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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 (INTELLANCE 2)

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ClinicalTrials.gov Identifier: NCT02343406
Recruitment Status : Recruiting
First Posted : January 22, 2015
Last Update Posted : May 16, 2018
Sponsor:
Collaborator:
European Organisation for Research and Treatment of Cancer - EORTC
Information provided by (Responsible Party):
AbbVie

Brief Summary:

This study is to evaluate the efficacy and safety of ABT-414 alone or with temozolomide versus temozolomide or lomustine alone in participants with recurrent glioblastoma multiforme.

The study includes a Pediatric sub-study to evaluate safety, tolerability and pharmacokinetics of ABT-414 in a pediatric population.

Adult enrollment has been completed and the study is now only recruiting for pediatric participants.


Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Drug: Lomustine Drug: ABT-414 Drug: Temozolomide Phase 2

Detailed Description:
The pediatric sub-study is an uncontrolled, open-label, single-arm global study. This sub-study is to evaluate the safety, tolerability, and pharmacokinetics of ABT-414 in a pediatric population less than 18 years of age as well as to assess the effect of ABT-414 on tumor response per Response Assessment in Neuro-Oncology (RANO) criteria.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 260 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma: A Randomized Phase II Study of the EORTC Brain Tumor Group (EORTC Protocol 1410-BTG) Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas
Actual Study Start Date : February 11, 2015
Estimated Primary Completion Date : December 27, 2019
Estimated Study Completion Date : June 11, 2020


Arm Intervention/treatment
Experimental: Arm 4 Pediatric sub-study
ABT-414 at a dose of 1.0 mg/kg for participants who are 6 to 17 years old (at the date of first ABT-414 dose), or 1.3 mg/kg for participants who are 0 to 5 years old administered via intravenous infusion every other week. Prophylactic steroid eye drops (temozolomide) will be administered as described for the adult participants. Investigator discretion to use ABT-414 as monotherapy or in combination with temozolomide. The use of TMZ in combination with ABT-414 for a pediatric patient must be reviewed by the EORTC/AbbVie medical monitor prior to the initiation of therapy.
Drug: ABT-414
ABT-414 will be administered by intravenous infusion over approximately 30-40 minutes.
Other Names:
  • Depatuxizumab
  • Mafodotin

Experimental: Arm 2
ABT-414 administered every two weeks as monotherapy
Drug: ABT-414
ABT-414 will be administered by intravenous infusion over approximately 30-40 minutes.
Other Names:
  • Depatuxizumab
  • Mafodotin

Active Comparator: Arm 3A
Lomustine: For patients relapsing during TMZ treatment, or within 16 weeks after first day of last TMZ cycle: Lomustine will be administered on day 1 of every 42 day cycle.
Drug: Lomustine
Lomustine will be administered orally.

Drug: ABT-414
ABT-414 will be administered by intravenous infusion over approximately 30-40 minutes.
Other Names:
  • Depatuxizumab
  • Mafodotin

Experimental: Arm 1
ABT-414 administered via intravenous infusion every two weeks in combination with Temozolomide
Drug: ABT-414
ABT-414 will be administered by intravenous infusion over approximately 30-40 minutes.
Other Names:
  • Depatuxizumab
  • Mafodotin

Drug: Temozolomide
Temozolomide (TMZ) will be administered orally.

Active Comparator: Arm 3B
Temozolomide re-challenge: For patients that relapse 16 weeks or more after the first day of last dose of TMZ cycle: TMZ will be administered on day 1-5 of every 28 day cycle
Drug: ABT-414
ABT-414 will be administered by intravenous infusion over approximately 30-40 minutes.
Other Names:
  • Depatuxizumab
  • Mafodotin

Drug: Temozolomide
Temozolomide (TMZ) will be administered orally.




Primary Outcome Measures :
  1. Pediatric study: Maximum observed serum concentration (Cmax) for ABT-414 [ Time Frame: Samples collected at various time points from Cycle 1 Day 1 up to 35 days after the participant's last dose of study drug ]
    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.

  2. Adult study: Progression Free Survival (PFS) [ Time Frame: PFS will be measured every 8 weeks from date of randomization until the date of first objective progression or participant's death, whichever occurs first, up to 2 years. This will be assessed at interim analysis, when 45 PFS events are observed. ]
    Progression Free Survival per RANO criteria is the length of time during and after the treatment of a disease, that the participant lives with the disease but does not get worse.

  3. Pediatric study: AUC for Cys-mcMMAF (toxin, identified as a metabolite of ABT-414) [ Time Frame: Samples collected Cycle 1 Days 1, 2, 3, 5, 8 ]
    AUC is a measure of how long and how much drug or drug metabolite is present in the body after dosing. AUC in pediatric population will be compared following treatment, to check that this is comparable to adults, and the dosing levels are appropriate for a pediatric population.

  4. Pediatric study: Half-life (t1/2) observed for ABT-414 [ Time Frame: Samples collected at various time points from Cycle 1 Day 1 up to 35 days after the participant's last dose of study drug. ]
    Half-life is the calculated time it takes for half of the drug to leave the body.

  5. Pediatric study: Area Under the Concentration-time Curve (AUC) observed for ABT-414 [ Time Frame: Samples collected at various time points from Cycle 1 Day 1 up to 35 days after the participant's last dose of study drug. ]
    AUC is a measure of how long and how much drug is present in the body after dosing. AUC in pediatric population will be compared following treatment, to check that this is comparable to adults, and the dosing levels are appropriate for a pediatric population.

  6. Pediatric study: Maximum observed plasma concentration (Cmax) for Cys-mcMMAF (toxin, identified as a metabolite of ABT-414) [ Time Frame: Samples collected Cycle 1 Days 1, 2, 3, 5, 8 ]
    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.

  7. Pediatric study: t1/2 for Cys-mcMMAF (toxin, identified as a metabolite of ABT-414) [ Time Frame: Samples collected Cycle 1 Days 1, 2, 3, 5, 8 ]
    Half-life is the calculated time it takes for half of the drug or drug metabolite to leave the body.

  8. Adult study: Overall Survival (OS) [ Time Frame: Measured from the date of randomization up to the date of participant's death. Participants who complete treatment will be assessed every 12 weeks, up to 28 months. ]
    Overall Survival (OS) is defined as number of days from the date of randomization to the date of death for all dosed participants.

  9. Pediatric study: Safety including toxicities according to CTCAE criteria [ Time Frame: From participants first visit until 35 days after the participant's last dose of study drug ]
    The severity of each adverse event is rated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 4.0)


Secondary Outcome Measures :
  1. Pediatric study: Objective response rate, best response rate and duration of response based on RANO criteria [ Time Frame: Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to RANO criteria, until progression or withdrawal up to approximately 52 weeks. ]
    Objective response includes best overall responses (complete response and partial response)

  2. Pediatric study: Overall survival, Time to progression and Time to progression-free survival [ Time Frame: Time to progression and time to progression-free survival will be measured every 8 weeks (+/- 7 days) from date of enrollment until the date of first objective progression or participant's death, whichever occurs first, upto approximately 52 weeks ]
    Overall survival is defined as number of days from the date of enrollment to the date of death for all dosed participation. Progression Free Survival per RANO criteria is the length of time during and after the treatment of a disease, that the participant lives with the disease but does not progress.

  3. Adult study: Overall Response Rate (ORR) [ Time Frame: The overall response rate will be evaluated every 8 weeks at each assessment of disease according to RANO criteria, up to 28 months. ]
    Overall Response Rate will look at those complete responders and partial responders

  4. Pediatric study: Changes in neurological status and function (including PedsQL cancer module) [ Time Frame: Neurological status and functioning is assessed at baseline, day 1 and 15 of each cycle, every 6 months for 5 years thereafter and then annually PedsQL evaluated at baseline, week 16 on treatment and at 6 months. ]
    The Pediatric Quality of Life Inventory (PedsQL) is a modular instrument designed to measure health-related quality of life (HRQOL) in children and adolescents ages 2-18 years. Neurological status and functioning will be assessed also at physical examination during the study

  5. Adult study: Progression Free Survival (PFS) [ Time Frame: Progression Free Survival will be measured every 8 weeks from date of randomization until the date of first objective progression or date of participant's death, whichever occurs first, assessed up to 28 months. ]
    Progression Free Survival per RANO criteria is the length of time during and after the treatment of a disease, that the participant lives with the disease but does not get worse.

  6. Adult study: Overall Survival in the subgroup with Epithelial Growth Factor Receptor (EGFRvIII) mutation [ Time Frame: Measured from date of randomization until death, or lost to follow up, assessed up to 28 months. ]
    Overall Survival (OS) is defined as number of days from the date of randomization to the date of death for all randomized participants that have EGFR vIII mutation.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   up to 99 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Adult participants (greater than or equal to 18 years old):

  • Histologically confirmed de novo (primary) Glioblastoma Multiforme 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.

Pediatric sub-study participants (less than 18 years old):

  • The study will only include patients under 3 years of age when results of a juvenile repeated mouse toxicity study become available and are favorable to support use in patients aged under 3 years.
  • 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.

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, 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 65Gy 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02343406


Contacts
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

  Show 99 Study Locations
Sponsors and Collaborators
AbbVie
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Director: AbbVie Inc. AbbVie

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02343406     History of Changes
Other Study ID Numbers: M14-483
2014-004438-24 ( EudraCT Number )
EORTC 1410-BTG ( Other Grant/Funding Number: European Organization for Research and Treatment of Cancer (EORTC) )
First Posted: January 22, 2015    Key Record Dates
Last Update Posted: May 16, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by AbbVie:
Glioblastoma Multiforme
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

Additional relevant MeSH terms:
Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Lomustine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents