We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

AMG 595 First-in-Human in Recurrent Gliomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01475006
Recruitment Status : Completed
First Posted : November 21, 2011
Last Update Posted : April 15, 2016
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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 or disease Intervention/treatment Phase
Advanced Malignant Glioma Anaplastic Astrocytomas Glioblastoma Multiforme Drug: AMG 595 Phase 1

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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)
Study Start Date : February 2012
Primary Completion Date : April 2016
Study Completion Date : April 2016


Arms and Interventions

Arm Intervention/treatment
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.


Outcome Measures

Primary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. Objective response in GBM tumors as assessed by Macdonald criteria [ Time Frame: 3 years ]
  4. 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) ]

Secondary Outcome Measures :
  1. Clinical benefit rate [ Time Frame: every 6 months ]
  2. Progressive free survival [ Time Frame: 3 years ]
  3. Overall survival [ Time Frame: 3 years ]
  4. Anti-AMG 595 antibody formation [ Time Frame: 3 years ]

Eligibility Criteria

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:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

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): NCT01475006


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

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01475006     History of Changes
Other Study ID Numbers: 20090505
First Posted: November 21, 2011    Key Record Dates
Last Update Posted: April 15, 2016
Last Verified: April 2016

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:
Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue