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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03296696




Registration number
NCT03296696
Ethics application status
Date submitted
18/09/2017
Date registered
28/09/2017

Titles & IDs
Public title
Study of AMG 596 in Patients With EGFRvIII Positive Glioblastoma
Scientific title
Phase 1/1b Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 596 as Monotherapy and in Combination With AMG 404 in Subjects With Glioblastoma or Malignant Glioma Expressing Mutant Epidermal Growth Factor Receptor Variant III (EGFRvIII)
Secondary ID [1] 0 0
2017-001658-32
Secondary ID [2] 0 0
20160132
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma or Malignant Glioma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AMG 596
Treatment: Drugs - AMG 404

Experimental: Dose exploration - Dose exploration of the intervention, AMG 596 alone or in combination with AMG 404

Experimental: Dose expansion - Dose expansion of the intervention, AMG 596 alone or in combination with AMG 404


Treatment: Drugs: AMG 596
Drug

Treatment: Drugs: AMG 404
Drug
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Dose-Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Up to 28 days
Primary outcome [2] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Timepoint [2] 0 0
First dose of study drug until 37 days after last dose or end of study, whichever is earlier. Duration with median (min, max) in months: 3.32 (1.28, 29.31)
Primary outcome [3] 0 0
Number of Participants With Treatment-Related Adverse Events (AEs)
Timepoint [3] 0 0
First dose of study drug until 37 days after last dose or end of study, whichever is earlier. Duration with median (min, max) in months: 3.32 (1.28, 29.31)
Secondary outcome [1] 0 0
Average Steady-state Concentration (Css) of Serum AMG 596
Timepoint [1] 0 0
Cycle1 to Cycle2 (cycle=14 days in single participant cohorts,42 days in multiple participant cohorts):7-days on/7-days off dosing and 28-days on/14-days off dosing:pre-infusion,2,6,8,24,48hrs post-infusion start,0.5,2,4,8,24hrs post infusion end
Secondary outcome [2] 0 0
Area Under the Concentration-time Curve (AUC) for Serum AMG 596
Timepoint [2] 0 0
Cycle1 to Cycle2 (cycle=14 days in single participant cohorts,42 days in multiple participant cohorts):7-days on/7-days off dosing and 28-days on/14-days off dosing:pre-infusion,2,6,8,24,48hrs post-infusion start,0.5,2,4,8,24hrs post infusion end
Secondary outcome [3] 0 0
Clearance for Serum AMG 596
Timepoint [3] 0 0
Cycle1 to Cycle2 (cycle=14 days in single participant cohorts,42 days in multiple participant cohorts):7-days on/7-days off dosing and 28-days on/14-days off dosing:pre-infusion,2,6,8,24,48hrs post-infusion start,0.5,2,4,8,24hrs post infusion end
Secondary outcome [4] 0 0
Apparent Volume of Distribution at Steady-State for Serum AMG 596
Timepoint [4] 0 0
Cycle1 to Cycle2 (cycle=14 days in single participant cohorts,42 days in multiple participant cohorts):7-days on/7-days off dosing and 28-days on/14-days off dosing:pre-infusion,2,6,8,24,48hrs post-infusion start,0.5,2,4,8,24hrs post infusion end
Secondary outcome [5] 0 0
Terminal Half-life (t1/2) Associated With Lambda z (?z) for Serum AMG 596
Timepoint [5] 0 0
Cycle1 to Cycle2 (cycle=14 days in single participant cohorts,42 days in multiple participant cohorts):7-days on/7-days off dosing and 28-days on/14-days off dosing:pre-infusion,2,6,8,24,48hrs post-infusion start,0.5,2,4,8,24hrs post infusion end
Secondary outcome [6] 0 0
Number of Participants With an Objective Response (OR) Per Modified Response Assessment in Neuro-Oncology Criteria (RANO) Criteria With AMG 596 Monotherapy
Timepoint [6] 0 0
Baseline up to 12 Months
Secondary outcome [7] 0 0
Time to Response With AMG 596 Monotherapy
Timepoint [7] 0 0
Up to 12 months
Secondary outcome [8] 0 0
Response Duration With AMG 596 Monotherapy
Timepoint [8] 0 0
Up to 30 months
Secondary outcome [9] 0 0
Time to Progression (TTP) With AMG 596 Monotherapy
Timepoint [9] 0 0
Up to 12 Months
Secondary outcome [10] 0 0
Progression-free Survival (PFS) With AMG 596 Monotherapy
Timepoint [10] 0 0
Up to 12 months

Eligibility
Key inclusion criteria
Inclusion Criteria

* Eastern Cooperative Oncology Group (ECOG, Appendix G) Performance Status of less than or equal to 1
* Life expectancy of at least 3 months, in the opinion of the investigator.
* Must have pathologically documented, and definitively diagnosed World Health Organization (WHO) grade 4, glioblastoma or lower grade malignant gliomas with epidermal growth factor receptor variant III (EGFRvIII) positive tumor
* Must have recurrent disease confirmed by magnetic resonance imaging (MRI) (Group 1) or completed standard of care (SoC) therapy such as surgery with adjuvant radiochemotherapy with or without maintenance temozolomide according to local standards for newly diagnosed disease (Group 2)
* Hematological function as follows:

* Absolute neutrophil count (ANC) greater than 1500/mm3 (1.5 × 10 9/L)
* Platelet count greater than 100,000 mm3 (100 × 10 9/L)
* White blood cell (WBC) count greater than 3 × 10 9/L
* Hemoglobin greater than 9.0 g/dL
* Renal function as follows: serum creatinine less than 2.0 mg/dL and estimated glomerular filtration rate greater than or equal to 60 mL/min/1.73 m2 by Modification of Diet in Renal Disease (MDRD) and urine protein quantitative value of less than 30 mg/dL in urinalysis or less than or equal to 1+ on dipstick
* Hepatic function as follows:

* Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) less than or equal to 3.0 x upper limit of normal (ULN)
* Bilirubin less than or equal to 1.5 x ULN (unless considered due to Gilbert's syndrome or hemolysis)
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* History or evidence of central nervous system bleeding as defined by stroke or intraocular bleed (including embolic stroke) not associated with any antitumor surgery within 6 months before enrolment
* Evidence of acute intracranial / intratumoral hemorrhage, except for subjects with stable grade 1 hemorrhage or fresh biopsy
* Known hypersensitivity to immunoglobulins or to any other component of the investigational product (IP) formulation
* Prior malignancy (other than in situ cancer) unless treated with curative intent and without evidence of disease for > 2 years before screening
* Active infection requiring intravenous antibiotics that was completed less than 1 week of study enrolment (day 1) with the exemption of prophylactic antibiotics for long line insertion or biopsy
* Known positive test for human immunodeficiency virus (HIV)
* Active hepatitis B and C based on the following results:

* Positive for hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B)
* Negative HepBsAg and positive for hepatitis B core antibody: hepatitis B virus deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B
* Positive hepatitis C virus antibody (HepCAb): hepatitis C virus ribonucleic acid (RNA) by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C Common terminology criteria for adverse events
* Unresolved toxicities from prior antitumor therapy, defined as not having resolved to common terminology criteria for adverse events (CTCAE), version 4.0 grade 1 (with the exception of myelosuppression, eg, neutropenia, anemia, thrombocytopenia), or to levels dictated in the eligibility criteria with the exception of alopecia or toxicities from prior antitumor therapy that are considered irreversible (defined as having been present and stable for greater than 2 months) which may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by both the investigator and sponsor
* Antitumor therapy (chemotherapy, antibody therapy, molecular-targeted therapy, or investigational agent) within 14 days (Group 2 subjects) or 5 half-lives (whichever is longer: for Group 1 subjects) of day 1. Avastin, Pembrolizumab must be stopped 14 days prior to day 1
* Treatment with non-topical systemic corticosteroids within 14 days before enrollment (day 1) (exemption: prophylactic treatment with dexamethasone as defined in section 6.5, and systemic corticosteroid doses of = 2 mg of dexamethasone (or equivalent) per day after consultation with Sponsor,)
* Prior participation in an investigational study (drug, procedure or device) within 21 days of study day 1
* Major surgery within 7 days of study day 1 with the exception of biopsy and long line insertion
* History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
* Male and female of reproductive potential who are unwilling to practice highly effective method(s) of birth control while on study and through 30 days after receiving the last dose of AMG 596 and through 4 months (120 days) after receiving the last dose of AMG 404.

* Criteria for women of non-reproductive potential is as follows:
* Postmenopausal as defined as:
* Age of 55 years with cessation of menses for 12 months or more, OR
* Age < 55 years and no spontaneous menses for at least 2 years, OR
* Age < 55 years and spontaneous menses within the past year, but currently amenorrheic (eg, spontaneous or secondary to chemotherapy) AND with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone level > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) according to the definition of "postmenopausal range" for the laboratory involved; OR
* History of hysterectomy; OR
* History of bilateral oophorectomy
* Highly effective methods of birth control include sexual abstinence (male, female); vasectomy; bilateral tubal ligation/occlusion; hormonal birth control or intrauterine device (IUD) (female).
* Female who is lactating/breastfeeding or who plans to breastfeed while on study through 30 days after receiving the last dose of AMG 596 and through 4 months (120 days) after receiving the last dose of AMG 404.
* Female with a positive pregnancy test.
* Female planning to become pregnant while on study through 30 days after receiving the last dose of AMG 596 and through 4 months (120 days) after receiving the last dose of AMG 404 infusion.
* Male who is unwilling to abstain from sperm donation while on study through 30 days after receiving the last dose of AMG 596 and through 4 months (120 days) after receiving the last dose of AMG 404.
* Subjects likely to not be available to complete all protocol required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge.
* History of solid organ transplantation. Prior treatment with anti-PD-1, anti-PD-L1, CTLA-4 or other checkpoint inhibitor drugs
* Prior treatment with AMG 596 monotherapy arm is not eligible to enroll in the combination therapy arm.
* Live vaccine therapies within 4 weeks prior to study drug administration
* Evidence of interstitial lung disease or active, non-infectious pneumonitis
* History of any immune-related colitis. Infectious colitis is allowed if evidence of adequate treatment and clinical recovery exists and at least 3 months interval observed since diagnosis of colitis.
* Active or history of any autoimmune disease or immunodeficiencies. Subjects with Type I diabetes, vitiligo, psoriasis, hypo-or hyper-thyroid disease not requiring immune-suppressive treatment are permitted.
* Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or cardiac arrhythmia requiring medication.

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
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/04/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/08/2021
Sample size
Target
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Royal North SHore Hospital - St Leonards
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
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
New York
Country [3] 0 0
France
State/province [3] 0 0
Villejuif
Country [4] 0 0
Germany
State/province [4] 0 0
Dresden
Country [5] 0 0
Germany
State/province [5] 0 0
Hamburg
Country [6] 0 0
Germany
State/province [6] 0 0
Würzburg
Country [7] 0 0
Netherlands
State/province [7] 0 0
Amsterdam
Country [8] 0 0
Spain
State/province [8] 0 0
Cataluña

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Available to whom?
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.amgen.com/datasharing


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03296696