Trebananib in Treating Younger Patients With Relapsed or Refractory Solid Tumors, Including Central Nervous System Tumors
This phase I trial studies the side effects and the best dose of trebananib in treating patients with relapsed or refractory solid tumors, including central nervous system tumors. Trebananib may stop the growth of tumor cells by blocking blood flow to the tumor.
Recurrent Childhood Anaplastic Astrocytoma
Recurrent Childhood Anaplastic Oligoastrocytoma
Recurrent Childhood Anaplastic Oligodendroglioma
Recurrent Childhood Cerebellar Astrocytoma
Recurrent Childhood Cerebral Astrocytoma
Recurrent Childhood Diffuse Astrocytoma
Recurrent Childhood Fibrillary Astrocytoma
Recurrent Childhood Gemistocytic Astrocytoma
Recurrent Childhood Giant Cell Glioblastoma
Recurrent Childhood Glioblastoma
Recurrent Childhood Gliomatosis Cerebri
Recurrent Childhood Gliosarcoma
Recurrent Childhood Oligoastrocytoma
Recurrent Childhood Oligodendroglioma
Recurrent Childhood Pilocytic Astrocytoma
Recurrent Childhood Pineoblastoma
Recurrent Childhood Pleomorphic Xanthoastrocytoma
Recurrent Childhood Protoplasmic Astrocytoma
Recurrent Childhood Subependymal Giant Cell Astrocytoma
Recurrent Childhood Visual Pathway and Hypothalamic Glioma
Recurrent Childhood Visual Pathway Glioma
Unspecified Childhood Solid Tumor, Protocol Specific
Procedure: dynamic contrast-enhanced magnetic resonance imaging
Other: pharmacological study
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A PHASE 1 STUDY OF AMG 386 (IND# 114215), AN ANGIOPOIETIN NEUTRALIZING PEPTIBODY, IN CHILDREN WITH RELAPSED OR REFRACTORY SOLID TUMORS, INCLUDING CNS TUMORS|
- Toxicity of AMG 386 as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- MTD based on the incidence of DLT as assessed by NCI CTCAE version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Pharmacokinetic (PK) parameters of AMG 386 [ Time Frame: At baseline, at days 1, 8, 15, and 22 of course 1 ] [ Designated as safety issue: No ]The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
- Disease response assessed according to RECIST version 1.1 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Reported descriptively.
- Changes in vascular permeability relative to baseline as evaluated by MRI [ Time Frame: From baseline to up to 1 year ] [ Designated as safety issue: No ]Reported descriptively.
|Study Start Date:||February 2012|
|Estimated Primary Completion Date:||April 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (trebananib)
Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Other Names:Procedure: dynamic contrast-enhanced magnetic resonance imaging
Other Name: DCE-MRIOther: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
I. To estimate the maximum-tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of trebananib (AMG 386) administered as a weekly intravenous infusion to children with recurrent or refractory solid tumors.
II. To determine the tolerability of the solid tumor MTD and/or RP2D of AMG 386 in children with central nervous system (CNS) tumors.
III. To define and describe the toxicities of AMG 386 administered on this schedule.
IV. To characterize the pharmacokinetics and immunogenicity of AMG 386 in children with refractory cancer.
V. To measure changes in vascular permeability relative to baseline, evaluated by magnetic resonance imaging (MRI) perfusion, following AMG 386 administration in pediatric patients with CNS tumors.
I. To preliminarily define the antitumor activity of AMG 386 within the confines of a Phase 1 study.
II. To measure biologic markers of angiogenesis with potential for correlation with disease response.
OUTLINE: This is a multicenter, dose-escalation study (part 1) followed by a safety and imaging study (part 2).
Patients receive trebananib intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection at baseline and periodically during study for pharmacokinetic and immunogenicity studies. Blood may also be collected for correlative studies. Some patients also undergo dynamic contrast-enhanced (DCE)-MRI at baseline and periodically during study.
After completion of study treatment, patients are followed up every 3 to 6 months for up to 1 year.