A Phase I Trial Of The Humanized Anti-GD2 Antibody In Children And Adolescents With Neuroblastoma, Osteosarcoma, Ewing Sarcoma and Melanoma
Relapsed and/or refractory neuroblastoma, osteosarcoma, Ewing sarcoma and melanoma are considered difficult to treat and cure. For this study we are testing the use of a new experimental (investigational) antibody called hu14.18K322A. GD2 is expressed on the surface of most of these tumor types.
Two schedules of hu14.18K322A antibody will be evaluated in this study, (1) daily for four consecutive days schedule every 28 days and (2) once weekly for 4 weeks schedule every 28 days. Approximately 25-40 participants will be required to define the maximum tolerated dose for each schedule. Participants will continue on treatment for a maximum of 4 to 8 courses or until one or more of the criteria for off-treatment are met.
Biological: Anti-GD2 antibody
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial Of The Humanized Anti-GD2 Antibody (HU14.18K322A) In Children And Adolescents With Neuroblastoma, Osteosarcoma, Ewing Sarcoma and Melanoma|
- Determine maximum tolerated dose and dose-limiting toxicity of the humanized monoclonal anti-GD2 antibody, hu14.18K322A, in research participants with neuroblastoma, osteosarcoma, Ewing sarcoma and melanoma. [ Time Frame: within 12 months of the start of therapy ] [ Designated as safety issue: Yes ]
|Study Start Date:||August 2008|
|Estimated Study Completion Date:||June 2018|
|Estimated Primary Completion Date:||June 2017 (Final data collection date for primary outcome measure)|
Experimental: Group 1
Participants who consent to the study will receive Anti-GD2 antibody.
Biological: Anti-GD2 antibody
SJGD2 is a Phase I dose finding study. The primary purpose of this phase I study is to determine the maximum tolerated dose (MTD) and dose-limiting toxicity of the humanized monoclonal anti-GD2 antibody, hu14.18K322A, in research participants with refractory or relapsed neuroblastoma or melanoma (Parts A and B) or osteosarcoma or Ewing sarcoma (Part C).
Initially, in Part A, one research participant will be treated at the lowest dose level of hu14.18K322A antibody [2 mg/m^2 daily for 4 consecutive days every 28 days (1 course)], and if no toxicity is observed then the next participant will be treated at the next dose level. This is continued until the first instance of biological activity (in the form of grade 2 side effects) is observed and from that point on a traditional phase I study design will be followed. A maximum of 4 courses may be given.
Part B: Hu14.18K322A antibody will be administered intravenously (IV) at a starting dose of 50 mg/m^2/dose weekly for 4 doses per course. One course is considered 28 days. A maximum of 8 courses may be given.
Part C: Hu14.18K322A antibody will be administered to 6 patients each with refractory/recurrent osteosarcoma at a maximum tolerated dose (MTD) of 60 mg/m^2 daily for 4 consecutive days every 28 days (Part C1). A cohort of patients with refractory/recurrent osteosarcoma or Ewing sarcoma will also be administered hu14.18K322A antibody at starting dose of 40 mg/m^2/dose weekly for 4 doses per course (Part C2). Participants will continue on treatment for a maximum of 8 courses.
Secondary objectives include:
- Estimate the response rate, within the confines of a phase I study, to the humanized anti-GD2 antibody, hu14.18K322A.
- Evaluate the pharmacokinetics of hu14.18K322A.
- Examine whether or not human anti-human antibodies (HAHA) develop in participants receiving hu14.18K322A.
- Assess the tolerability of the hu14.18K322A at the MTD of the daily x4 and the weekly dosing in patients with refractory or recurrent osteosarcoma.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00743496
|Contact: Michael Bishop, MDfirstname.lastname@example.org|
|United States, Tennessee|
|St. Jude Children's Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Michael Bishop, MD 866-278-5833 email@example.com|
|Principal Investigator: Michael Bishop, MD|
|Principal Investigator:||Michael Bishop, MD||St. Jude Children's Research Hospital|