malignent brain tumor spongioblastoom
Conditions
Interventions
All subjects will be hospitalized for the following periods:
Cycle 1:
* For the first 7 days of AMG 596 monotherapy (Arm 1)
* For the first 8 days of AMG 596 in combination with AMG 404 (Arm 2), hence
EGFRvIII
Glioblastoma
Phase 1/1b
Sponsors
Amgen
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: * Written informed consent, subject is at least 18 years of age * Eastern Cooperative Oncology Group (ECOG, Appendix F) Performance Status of * 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) * Group 1 subjects must have * 1 index lesion by modified RANO criteria, exemption: non-measurable disease is allowed for subjects with re-surgery (surgery for recurrent disease) before start of screening * Group 2 subjects must have radiographically measurable disease, or non-measurable disease or both at the time of enrollment are allowedConfirmed EGFRvIII positivity at time of study enrollment * Hematological, hepatic and renal function as described in protocol page 35
Exclusion criteria
Exclusion criteria: History or evidence of central nervous system bleeding within 6 months before enrollment -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 IP formulation -Prior malignancy (other than in situ cancer) unless treated with curative intent and without evidence of disease for > 2 years before screening -Infection requiring intravenous antibiotics that was completed class II), unstable angina, or cardiac arrhythmia requiring medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint: * Dose limiting toxicities (DLT), treatment-emergent adverse events, treatment-related adverse events and clinically significant changes in vital signs, physical examinations, and clinical laboratory tests | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoint(s): * Serum PK parameters for AMG 596 including, but not limited to, average steady-state concentration (Css), area under the concentration-time curve (AUC), clearance, volume of distribution and half-life (t1/2) for serum AMG 596 * PK parameters of AMG 404 including, but not limited to, maximum observed serum concentration (Cmax), time to achieve Cmax (tmax) and AUC. ** PK parameters for AMG 596 dosed in combination with AMG 404 including, but not limited to, average steady-state concentration (Css), area under the concentration-time curve (AUC), clearance, volume of distribution and half-life (t1/2) for serum AMG 596 * Objective response (OR) as per modified RANO, time to response, response duration and time to progression (TTP); progression met AMG 596 monotherapie of AMG 596 in combinatie met AMG 404 | — |
Countries
Australia, France, Germany, Netherlands, Spain, United States of America
Outcome results
None listed