| General information |
| Database: | DB00586 |
| Objective: | Patients with Ewing sarcoma (ES) with metastases and those who relapse fare poorly and receive therapies that carry significant toxicity. Thisphase 1/2 study was conducted to evaluate the efficacy of figitumumab in advanced ES. |
| Authors: | Juergens H, et al |
| Title: | Preliminary efficacy of the antiinsulinlike growth factor type 1 receptor antibody figitumumab in patients with refractory Ewing sarcoma. |
| Journal: | J Clin Oncol. |
| Year: | 2013 |
| PMID: | 22025154 |
| Trial Design |
| Clinical Trial Id: | NCT00560235 |
| Agent: | figitumumab
|
| Target: | Insulinlike growth factor I receptor
|
| Cancer Type: | soft tissue sarcomas |
| Cancer Subtype: | Ewing's sarcoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | amulticenter, openlabel, phaseI/phase II clinical tri |
| Key Patients Feature: | histologically confirmed diagnosis ofosseous or extraosseous ES including variants with neural differentiation (eg, peripheral neuroectodermal tumors [PNET]). In addition, the phase 1 portion of thestudyenrolledalsopatientswithrelapsed/refractoryosteosarcoma, rhabdomyosarcoma, desmoplastic small round cell tumors, and other undifferentiated sarcomas and it was limited to 10 to18yearold patients.Other key inclusion/exclusion criteria were: disease statefor which there is no known curative therapy or therapy proven to prolongsurvival with an acceptable quality of life; Eastern Cooperative OncologyGroup performance status of 0 to 2 or a Lansky play scale 50; absoluteneutrophil count 1, 000/mL without growth factor support; platelets 75, 000/mL (previous transfusion was allowed); hemoglobin 8 g/dL(previous transfusion allowed); total bilirubin 1.5 times the upper limitof normal (ULN) for age (except for Gilbert¡¯s syndrome patients); serumALT 2.5 ULN; AST 2.5 ULN; serum creatinine 1.5 ULN forage; cardiac ejection fraction 50% or shortening fraction 28%; at least1 week from prior radiotherapy provided that it was not at the only site ofmeasurable disease; fully recovered ( grade 1 as defined by the NationalCancer Institute Common Toxicity Criteria for Adverse Events, version 3.0or deemed irreversible) from the acute effects of prior systemic therapy, including 2 weeks since previous chemotherapy (8 weeks for mitomycin ornitrosoureas) and 4 weeks from prior biologic therapy; written voluntaryinformed consent (adults), parent or legal guardian consent or patientassent/parent permission for minors; no prior antiIGF1R therapy; nosymptomatic brain metastases, significant active cardiac disease, infection, insulindependent diabetes, or concurrent use of highdose steroids |
| Biomarker: | circulating free insulinlike growth factor (IGF) 1 |
| Biomark Analysis: | Importantly, patients with a pretreatment circulating free insulinlike growth factor (IGF) 1 lotheyr than 0.65 ng/mL (n = 14) had a median OS of 3.6 months, whereas those with a baseline free IGF1 more than and equal to 0.65 ng/mL (n = 84) had a median OS of 10.4 months (P < .001). |
| Control Group Info: | single arm |
| Treatment Info: | Patients with sarcoma 10 to 18 years old were enrolled in two dose escalation cohorts (20 and 30 mg/Kg intravenously every 4 weeks) in the phase 1 portion of the study. Patients with ES 10 years old or older were enrolled in the phase 2 portion of the study. |
| Primary End Point: | objective response rate (ORR) |
| Secondary End Point: | NA |
| Patients Number: | 31 |
| Trial Results |
| DLT_MTD: | Dose escalation proceeded to 30 mg/kg every 4weeks with no doselimiting toxicity identified. |
| Objective Response Rate: | Of 106evaluable patients, 15 had a partial response (ORR, 14.2%) and 25 had stable disease. Median overallsurvival was 8.9 months |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 1.9 (95% CI, 1.8 to 2.8) |
| Median OS A vs. C: | 8.9(95% CI, 7.2 to 11.1) months. patients with a pretreatment circulating free insulinlike growth factor (IGF) 1 lotheyr than 0.65 ng/mL (n 14) had a median OS of 3.6 months, whereas those with a baseline free IGF1 0.65 ng/mL (n 84) had a median OS of 10.4 months (P .001). |
| Adverse Event(agent arm): | NA |
| Conclusions: | Figitumumab had modest activity as single agent in advanced ES. A strong association bettheyen pretreatment serum IGF1 and survival benefit was identified. |