AMG 595 First-in-Human in Recurrent Gliomas
This study is currently recruiting participants.
Verified November 2012 by Amgen
Sponsor:
Amgen
Information provided by:
Amgen
ClinicalTrials.gov Identifier:
NCT01475006
First received: September 29, 2011
Last updated: November 28, 2012
Last verified: November 2012
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Purpose
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.
| 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: | May 2014 |
| Estimated Primary Completion Date: | January 2014 (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 conjugated 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 conjugated that binds to EGFRvIII.
|
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.
- 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.
Contacts and Locations
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, 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: | Global Development Leader, Amgen Inc. |
| ClinicalTrials.gov Identifier: | NCT01475006 History of Changes |
| Other Study ID Numbers: | 20090505 |
| Study First Received: | September 29, 2011 |
| Last Updated: | November 28, 2012 |
| 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, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type |
Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Mitogens Mitosis Modulators Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 16, 2013