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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)

NCT02343406

Description:

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.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

ABT-414 Alone or ABT-414 Plus <span class="go-doc-concept go-doc-intervention">Temozolomide</span> vs. <span class="go-doc-concept go-doc-intervention">Lomustine</span> or <span class="go-doc-concept go-doc-intervention">Temozolomide</span> for Recurrent <span class="go-doc-concept go-doc-disease">Glioblastoma</span>

Title

  • Brief Title: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma
  • Official Title: 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)
  • Clinical Trial IDs

    NCT ID: NCT02343406

    ORG ID: M14-483

    NCI ID: 2014-004438-24

    Trial Conditions

    Glioblastoma Multiforme

    Trial Interventions

    Drug Synonyms Arms
    ABT-414 Arm 1, Arm 2
    Lomustine Arm 3A
    Temozolomide Arm 1, Arm 3B

    Trial Purpose

    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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Arm 1 Experimental ABT-414 administered via intravenous infusion every two weeks in combination with Temozolomide ABT-414, Temozolomide
    Arm 2 Experimental ABT-414 administered every two weeks as monotherapy ABT-414
    Arm 3A Active Comparator 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. Lomustine
    Arm 3B Active Comparator 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 Temozolomide

    Eligibility Criteria

    Inclusion Criteria:

    1. 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

    2. 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.

    3. Availability of adequate biological material (formalin-fixed paraffin embedded [FFPE]
    tumor) for central testing of Epithelial Growth Factor Receptor (EGFR) amplification

    4. Presence of EGFR amplification confirmed by central assessment; patients with
    undetermined EGFR status are excluded

    5. World Health Organization (WHO) Performance status 0 - 2

    6. 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.

    7. Post surgery MRI within 48 hours following surgery, however an MRI scan has to be
    done within 2 weeks prior to randomization.

    8. Surgery completed at least 2 weeks before randomization and patients should have
    fully recovered as assessed by investigators.

    Exclusion Criteria:

    1. Prior treatment with nitrosoureas

    2. Prior treatment with bevacizumab

    3. Previous exposure to Epithelial Growth Factor Receptor (EGFR) targeted agents,
    including EGFRvIII targeting agents

    4. Prior discontinuation of temozolomide chemotherapy for toxicity reasons

    5. Prior Radiation Therapy (RT) with a dose over 65 Gy, stereotactic radiosurgery or
    brachytherapy unless the recurrence is histologically proven

    6. 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

    7. 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.

    8. No history of wheat allergies and Coeliac disease.

    9. 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 99 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Overall Survival (OS)

    Progression Free Survival (PFS)

    Secondary Outcome Measures

    Progression Free Survival (PFS)

    Overall Response Rate (ORR)

    Overall Survival in the subgroup with Epithelial Growth Factor Receptor (EGFRvIII) mutation

    Trial Keywords

    European Organization for Research and Treatment of Cancer

    Epithelial Growth Factor

    Brain Tumor Group

    Lomustine

    ABT-414

    EORTC

    Glioblastoma Multiforme

    Epithelial Growth Factor vIII mutation

    Antibody Drug Conjugate

    Brain Tumor

    Temozolomide

    recurrent glioblastoma