| General information |
| Database: | DB00699 |
| Objective: | The aim of this study was to determine the maximum tolerated dose (MTD) and to assess the safety, pharmacokinetics, and antitumor activity of YM155 in patients with advanced refractory solid tumors. |
| Authors: | Satoh T, et al |
| Title: | Phase I study of YM155, a novel survivin suppressant, in patients with advanced solid tumors. |
| Journal: | Clin Cancer Res. |
| Year: | 2009 |
| PMID: | 19470738 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | YM155
|
| Target: | NA
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an openlabel, singlecenter, nonrandomized, phase I doseescalation study |
| Key Patients Feature: | Eligibility criteria for patients enrolled in this study included refractory advanced solid tumors for whichno standard therapy existed; histologic or cytologic diagnosis of cancer;at least 20 y of age; life expectancy of at least 12 wk; Eastern Cooperative Oncology Group performance status of <3; and adequate hematopoietic, hepatic, and renal functions (absolute neutrophil count ofmore than and equal to 1.5 ¡Á 109/L, platelets of more than and equal to 100 ¡Á 109/L, hemoglobin of more than and equal to 9 g/dL, bilirubin within 1.5¡Á upper limit of normal, transaminases of less than and equal to 2.5¡Á upperlimit of normal, and creatinine of <1.5 ¡Á upper limit of normal).Patients must have discontinued all cancer therapies for at least 4 wkbefore study entry. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients with advanced refractory solid tumors were treated with escalating doses of YM155 administered by continuous i.v. infusion for 168 hours in 21day cycles. |
| Primary End Point: | MTD, DLTs, safety, pharmacokinetics, and antitumor activity |
| Secondary End Point: | NA |
| Patients Number: | 34 |
| Trial Results |
| DLT_MTD: | The MTD was determined to be 8.0 mg/m2/d, based on a doselimitingtoxicity of increased blood creatinine observed in 2 patients receiving 10.6 mg/m2/d.The most common adverse reactions judged to be related to YM155 were urine microalbuminpresent; fever; injectionsite phlebitis; fatigue; and decreased hemoglobin/anemia, blood albumin, and lymphocyte count |
| Objective Response Rate: | Stable disease wasachieved in nine patients. |
| 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): | The most common adverse reactions judged to be related to YM155 were urine microalbumin present; fever; injectionsite phlebitis; fatigue; and decreased hemoglobin/anemia, blood albumin, and lymphocyte count. |
| Conclusions: | YM155 was safely administered to patients with advanced refractory solid tumors by 168hour continuous i.v. infusion in 21day cycles. The MTD was determined to be 8.0 mg/m(2)d. The safety profile, plasma concentrations achieved, and antitumor activity observed merit further studies with this survivin suppressant, alone and in combination regimens. |