Clinical Trials List
Protocol NumberM14-483
NCT Number(ClinicalTrials.gov Identfier)NCT02343406
2015-05-01 - 2020-06-11
Phase II
Terminated5
ICD-10C71
Malignant neoplasm of brain
ABT-414 alone or ABT-414 plus temozolomide versus lomustine or temozolomide for recurrent glioblastoma: a randomized phase II study of the EORTC Brain Tumor Group
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Trial Applicant
AbbVie
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Sponsor
AbbVie
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 陳信宏 Division of Pediatrics
- Yuan-Hung Wu Division of Radiology
- 許秉權 Division of Orthopedics
- 林士傑 Division of Others
- YI YEN LEE Division of Pediatrics
- 吳智君 Division of Radiology
- Min-Hsiung Chen Division of Orthopedics
- 張毓帆 Division of Ophthalmology
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chi-Cheng Chuang Division of Orthopedics
- 蔡宏杰 Division of Orthopedics
- Peng-Wei Hsu Division of Orthopedics
- Pin-Yuan Chen Division of Orthopedics
- 盧郁仁 Division of Orthopedics
- 黃盈誠 Division of Orthopedics
- Tang-Her Jaing Division of Orthopedics
The Actual Total Number of Participants Enrolled
4 Terminated
Audit
None
Co-Principal Investigator
- 黃佩欣 Division of Others
- SHIH-HUNG YANG Division of Orthopedics
- YA-FANG CHEN Division of Radiology
- YUNG-LI YANG Division of Pediatrics
- 曾漢民 Division of Orthopedics
- 郭夢菲 Division of Orthopedics
- SHIH-HUNG YANG Division of Orthopedics
- CHANG-PING LIN Division of Ophthalmology
- SHIANN-TANG JOU Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Glioblastoma Multiforme (GBM)
Objectives
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.
Test Drug
ABT-414
Active Ingredient
ABT-414
Dosage Form
Injection
Dosage
100 mg
20 mg
20 mg
Endpoints
The primary endpoint will be OS at final analysis and PFS according to
RANO criteria and assessed by IRC at the interim analysis.
Secondary endpoints will be:
♦ PFS according to RANO criteria and assessed by IRC and local
investigators
♦ Objective response rate (ORR)
♦ OS in the subgroup with EGFRvIII mutation
The following are exploratory endpoints:
♦ Best overall response rate (BOR), complete response rate (CRR),
duration of response (DR) assessed by IRC and local investigators will
be computed in each arm
♦ PFS in the subgroup with EGFRvIII mutation
♦ Neurological deterioration-free survival (NDFS)
♦ Frequencies and percentages of worst Adverse Events (AEs) or
Laboratory Event grades
♦ Quality of life
♦ Steroid use
RANO criteria and assessed by IRC at the interim analysis.
Secondary endpoints will be:
♦ PFS according to RANO criteria and assessed by IRC and local
investigators
♦ Objective response rate (ORR)
♦ OS in the subgroup with EGFRvIII mutation
The following are exploratory endpoints:
♦ Best overall response rate (BOR), complete response rate (CRR),
duration of response (DR) assessed by IRC and local investigators will
be computed in each arm
♦ PFS in the subgroup with EGFRvIII mutation
♦ Neurological deterioration-free survival (NDFS)
♦ Frequencies and percentages of worst Adverse Events (AEs) or
Laboratory Event grades
♦ Quality of life
♦ Steroid use
Inclution Criteria
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.
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.
Exclusion Criteria
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.
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.
The Estimated Number of Participants
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Taiwan
15 participants
-
Global
240 participants
