Abstract
Randomized multicenter double-blind phase II trial: The immunological adjuvant OPT-821 with or without a trivalent ganglioside vaccine in metastatic sarcoma patients following metastasectomy
Journal of clinical oncology, Vol.30(15_suppl), pp.TPS10103-TPS10103
05/20/2012
DOI: 10.1200/jco.2012.30.15_suppl.tps10103
Abstract
TPS10103
Background: The gangliosides GM2, GD2, and GD3 are strongly expressed in sarcoma and represent novel antitumor targets. We have demonstrated the safety and immunogenicity of individual monovalent ganglioside conjugate vaccines when administered with OPT821, a synthetic saponin adjuvant that augments the T-cell response. Antitumor effects are observed with anti-ganglioside antibodies in preclinical models, with greatest benefit seen in the micrometastatic setting. Patients (pts) with metastatic sarcoma rendered disease-free by surgery are at high risk for disease recurrence, with no therapy demonstrated to improve outcomes. Therefore, this population is ideally suited to test the efficacy of vaccine induced anti-ganglioside antibodies. We thus initiated this randomized double-blind phase II study of OPT821 with or without a trivalent ganglioside vaccine composed of GM2, GD2 lactone and GD3 lactone conjugated to KLH, an immunogenic carrier protein. Methods: A total of 134 pts will be randomized on a 1:1 basis stratified by disease state (relapsed disease vs metastasis at time of diagnosis), disease-free interval and number of relapses. Key inclusion criteria include stage IV sarcoma (locoregional recurrence is not sufficient) rendered disease-free following surgery or multi-modality therapy, no more than 8 weeks since surgery, and no continuous use of anti-inflammatory medications. Pts with Ewings sarcoma, GIST and rhabdomyosarcoma (except pleomorphic/anaplastic) are ineligible. Eligible pts will receive 10 subcutaneous injections in the outpatient setting over 84 weeks. The primary endpoint is progression-free survival (PFS). Secondary objectives include overall survival (OS) and 1- and 3-year PFS rate. Exploratory objectives include correlation of serologic response to outcome, comparison of tumor ganglioside expression at baseline and at recurrence, and analysis of circulating tumor cells. Enrollment began in July 2010. As of January 1, 2012, 83 patients had been recruited from 12 participating sites. Clinicaltrials.gov#: NCT01141491. Funded by Mabvax Therapeutics and NIH (R21CA13386).
Details
- Title: Subtitle
- Randomized multicenter double-blind phase II trial: The immunological adjuvant OPT-821 with or without a trivalent ganglioside vaccine in metastatic sarcoma patients following metastasectomy
- Creators
- Richard D. Carvajal - Memorial Sloan Kettering Cancer CenterRashmi Chugh - University of Michigan–Ann ArborMohammed M. Milhem - University of IowaChristopher W. Ryan - Oregon Health & Science UniversitySuzanne George - Dana-Farber Cancer InstituteBartosz Chmielowski - University of California, Los AngelesMark Agulnik - Northwestern UniversityEve T. Rodler - Seattle Cancer Care AllianceAnthony D. Elias - University of Colorado Cancer CenterG. Thomas Budd - Cleveland ClinicHussein Tawbi - University of Pittsburgh Medical CenterSujana Movva - Emory University Hospital MidtownBrian Andrew Van Tine - Washington University in St. LouisMark Andrew Dickson - Memorial Sloan Kettering Cancer CenterMartee Leigh Hensley - Memorial Sloan Kettering Cancer CenterMary Louise Keohan - Memorial Sloan Kettering Cancer CenterWilliam D. Tap - Memorial Sloan Kettering Cancer CenterCathryn M. Bennett - Mabvax TherapeuticsRobert G. Maki - Icahn School of Medicine at Mount SinaiGary K. Schwartz - Memorial Sloan Kettering Cancer Center
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.30(15_suppl), pp.TPS10103-TPS10103
- DOI
- 10.1200/jco.2012.30.15_suppl.tps10103
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 05/20/2012
- Academic Unit
- Internal Medicine; Hematology, Oncology, and Blood & Marrow Transplantation
- Record Identifier
- 9984363164502771
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