AMG 595 First-in-Human in Recurrent Gliomas

NCT ID: NCT01475006

Last Updated: 2016-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2016-04-30

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.

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.

Conditions

Advanced Malignant Glioma; Anaplastic Astrocytomas; Glioblastoma Multiforme

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

AMG 595

Intervention Type: DRUG

AMG 595 is an antibody drug conjugate that binds to EGFRvIII.

Part II Dose Expansion

Dose selected from Part 1 dose exploration

Group Type: EXPERIMENTAL

AMG 595

Intervention Type: DRUG

AMG 595 is an antibody drug conjugate that binds to EGFRvIII.

Interventions

AMG 595

AMG 595 is an antibody drug conjugate that binds to EGFRvIII.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Research Site

Los Angeles, California, United States

Research Site

Boston, Massachusetts, United States

Research Site

Cincinnati, Ohio, United States

Research Site

Parkville, Victoria, Australia

Countries

United States; Australia

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20090505

Identifier Type: -

Identifier Source: org_study_id