AMG 595 First-in-Human in Recurrent Gliomas

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Amgen
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01475006
First received: September 29, 2011
Last updated: October 17, 2014
Last verified: October 2014
  Purpose

This is an open-label, sequential dose exploration study of single agent AMG 595 administered in subjects with recurrent glioblastoma multiforme (GBM) and/or anaplastic astrocytomas (AA). The purpose of the study is to evaluate safety, tolerability, and pharmacokinetics (PK) of AMG 595, and also to evaluate the objective response rate in subjects receiving AMG 595. This study will be conducted in two parts. Part 1 will explore doses of AMG 595 in subjects with recurrent GBM and/or AA. Part 2 (dose expansion) will examine the MTD established in Part 1 in subjects with recurrent GBM.


Condition Intervention Phase
Advanced Malignant Glioma
Anaplastic Astrocytomas
Glioblastoma Multiforme
Drug: AMG 595
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 60
Study Start Date: November 2011
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: AMG 595
AMG 595 is an antibody drug conjugate that binds to EGFRvIII.
Experimental: Part II Dose Expansion
Dose selected from Part 1 dose exploration
Drug: AMG 595
AMG 595 is an antibody drug conjugate that binds to EGFRvIII.

Detailed Description:

This study of AMG 595 will be conducted in two parts: Part 1 (dose exploration) and Part 2 (dose expansion). Part 1 of the study is in subjects with recurrent glioblastoma multiforme (GBM) and/or anaplastic astrocytomas (AA), and Part 2 is examining the MTD in subjects with recurrent GBM. Approximately 30-40 subjects may be enrolled in Part 1, and up to 36 subjects may be enrolled in Part 2. The dose of AMG 595 utilized in Part 2 will be dependent upon data obtained in Part 1 of the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  • Subjects with recurrent disease (confirmed by MRI and evaluable by Macdonald criteria) at the time of first or second recurrence or progression following initial definitive therapy(s)
  • 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.
  • For Part 1 (dose escalation): Treatment with bevacizumab or antiangiogenic therapy within 4 weeks before enrollment, or for Part 2 (dose expansion): any prior treatment with bevacizumab or antiangiogenic therapy.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01475006

Contacts
Contact: Amgen Call Center 866-572-6436

Locations
United States, California
Research Site Recruiting
Los Angeles, California, United States, 90024
United States, Massachusetts
Research Site Recruiting
Boston, Massachusetts, United States, 02115
United States, Ohio
Research Site Recruiting
Cincinnati, Ohio, United States, 45267
Australia, Victoria
Research Site Recruiting
Parkville, Victoria, Australia, 3052
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01475006     History of Changes
Other Study ID Numbers: 20090505
Study First Received: September 29, 2011
Last Updated: October 17, 2014
Health Authority: Australia: Royal Adelaide Hospital Research Ethics Committee
Australia:Melbourne Health Office for Research
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Amgen:
Epidermal Growth Factor Receptor Variant III
EGFRvIII
Glioma
Anaplastic Astrocytomas
Glioblastoma Multiforme
Antibody drug conjugate
brain tumor

Additional relevant MeSH terms:
Astrocytoma
Glioblastoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 20, 2014