Entry Detail
| General information | |
| Database: | DB00577 |
| Objective: | They conducted a phase II trial to evaluate the effectiveness of imatinib for patients with recurrent ESFT or DSRCT expressing KIT and/or PDGFRalpha. |
| Authors: | Chao J, et al |
| Title: | Phase II clinical trial of imatinib mesylate in therapy of KIT and/or PDGFRalphaexpressing Ewing sarcoma family of tumors and desmoplastic small round cell tumors. |
| Journal: | Anticancer Res. |
| Year: | 2010 |
| PMID: | 20332468 |
| Trial Design | |
| Clinical Trial Id: | NCT00062205 |
| Agent: | imatinib mesylate |
| Target: | Abl Plateletderived growth factor receptor Mast/stem cell growth factor receptor |
| Cancer Type: | soft tissue sarcomas |
| Cancer Subtype: | KIT and/or PDGFR¦Áexpressing Ewing Sarcoma Family of Tumors and Desmoplastic Small Round Cell Tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase II Clinical Trial |
| Key Patients Feature: | Patients were eligible if were more than and equal to 16 years ofage with recurrent ESFT and DSRCT, and immunohistochemicalevidence of expression more than and equal to 2+/4+ for either KIT or PDGFR¦Á aspreviously described (19). KIT and PDGFR¦Á expression for allpatients were confirmed by a central pathologist. Patients wererequired to have an ECOG performance status of less than and equal to 2 and estimatedsurvival of at least 2 months. Adequate organ function for inclusionwas defined by creatinine <1.5 times the institutional upper limit ofnormal, absolute neutrophil count more than and equal to 1500/¦ÌL, platelet countmore than and equal to 100, 000/¦ÌL, hemoglobin more than and equal to 9 gm/dL, serum bilirubin less than and equal to 1.5 times theinstitutional upper limit of normal and AST (SGOT) and ALT(SGPT) less than and equal to 2.5 times the institutional upper limit of normal. |
| Biomarker: | tumor immunohistochemical expression > or =2+/4+ for KIT or PDGFRalpha |
| Biomark Analysis: | This study intended to enrich for molecular factors that potentially predict response. |
| Control Group Info: | single arm |
| Treatment Info: | Imatinib was administered orally 400 mg twice/day for 28 days/course. |
| Primary End Point: | response |
| Secondary End Point: | NA |
| Patients Number: | 7 |
| Trial Results | |
| DLT_MTD: | Grade 3 or 4 toxicities are listed in Table II. Onepatient had development of grade 4 anemia during therapyand had progression prior to initiating a second course. Ofnote, this same patient with grade 4 anemia was pretreatedwith 2 prior chemotherapy regimens |
| Objective Response Rate: | One patient with 3+/4+ PDGFR¦Á and3+/4+ KIT expression had a partial response through 8courses. 4 patients had progression after 1 cycle. Two patientswere not evaluable due to one early death and one refusingtreatment. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | One patient had development of grade 4 anemia during therapy and had progression prior to initiating a second course. Of note, this same patient with grade 4 anemia was pretreated with 2 prior chemotherapy regimens. No patient developed leukopenia or thrombocytopenia beyond grade 2. The single patient able to complete 8 courses did experience grade 3 nausea, grade 3 vomiting, and grade 3 hypokalemia during the first week of therapy but this resolved with dose reduction to 300 mg twice a day of imatinib as per protocol. The patient continued to do well such that the dose was reescalated with initiation of cycle 4 and the patient only had recurrence of nausea, vomiting, and hypokalemia that did not progress beyond grade 1. |
| Conclusions: | This study intended to enrich for molecular factors that potentially predict response. Given the poor prognosis with recurrent ESFT, further studies with other novel KIT and PDGFRalpha inhibitors are needed. |