
* Prior therapy for glioblastoma or other invasive malignancy.
* Prior, concomitant or planned treatment with Novo Tumor Treatment Fields (Novo-TTF), EGFR-targeted therapy, bevacizumab, Gliadel wafers or other intratumoral or intracavity anti-neoplastic therapy.

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
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
4/01/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/04/2022
Sample size
Target
Accrual to date
Final
691
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Liverpool Hospital /ID# 144392 - Liverpool
Recruitment hospital [2] 0 0
Duplicate_The Prince of Wales Hospital /ID# 144882 - Randwick
Recruitment hospital [3] 0 0
Royal North Shore Hospital /ID# 143870 - St Leonards
Recruitment hospital [4] 0 0
Calvary Mater Newcastle /ID# 143860 - Waratah
Recruitment hospital [5] 0 0
Southern Medical Day Care Centre /ID# 143868 - Wollongong
Recruitment hospital [6] 0 0
Princess Alexandra Hospital /ID# 143857 - Woolloongabba
Recruitment hospital [7] 0 0
Royal Adelaide Hospital /ID# 143867 - Adelaide
Recruitment hospital [8] 0 0
Calvary North Adelaide Hospita /ID# 143866 - Adelaide
Recruitment hospital [9] 0 0
St Vincent's Hospital Melbourne /ID# 143858 - Fitzroy Melbourne
Recruitment hospital [10] 0 0
Duplicate_Austin Hospital /ID# 143859 - Heidelberg
Recruitment hospital [11] 0 0
St John Of God Subiaco Hospital /ID# 143869 - Subiaco
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment postcode(s) [4] 0 0
2298 - Waratah
Recruitment postcode(s) [5] 0 0
2500 - Wollongong
Recruitment postcode(s) [6] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [7] 0 0
5000 - Adelaide
Recruitment postcode(s) [8] 0 0
5006 - Adelaide
Recruitment postcode(s) [9] 0 0
3065 - Fitzroy Melbourne
Recruitment postcode(s) [10] 0 0
3084 - Heidelberg
Recruitment postcode(s) [11] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Delaware
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Indiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Kansas
Country [12] 0 0
United States of America
State/province [12] 0 0
Maine
Country [13] 0 0
United States of America
State/province [13] 0 0
Massachusetts
Country [14] 0 0
United States of America
State/province [14] 0 0
Michigan
Country [15] 0 0
United States of America
State/province [15] 0 0
Minnesota
Country [16] 0 0
United States of America
State/province [16] 0 0
Missouri
Country [17] 0 0
United States of America
State/province [17] 0 0
Nebraska
Country [18] 0 0
United States of America
State/province [18] 0 0
New Jersey
Country [19] 0 0
United States of America
State/province [19] 0 0
New York
Country [20] 0 0
United States of America
State/province [20] 0 0
North Carolina
Country [21] 0 0
United States of America
State/province [21] 0 0
Ohio
Country [22] 0 0
United States of America
State/province [22] 0 0
Oklahoma
Country [23] 0 0
United States of America
State/province [23] 0 0
Pennsylvania
Country [24] 0 0
United States of America
State/province [24] 0 0
South Carolina
Country [25] 0 0
United States of America
State/province [25] 0 0
Texas
Country [26] 0 0
United States of America
State/province [26] 0 0
Utah
Country [27] 0 0
United States of America
State/province [27] 0 0
Virginia
Country [28] 0 0
United States of America
State/province [28] 0 0
Washington
Country [29] 0 0
United States of America
State/province [29] 0 0
Wisconsin
Country [30] 0 0
Argentina
State/province [30] 0 0
Santa Fe
Country [31] 0 0
Argentina
State/province [31] 0 0
Buenos Aires
Country [32] 0 0
Austria
State/province [32] 0 0
Steiermark
Country [33] 0 0
Austria
State/province [33] 0 0
Wien
Country [34] 0 0
Austria
State/province [34] 0 0
Innsbruck
Country [35] 0 0
Austria
State/province [35] 0 0
Linz
Country [36] 0 0
Belgium
State/province [36] 0 0
Bruxelles-Capitale
Country [37] 0 0
Belgium
State/province [37] 0 0
Hainaut
Country [38] 0 0
Belgium
State/province [38] 0 0
Oost-Vlaanderen
Country [39] 0 0
Belgium
State/province [39] 0 0
Vlaams-Brabant
Country [40] 0 0
Belgium
State/province [40] 0 0
La Louvière
Country [41] 0 0
Belgium
State/province [41] 0 0
Liege
Country [42] 0 0
Belgium
State/province [42] 0 0
Yvoir
Country [43] 0 0
Brazil
State/province [43] 0 0
Rio Grande Do Norte
Country [44] 0 0
Brazil
State/province [44] 0 0
Rio Grande Do Sul
Country [45] 0 0
Brazil
State/province [45] 0 0
Sao Paulo
Country [46] 0 0
Brazil
State/province [46] 0 0
Rio de Janeiro
Country [47] 0 0
Canada
State/province [47] 0 0
Manitoba
Country [48] 0 0
Canada
State/province [48] 0 0
Nova Scotia
Country [49] 0 0
Canada
State/province [49] 0 0
Ontario
Country [50] 0 0
Canada
State/province [50] 0 0
Quebec
Country [51] 0 0
China
State/province [51] 0 0
Anhui
Country [52] 0 0
China
State/province [52] 0 0
Beijing
Country [53] 0 0
China
State/province [53] 0 0
Guangdong
Country [54] 0 0
China
State/province [54] 0 0
Hubei
Country [55] 0 0
China
State/province [55] 0 0
Hunan
Country [56] 0 0
China
State/province [56] 0 0
Jiangsu
Country [57] 0 0
China
State/province [57] 0 0
Shaanxi
Country [58] 0 0
China
State/province [58] 0 0
Shanghai
Country [59] 0 0
China
State/province [59] 0 0
Zhejiang
Country [60] 0 0
China
State/province [60] 0 0
Fuzhou
Country [61] 0 0
China
State/province [61] 0 0
Shenyang
Country [62] 0 0
China
State/province [62] 0 0
Tianjin
Country [63] 0 0
Colombia
State/province [63] 0 0
Antioquia
Country [64] 0 0
Colombia
State/province [64] 0 0
Cordoba
Country [65] 0 0
Colombia
State/province [65] 0 0
Cundinamarca
Country [66] 0 0
Colombia
State/province [66] 0 0
Risaralda
Country [67] 0 0
Colombia
State/province [67] 0 0
Cali
Country [68] 0 0
Czechia
State/province [68] 0 0
Brno
Country [69] 0 0
Czechia
State/province [69] 0 0
Hradec Kralove
Country [70] 0 0
Czechia
State/province [70] 0 0
Liberec
Country [71] 0 0
Czechia
State/province [71] 0 0
Ostrava
Country [72] 0 0
Czechia
State/province [72] 0 0
Praha
Country [73] 0 0
France
State/province [73] 0 0
Bouches-du-Rhone
Country [74] 0 0
France
State/province [74] 0 0
Hauts-de-France
Country [75] 0 0
France
State/province [75] 0 0
Ile-de-France
Country [76] 0 0
France
State/province [76] 0 0
Loire-Atlantique
Country [77] 0 0
France
State/province [77] 0 0
Provence-Alpes-Cote-d Azur
Country [78] 0 0
France
State/province [78] 0 0
Angers
Country [79] 0 0
France
State/province [79] 0 0
Paris
Country [80] 0 0
Germany
State/province [80] 0 0
Baden-Wuerttemberg
Country [81] 0 0
Germany
State/province [81] 0 0
Sachsen
Country [82] 0 0
Germany
State/province [82] 0 0
Bochum
Country [83] 0 0
Hong Kong
State/province [83] 0 0
Hong Kong
Country [84] 0 0
Ireland
State/province [84] 0 0
Dublin
Country [85] 0 0
Israel
State/province [85] 0 0
Tel-Aviv
Country [86] 0 0
Israel
State/province [86] 0 0
Haifa
Country [87] 0 0
Israel
State/province [87] 0 0
Jerusalem
Country [88] 0 0
Israel
State/province [88] 0 0
Petakh Tikva
Country [89] 0 0
Italy
State/province [89] 0 0
Piemonte
Country [90] 0 0
Italy
State/province [90] 0 0
Milan
Country [91] 0 0
Italy
State/province [91] 0 0
Padova
Country [92] 0 0
Italy
State/province [92] 0 0
Rome
Country [93] 0 0
Korea, Republic of
State/province [93] 0 0
Gyeonggido
Country [94] 0 0
Korea, Republic of
State/province [94] 0 0
Seoul Teugbyeolsi
Country [95] 0 0
Korea, Republic of
State/province [95] 0 0
Seoul
Country [96] 0 0
Mexico
State/province [96] 0 0
Nuevo Leon
Country [97] 0 0
Netherlands
State/province [97] 0 0
Amsterdam
Country [98] 0 0
Netherlands
State/province [98] 0 0
Den Haag
Country [99] 0 0
Netherlands
State/province [99] 0 0
Groningen
Country [100] 0 0
Netherlands
State/province [100] 0 0
Maastricht
Country [101] 0 0
Netherlands
State/province [101] 0 0
Utrecht
Country [102] 0 0
New Zealand
State/province [102] 0 0
Christchurch
Country [103] 0 0
New Zealand
State/province [103] 0 0
Wellington
Country [104] 0 0
Portugal
State/province [104] 0 0
Braga
Country [105] 0 0
Portugal
State/province [105] 0 0
Faro
Country [106] 0 0
Portugal
State/province [106] 0 0
Lisboa
Country [107] 0 0
Portugal
State/province [107] 0 0
Porto
Country [108] 0 0
Russian Federation
State/province [108] 0 0
Kaliningradskaya Oblast
Country [109] 0 0
Russian Federation
State/province [109] 0 0
Kirovskaya Oblast
Country [110] 0 0
Russian Federation
State/province [110] 0 0
Moskovskaya Oblast
Country [111] 0 0
Russian Federation
State/province [111] 0 0
Moskva
Country [112] 0 0
Russian Federation
State/province [112] 0 0
Sverdlovskaya Oblast
Country [113] 0 0
Singapore
State/province [113] 0 0
Singapore
Country [114] 0 0
South Africa
State/province [114] 0 0
Free State
Country [115] 0 0
South Africa
State/province [115] 0 0
Gauteng
Country [116] 0 0
South Africa
State/province [116] 0 0
Kwazulu-Natal
Country [117] 0 0
South Africa
State/province [117] 0 0
Western Cape
Country [118] 0 0
Spain
State/province [118] 0 0
Malaga
Country [119] 0 0
Spain
State/province [119] 0 0
Barcelona
Country [120] 0 0
Spain
State/province [120] 0 0
Madrid
Country [121] 0 0
Spain
State/province [121] 0 0
Valencia
Country [122] 0 0
Switzerland
State/province [122] 0 0
Aargau
Country [123] 0 0
Switzerland
State/province [123] 0 0
Zuerich
Country [124] 0 0
Switzerland
State/province [124] 0 0
Bellinzona
Country [125] 0 0
Switzerland
State/province [125] 0 0
Bern
Country [126] 0 0
Taiwan
State/province [126] 0 0
Taipei City
Country [127] 0 0
Taiwan
State/province [127] 0 0
Taoyuan City
Country [128] 0 0
United Kingdom
State/province [128] 0 0
London, City Of
Country [129] 0 0
United Kingdom
State/province [129] 0 0
Birmingham
Country [130] 0 0
United Kingdom
State/province [130] 0 0
Cardiff
Country [131] 0 0
United Kingdom
State/province [131] 0 0
Dundee
Country [132] 0 0
United Kingdom
State/province [132] 0 0
Edinburgh
Country [133] 0 0
United Kingdom
State/province [133] 0 0
Leeds
Country [134] 0 0
United Kingdom
State/province [134] 0 0
London
Country [135] 0 0
United Kingdom
State/province [135] 0 0
Newcastle Upon Tyne
Country [136] 0 0
United Kingdom
State/province [136] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Radiation Therapy Oncology Group
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study seeks to determine whether the addition of ABT-414 to concomitant radiotherapy and temozolomide (TMZ) followed by combination of ABT-414 with adjuvant TMZ prolongs overall survival (OS) among participants with newly diagnosed glioblastoma (GBM) with epidermal growth factor receptor (EGFR) amplification.

In addition, there is a Phase 1, open-label, multicenter sub-study to assess the pharmacokinetics, safety and tolerability of ABT-414 in participants with newly diagnosed EGFR-amplified GBM who have mild or moderate hepatic impairment.
Trial website
https://clinicaltrials.gov/study/NCT02573324
Trial related presentations / publications
Lassman 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.
Gan 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.
Reardon 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.
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02573324