| General information |
| Database: | DB00570 |
| Objective: | Temsirolimus was combined with cixutumumab, a fully human IgG1 monoclonal antibody directed at the insulin growth factor1 receptor (IGF1R). |
| Authors: | Naing A, et al |
| Title: | Insulin growth factorreceptor (IGF1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with refractory Ewing's sarcoma family tumors. |
| Journal: | Clin Cancer Res. |
| Year: | 2012 |
| PMID: | 22465830 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cixutumumab
|
| Target: | Insulinlike growth factor I receptor
|
| Cancer Type: | soft tissue sarcomas |
| Cancer Subtype: | Ewing¡¯s sarcoma (EWS) desmoplastic smallround cell tumor |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Temsirolimus+cixutumumab |
| Study Type: | II dose cohorts |
| Key Patients Feature: | Eligible patients had advanced or metastatic, histologically proven malignant EWS or DSRCT. Further requirements were age 14 years or older, ECOG performancestatus of 0 or 1, and life expectancy greater than 12weeks. patients were required to have an absolute neutrophil count (ANC) 1, 500/mL, platelets 100, 000/mL, creatinine 2 the upper limit of normal (ULN), bilirubin 1.5 ULN; AST (aspartate aminotransferase)and/or ALT (alanine aminotransferase) 5 ULN.There was no limit to number of prior treatment regimens permitted and patients could have been previouslytreated with an IGF1R or an mTOR inhibitor. Treatmentwith radiotherapy (except palliative), endocrine therapy, or chemotherapy must have ceased at least 4 weeksbefore starting treatment. Patients with wellcontrolleddiabetes and hyperlipidemia were allowed. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients received cixutumumab, 6 mg/kg i.v. weekly, and temsirolimus, 25 to 37.5 mg i.v. weekly (4week cycles), with restaging after 8 weeks. |
| Primary End Point: | DLT, satety, and efficacy. |
| Secondary End Point: | NA |
| Patients Number: | 20 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Seven of 20 patients (35%) achieved stable disease (SD) for more than 5 months or complete/partial (CR/PR) responses. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 12.3 months (95%CI: 6.6 - 20+ months). |
| Adverse Event(agent arm): | The most frequent toxicities were thrombocytopenia (85%), mucositis (80%), hypercholesterolemia (75%), hypertriglyceridemia (70%), and hyperglycemia (65%) (mostly grade 1-2). |
| Conclusions: | Cixutumumab combined with temsirolimus was welltolerated and showed preliminary evidence of durable antitumor activity in heavily pretreated EWS family tumors. |