AMG 595 First-in-Human in Recurrent Gliomas

This study is currently recruiting participants.
Verified February 2014 by Amgen
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01475006
First received: September 29, 2011
Last updated: February 4, 2014
Last verified: February 2014

September 29, 2011
February 4, 2014
November 2011
June 2015   (final data collection date for primary outcome measure)
  • Clinically significant or > or = to Grade 3 CTCAE changes in safety laboratory tests, physical exams, ECGs or vital signs [ Time Frame: 28 Days after last subject enrolled of each cohort in Part 1 and every 10, 20 and 30 subject enrolled in part 2 (if available) ] [ Designated as safety issue: Yes ]
  • PK Parameters: Cmax, Cmin, and if feasible half life - 8 time points up to 6 weeks [ Time Frame: 28 Days after last subject enrolled of each cohort in Part 1 and every 10, 20 and 30 subject enrolled in part 2 (if available) ] [ Designated as safety issue: Yes ]
  • Objective response in GBM tumors as assessed by Macdonald criteria [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Dose limiting toxicity used to estimate the MTD [ Time Frame: 28 Days after last subject enrolled of each cohort in Part 1 and every 10, 20 and 30 subject enrolled in part 2 (if available) ] [ Designated as safety issue: Yes ]
  • Clinically significant or > or = to Grade 3 CTCAE changes in safety laboratory tests, physical exams, ECGs or vitals signs [ Time Frame: 28 Days after last subject enrolled of each cohort in Part 1 and every 10, 20 and 30 subject enrolled in part 2 (if available) ] [ Designated as safety issue: Yes ]
  • PK Parameters: Cmax, Cmin, and if feasible half life [ Time Frame: 28 Days after last subject enrolled of each cohort in Part 1 and every 10, 20 and 30 subject enrolled in part 2 (if available) ] [ Designated as safety issue: Yes ]
  • Objective response in GBM tumors as assessed by Macdonald criteria [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Dose limiting toxicity used to estimate the MTD [ Time Frame: 28 Days after last subject enrolled of each cohort in Part 1 and every 10, 20 and 30 subject enrolled in part 2 (if available) ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01475006 on ClinicalTrials.gov Archive Site
  • Clinical benefit rate [ Time Frame: every 6 months ] [ Designated as safety issue: No ]
  • Progressive free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Anti-AMG 595 antibody formation [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
AMG 595 First-in-Human in Recurrent Gliomas
A Phase 1 First-in-Human Study Evaluating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 595 in Subjects With Recurrent Malignant Glioma Expressing Mutant Epidermal Growth Factor Receptor Variant III (EGFRvIII)

This is an open-label, sequential dose exploration study of single agent AMG 595 administered in subjects with recurrent glioblastoma multiforme and/or anaplastic astrocytomas. This study consist of two parts. The dose exploration in Part 1, studies of cohorts of 3 subjects with recurrent Glioblastoma Multiforme (GBM) and/or Anaplastic Astrocytomas (AA) and uses a practical continuous reassessment model [CRM] to guide dose escalation and define the maximum tolerated dose (MTD). The dose expansion in Part 2 will enroll 30 subjects with GBM at a dose no higher than the MTD to further explore the safety, PK, and clinical activity of AMG 595 in this patient population.

Eligible subjects enrolled in the study will receive AMG 595 beginning at study day 1. Following the first two dose of AMG 595 and upon successful completion of a 28 days window for assessing dose limiting toxicities, subject will undergo radiological assessment of their tumors with MRI during week 5. Dosing may resume at week 7 unless there is radiological evidence of progressive disease per Macdonald criteria, the subject becomes intolerant to the study medication, signs and symptoms of clinical progression are evident as determined by the investigator, or the subject withdraws consent.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Advanced Malignant Glioma
  • Anaplastic Astrocytomas
  • Glioblastoma Multiforme
Drug: AMG 595
AMG 595 is an antibody drug conjugated that binds to EGFRvIII.
  • Experimental: Part I Dose Exploration
    Pre-specified nominal doses are proposed in the dose exploration. Intermediate doses may also be used if required based on the CRM design.
    Intervention: Drug: AMG 595
  • Experimental: Part II Dose Expansion
    Dose selected from Part 1 dose exploration
    Intervention: Drug: AMG 595
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
October 2015
June 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Karnofsky performance score > or = 70%
  • Must have pathologically documented, and definitively diagnosed recurrent WHO Grade IV advanced malignant glioblastoma multiforme (Part 1 and Part 2) and/or WHO Grade III anaplastic astrocytoma (Part 1 only).
  • GBM and/or AA tumors expressing EGFRvIII as assessed on archived tissue by IHC staining of sections containing a minimum of 100 evaluable tumor cells.
  • Archived tumor tissue from the initial diagnosis or subsequent relapse(s) of Grade IV advanced malignant glioblastoma multiforme or Grade III anaplastic astrocytoma available for submission to central review.
  • QTcF ≤ 470 msec
  • Hematological function, as follows: Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, Platelet count ≥ 100 x 10^9/L, Hemoglobin > 9 g/dL
  • Renal function, as follows: Estimated glomerular filtration rate using the Modified Diet in Renal Disease (MDRD) equation > 45 mL/min/1.73m^2, Urinary protein quantitative value of < 30 mg/dL in urinalysis or ≤ 1+ on dipstick, unless quantitative protein is < 500 mg in a 24 hr urine sample

Exclusion Criteria:

  • History of central nervous system bleeding as defined by stroke or intraocular bleed (including embolic stroke) within 6 months before enrollment.
  • Evidence of acute intracranial / intratumoral hemorrhage, except for subjects with stable grade 1 hemorrhage.
  • Peripheral sensory neuropathy > Grade 2.
  • Clinically significant ECG changes which obscure the ability to assess the PR, QT, and QRS interval; congenital long QT syndrome.
  • Recent infection requiring intravenous anti-infective treatment that was completed ≤ 14 days before enrollment.
  • Received radiation therapy within 12 weeks before enrollment or has not recovered from the toxic effects of such therapy.
  • Treated previously with bevacizumab or anti-angiogenic therapy for the dose expansion (Part 2) only.
Both
18 Years and older
No
Contact: Amgen Call Center 866-572-6436
United States,   Australia
 
NCT01475006
20090505
No
Amgen
Amgen
Not Provided
Study Director: MD Amgen
Amgen
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP