AMG 595 First-in-Human in Recurrent Gliomas

NCT01475006 | Completed Phase 1

• 1 other identifier: 20090505
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 4

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.

Conditions

Advanced Malignant Glioma; Anaplastic Astrocytomas; Glioblastoma Multiforme

Keywords

Epidermal Growth Factor Receptor Variant III; EGFRvIII; Glioma; Anaplastic Astrocytomas; Glioblastoma Multiforme; Antibody drug conjugate; brain tumor

Outcome Measures

Primary Outcomes (4)

• Clinically significant or > or = to Grade 3 CTCAE changes in safety laboratory tests, physical exams, ECGs or vital signs

  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)

• PK Parameters: Cmax, Cmin, and if feasible half life - 8 time points up to 6 weeks

  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)

• Objective response in GBM tumors as assessed by Macdonald criteria

  3 years

• Dose limiting toxicity used to estimate the MTD

  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 Outcomes (4)

• Clinical benefit rate

  every 6 months

• Progressive free survival

  3 years

• Overall survival

  3 years

• Anti-AMG 595 antibody formation

  3 years

Study Arms (2)

Part I Dose Exploration

EXPERIMENTAL

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

Part II Dose Expansion

EXPERIMENTAL

Dose selected from Part 1 dose exploration

Drug: AMG 595

Interventions

AMG 595 DRUG

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

Part I Dose Exploration; Part II Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (4)

Research Site

Los Angeles, California, 90024, United States

Location

Research Site

Boston, Massachusetts, 02115, United States

Location

Research Site

Cincinnati, Ohio, 45267, United States

Location

Research Site

Parkville, Victoria, 3052, Australia

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Astrocytoma; Glioblastoma; Glioma; Brain Neoplasms

Interventions

AMG 595

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2011
• First Posted: November 21, 2011
• Study Start: February 1, 2012
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: April 15, 2016

Record last verified: 2016-04

Locations

AU (1); US (3)