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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01475006




Registration number
NCT01475006
Ethics application status
Date submitted
29/09/2011
Date registered
21/11/2011
Date last updated
15/04/2016

Titles & IDs
Public title
AMG 595 First-in-Human in Recurrent Gliomas
Scientific 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)
Secondary ID [1] 0 0
20090505
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Malignant Glioma 0 0
Anaplastic Astrocytomas 0 0
Glioblastoma Multiforme 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AMG 595

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.

Experimental: Part II Dose Expansion - Dose selected from Part 1 dose exploration


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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Clinically significant or > or = to Grade 3 CTCAE changes in safety laboratory tests, physical exams, ECGs or vital signs
Timepoint [1] 0 0
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)
Primary outcome [2] 0 0
PK Parameters: Cmax, Cmin, and if feasible half life - 8 time points up to 6 weeks
Timepoint [2] 0 0
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)
Primary outcome [3] 0 0
Objective response in GBM tumors as assessed by Macdonald criteria
Timepoint [3] 0 0
3 years
Primary outcome [4] 0 0
Dose limiting toxicity used to estimate the MTD
Timepoint [4] 0 0
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 [1] 0 0
Clinical benefit rate
Timepoint [1] 0 0
every 6 months
Secondary outcome [2] 0 0
Progressive free survival
Timepoint [2] 0 0
3 years
Secondary outcome [3] 0 0
Overall survival
Timepoint [3] 0 0
3 years
Secondary outcome [4] 0 0
Anti-AMG 595 antibody formation
Timepoint [4] 0 0
3 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01475006
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications