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Study of AMG 596 in Patients With EGFRvIII Positive Glioblastoma

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03296696
Recruitment Status : Active, not recruiting
First Posted : September 28, 2017
Last Update Posted : September 9, 2020
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:

This is a Phase 1/1b Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 596 monotherapy or in combination with AMG 404 in Subjects with Glioblastoma or Malignant Glioma Expressing Mutant Epidermal Growth Factor Receptor Variant III (EGFRvIII).

This is a first in human (FIH), open-label, sequential-dose-escalation study in subjects with EGFRvIII-positive glioblastoma or malignant glioma. This study will enroll 2 groups of subjects according to disease stage, recurrent disease (Group 1) and maintenance treatment after SoC in newly diagnosed disease (Group 2).


Condition or disease Intervention/treatment Phase
Glioblastoma or Malignant Glioma Drug: AMG 596 Drug: AMG 404 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Bayesian logistic regression model
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : April 18, 2018
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : June 16, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose exploration
Dose exploration of the intervention, AMG 596 alone or in combination with AMG 404
Drug: AMG 596
Drug

Drug: AMG 404
Drug

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

Drug: AMG 404
Drug




Primary Outcome Measures :
  1. Subject grade of dose limiting toxicities (DTLs) [ Time Frame: 12 months ]
    Subject grade of dose limiting toxicities is the occurrence of any of the toxicities during the DLT evaluation period if judged by the investigator to be related to the administration of AMG 596 and AMG 404

  2. Number of subject with treatment-emergent adverse events [ Time Frame: 12 months ]
  3. Number of subjects with treatment-related adverse events [ Time Frame: 12 months ]
  4. Number of subjects with clinically significant changes in vital signs [ Time Frame: 12 months ]
  5. Number of subjects with clinically significant changes in physical examinations [ Time Frame: 12 months ]
  6. Number of subjects with clinically significant changes in clinical laboratory tests [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Average steady-state concentration (Css) for serum AMG 596 [ Time Frame: 12 months ]
  2. Area under the concentration-time curve (AUC) for serum AMG 596 [ Time Frame: 12 months ]
  3. Clearance for serum AMG 596 [ Time Frame: 12 months ]
  4. Volume of distribution for serum AMG 596 [ Time Frame: 12 months ]
  5. Half-life (t1/2) for serum AMG 596 [ Time Frame: 12 months ]
  6. Maximum abserved serum concentration (Cmax) for AMG 404 [ Time Frame: 12 months ]
  7. Time to achieve Cmax (tmax) for AMG 404 [ Time Frame: 12 months ]
  8. Area under the concentration-time curve (AUC) for AMG 404 [ Time Frame: 12 months ]
  9. Average steady-state concentration (Css) for serum AMG 596 in combination with AMG 404 [ Time Frame: 12 months ]
  10. Area under the concentration-time curve (AUC) for serum AMG 596 in combination with AMG 404 [ Time Frame: 12 months ]
  11. Clearance for serum AMG 596 in combination with AMG 404 [ Time Frame: 12 months ]
  12. Half-life (t1/2) for serum AMG 596 in combination with AMG 404 [ Time Frame: 12 months ]
  13. Objective response (OR) as per modified RANO for AMG 596 [ Time Frame: 6 and 12 months ]
    Objective response (OR) as per modified RANO (Response Assessment in Neuro-Oncology Criteria).

  14. Time to response for serum AMG 596 in combination with AMG 404 [ Time Frame: 6 and 12 months ]
  15. Response duration for serum AMG 596 in combination with AMG 404 [ Time Frame: 6 and 12 months ]
  16. Time to progression (TTP) for serum AMG 596 in combination with AMG 404 [ Time Frame: 6 and 12 months ]
  17. Progression free survival (PFS) at 6 and 12 months after treatment initiation with AMG 596 monotherapy [ Time Frame: 6 and 12 months ]
  18. Progression free survival (PFS) at 6 and 12 months after treatment initiation with AMG 596 in combination with AMG 404 [ Time Frame: 6 and 12 months ]
  19. Objective response (OR) as per modified RANO with AMG 596 monotherapy [ Time Frame: 6 and 12 months ]
  20. Time to response with AMG 596 monotherapy [ Time Frame: 6 and 12 months ]
  21. Response duration with AMG 596 monotherapy [ Time Frame: 6 and 12 months ]
  22. Time to progression (TTP) with AMG 596 monotherapy [ Time Frame: 6 and 12 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 EGFRvIII positive tumor
  • Must have recurrent disease confirmed by MRI (Group 1) or completed 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 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)

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
  • Known hypersensitivity to immunoglobulins or to any other component of the IP formulation
  • 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 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 RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C
  • Unresolved toxicities from prior antitumor therapy, defined as not having resolved to 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
  • Female with a positive pregnancy test.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03296696


Locations
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United States, California
Research Site
Los Angeles, California, United States, 90095
United States, New York
Research Site
New York, New York, United States, 10065
Australia, New South Wales
Research Site
Saint Leonards, New South Wales, Australia, 2065
Australia, Victoria
Research Site
Melbourne, Victoria, Australia, 3000
France
Research Site
Villejuif, France, 94805
Germany
Research Site
Dresden, Germany, 01307
Research Site
Hamburg, Germany, 20246
Research Site
Würzburg, Germany, 97080
Netherlands
Research Site
Amsterdam, Netherlands, 1081 HV
Spain
Research Site
Badalona, Cataluña, Spain, 08916
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03296696    
Other Study ID Numbers: 20160132
2017-001658-32 ( EudraCT Number )
First Posted: September 28, 2017    Key Record Dates
Last Update Posted: September 9, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: 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.
Access Criteria: 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.
URL: https://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
Phase 1/1b
EGFRvIII-positive glioblastoma or malignant glioma
safety and tolerability
AMG 596
Additional relevant MeSH terms:
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Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue